Parathyroid Glands Introduction
- In human beings, normally there are four parathyroid glands, which are located immediately behind the thyroid gland at the upper and lower poles.
- The parathyroid glands are very small glands measuring about 6 mm long, 3 mm wide, and 2 mm thick with dark brown color.
Parathyroid Glands Histology: Each parathyroid gland is made up of chief cells and oxyphil cells. The chief cells secrete parathormone. The function of the oxyphil cell is not known.
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- It is believed that oxyphil cells are the degenerated chief cells. However, these cells may secrete parathormone during a pathological condition, parathyroid adenoma. The number of oxyphil cells increases after puberty.
- Parathormone secreted by the parathyroid gland is essential for the maintenance of blood calcium levels within a very narrow critical level. Maintenance of blood calcium level is necessary because calcium is an important inorganic ion for many physiological functions.
Read And Learn More: Medical Physiology Notes
Parathormone
- Source of Secretion: Parathormone (PTH) is secreted by the chief cells of the parathyroid glands.
- Chemistry: Parathormone is a protein in nature having 84 amino acids. Its molecular weight is 9500.
- Half-life and Plasma Level: Parathormone has a half-life of 10 minutes. The normal plasma level of PTH is about 1.5 to 5.5 ng/dL.
- Metabolism: Sixty to seventy percent of PTH is degraded by Kupffer cells of the liver by means of proteolysis. Degradation of
about 20-30% of PTH occurs in kidneys and to a lesser extent in other organs.
Synthesis Of Parathormone
- PTH is synthesized from the precursor called pre-pro-PTH containing 115 amino acids. First, the prepro-PTH enters the endoplasmic reticulum of the chief cells of parathyroid glands.
- There it is converted into a prohormone called pro-PTH, which contains 96 amino acids. Pro-PTH enters the Golgi apparatus where it is converted into PTH.
Actions Of Parathormone: PTH maintains the blood calcium level. It also controls the blood phosphate level.
- On Blood Calcium Level: The primary action of PTH is to maintain the blood calcium level within the critical range of 9 to 11 mg/dL. The blood calcium level has to be maintained critically because it is very important for many of the activities in the body. PTH maintains the blood calcium level by acting on bones, kidneys, and the GI tract.
- PTH increases:
- Resorption of calcium from the bones
- Absorption of calcium from renal tubules
- Absorption of calcium from the GL tract.
- PTH increases:
- On Blood Phosphate Level: PTH decreases the blood level of phosphate. It stimulates the resorption of phosphate from bone and increases its urinary excretion. It also increases the absorption of phosphate from the gastrointestinal tract through calcitriol.
- On Bone: PTH stimulates osteoclastic activity in the bone. It enhances the resorption of calcium from the bones by stimulating both osteoblasts and osteoclasts of the bone. The resorption of calcium from bones occurs in two phases:
- Rapid phase
- Slow phase.
- Rapid phase
- It occurs within minutes after the release of PTH from parathyroid glands. Immediately after reaching the bone, PTH gets attached to the receptors on the cell membrane of osteoblasts and osteocytes.
- The hormone-receptor complex increases the permeability of the membranes of these cells for calcium ions. It accelerates the calcium pump mechanism so that calcium ions move from these bone cells into the blood at a faster rate.
- Slow phase
- The slow phase of calcium resorption from bone is by the activation of osteoclasts. The osteoclasts are large, phagocytic multinucleated cells derived from monocytes or the monocyte-like cells present in the bone marrow.
- When the osteoclasts are activated by PTH, some proteolytic enzymes are released from the lysosomes of these cells. Apart from the proteolytic enzymes, several acids such as citric acid and lactic acid are also released.
- All these substances digest or dissolve the organic matrix of the bone, releasing calcium ions. The calcium ions slowly move into the plasma. Thus, PTH releases calcium from bone by activating the osteoclasts.
- Along with calcium resorption, PTH also increases phosphate absorption from the bones.
- Rapid phase
- On the Kidneys
- Calcium
- A large quantity of calcium is filtered in renal glomeruli. About 98-99% of filtered calcium is reabsorbed in renal tubules. Out of this, 60% is reabsorbed in proximal convoluted tubules and the rest in ascending limb and distal convoluted tubules.
- PTH increases the reabsorption of calcium from the renal tubules along with magnesium ions and hydrogen ions. It influences calcium reabsorption mainly from the distal convoluted tubule and proximal part of the collecting duct.
- Phosphate – Phosphaturic action: Phosphaturic action is the effect of PTH by which it influences phosphate excretion through urine. 85 – 90% of phosphate filtered in the glomeruli of the kidney is reabsorbed from proximal convoluted tubules. PTH inhibits the reabsorption of phosphate so that the excretion of phosphate through urine increases.
- Formation of 1,25-dihydroxycholecalciferol (calcitriol): PTH also increases the formation of 1,25-dihydroxy chole- calciferol (activated form of vitamin D) from 25-hydroxycholecalciferol in kidneys.
- Calcium
- On Gastrointestinal Tract
- PTH increases the absorption of calcium ions from the Gl tract indirectly. It increases the formation of 1, 25- dihydroxycholecalciferol in the kidneys. This vitamin in turn increases the absorption of calcium as well as phosphate from Gl tract.
- Thus activated vitamin D is very essential for the absorption of calcium from the Gl tract. And, PTH is essential for the formation of activated vitamin D.
- On Bone: PTH stimulates osteoclastic activity in the bone. It enhances the resorption of calcium from the bones by stimulating both osteoblasts and osteoclasts of the bone. The resorption of calcium from bones occurs in two phases:
- Role of PTH in the Activation of Vitamin D:
- Vitamin D is essential for calcium absorption from the GI tract. Sut vitamin D itself is not an active substance.
- Instead, vitamin D has to be converted into 1, 25-dihydroxycholecalciferol in the liver and kidney by various reactions. The 1,25-dihydroxycholecalciferol is the active product.
- Activation of Vitamin D
- There are various forms of vitamin D. But, the most important one is vitamin D3. It is also known as cholecalciferol. Vitamin D3 is synthesized in the skin from 7 dehydrocholesterol by the action of ultraviolet rays from the sunlight. It is also obtained from dietary sources. The activation of vitamin D3 occurs in two steps.
- First step: Cholecalciferol (vitamin D3) is converted into 25-hydroxycholecalciferol in the liver. This process is limited and is inhibited by 25-hydroxycholecalciferol itself by a feedback mechanism. This inhibition is essential for two reasons:
- Regulation of the amount of active vitamin D
- Storage of vitamin D for months together.
- If vitamin D3 is converted into 25-hydroxycholecalciferol, it remains in the body only for 2 to 5 days. But vitamin D3 is stored in the liver for several months.
- Second step: 25-hydroxycholecalciferol is converted into 1,25-dihydroxy- cholecalciferol (calcitriol) in the kidney. And, it is the active form of vitamin D3. This step needs the presence of PTH.
- First step: Cholecalciferol (vitamin D3) is converted into 25-hydroxycholecalciferol in the liver. This process is limited and is inhibited by 25-hydroxycholecalciferol itself by a feedback mechanism. This inhibition is essential for two reasons:
- There are various forms of vitamin D. But, the most important one is vitamin D3. It is also known as cholecalciferol. Vitamin D3 is synthesized in the skin from 7 dehydrocholesterol by the action of ultraviolet rays from the sunlight. It is also obtained from dietary sources. The activation of vitamin D3 occurs in two steps.
- Role of Calcium Ion in Regulating 1, 25-Dihydroxycholecalciferol: When blood calcium level increases, it inhibits the formation of 1,25-dihydroxycholecalciferol. The mechanism involved in the inhibition of the formation of 1,25-dihydroxycholecalciferol is as follows:
- An increase in calcium ion concentration directly suppresses the conversion of 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol. This effect is very mild
- Increase in calcium ion concentration decreases the PTH secretion which in turn, suppresses the conversion of 25-hydroxycholecalciferol into 1,25- dihydroxycholecalciferol.
- This regulates the calcium ion concentration of plasma itself indirectly, i.e. when the PTH synthesis bS is inhibited, the conversion of 25-hydroxycholecalciferol sent 1.25-hydroxycholecalciferol is also inhibited.
- Lack of 1.25-dihydroxycholecalciferol, decreases the absorption of calcium ions from the intestine, from the bones, and from the renal tubules as well. This makes the calcium level in the plasma to fall back to normal.
- Actions of 1, 25-Dihydroxycholecalciferol
- It increases the absorption of calcium from the intestine by increasing the formation of calcium-binding proteins in the intestinal epithelial cells. These proteins act as carrier proteins for facilitated diffusion by which the calcium ions are transported. The proteins remain in the cells for several weeks after 1,25- dihydroxycholecalciferol has been removed from the body, thus causing a prolonged effect on calcium absorption
- It increases the synthesis of calcium-induced ATPase in the intestinal epithelium
- It increases the synthesis of alkaline phosphatase in the intestinal epithelium
- It increases the absorption of phosphate from the intestine along with calcium.
- Mode of action of PTH: On the target cells PTH binds with PTH receptor which is coupled to the G protein and forms a hormone-receptor complex. The hormone-receptor complex causes the formation of cAMP which acts as a second messenger for the hormone.
Parathyroid Glands
Regulation Of Parathormone Secretion: The blood level of calcium is the main factor regulating the secretion of PTH. Blood phosphate level also influences and regulates PTH secretion.
- Blood Level of Calcium: PTH secretion is inversely proportional to blood calcium level. An increase in blood calcium level decreases PTH secretion. The conditions when PTH secretion decreases are:
- Excess quantities of calcium in the diet
- Increased vitamin D in the diet
- Increased resorption of calcium from the bones, caused by some other factors such as bone diseases.
- On the other hand, the decrease in calcium ion concentration in the blood increases PTH secretion as in the case of rickets, pregnancy, and lactation.
- Blood Level of Phosphate: PTH secretion is directly proportional to blood phosphate. level. Whenever the blood level of phosphate ff&mas&s, it combines with iodized calcium to form calcium hydrogen phosphate. This decreases ionized calcium levels in blood which stimulates PTH secretion.
Disorders Of Parathyroid Glands
The disorders of parathyroid glands are of two types:
- Hypoparathyroidism
- Hyperparathyroidism.
- Hypoparathyroidism – Hypocalcemia: Decreased secretion of PTH is called hypoparathyroidism. It leads to hypocalcemia.
- Causes for Hypoparathyroidism
- Surgical removal of parathyroid glands (parathyroidectomy)
- Removal of parathyroid glands during surgical removal of thyroid gland (thyroidectomy)
- Autoimmune disease
- Deficiency of receptors for PTH in the target cells. In this, the PTH secretion is normal or increased but the hormone cannot act on the target cells. This condition is called pseudohypoparathyroidism.
- Hypocalcemia and Tetany: Hypoparathyroidism causes hypocalcemia (decrease in plasma calcium level) by decreasing the resorption of calcium from bones. It causes neuromuscular hyperexcitability resulting in hypocalcemic tetany. Normally, tetany occurs when the plasma calcium level falls below 6 mg/dL from its normal value of 9.4 mg/dL.
- Hypocalcemic Tetany: Tetany is an abnormal condition characterized by hyperexcitability of nerves and skeletal muscles resulting in painful muscular spasms (involuntary contraction of muscle or group of muscles), particularly in feet and hands.
- The signs and symptoms of hypocalcemic tetany:
- Hyperreflexia and convulsions: The increased neural excitability results in hyperreflexia (overactive reflex actions) and convulsive muscular contractions.
- Carpopedal spasm: Carpopedal spasm is the spasm (violent and painful muscular contraction) in hands and feet that occurs due to hypocalcemia. During the spasm, the hand shows a peculiar attitude with flexion at the wrist joint, adduction of the thumb, flexion at the metacarpophalangeal joints, and extension of interphalangeal joints.
- Laryngeal stridor: Stridor means noisy breathing. Laryngeal stridor means a loud crowing sound during inspiration which occurs mainly due to laryngospasm (involuntary contraction of laryngeal muscles). The laryngeal stridor is a common feature of hypocalcemic tetany.
- Cardiovascular changes
- Dilatation of the heart
- Prolonged duration of ST segment and QT interval in ECG
- Arrhythmias
- Hypotension
- Heart failure.
- Other features
- Decreased permeability of the cell membrane
- Dry skin with brittle nails
- Hair loss
- Grand mal, petit mal, or other seizures
- Signs of mental retardation (in children) or dementia in adults.
- When the calcium level falls below 4 mg/dL it becomes fatal. During such severe hypocalcemic conditions, tetany occurs so quickly that a person develops spasms of different groups of muscles in the body. The worst affected are the laryngeal and bronchial muscles which develop respiratory arrest resulting in death.
- The signs and symptoms of hypocalcemic tetany:
- Latent or Subclinical Tetany: Latent or subclinical tetany is the neuromuscular hyperexcitability due to hypocalcemia that develops before the onset of tetany. It is characterized by general weakness and cramps in the feet and hands. The hyperexcitability in these patients is detected by some signs, which do not appear in normal persons.
- Trousseau’s sign: It is the spasm of the hand that is developed after 3 minutes of arresting the blood flow to the lower arm and hand. The blood flow to the lower arm and hand is arrested by inflating the blood pressure cuff 20 mm Hg above the patient’s systolic pressure.
- Chvostek’s sign: Chvostek’s sign is the twitch of the facial muscles caused by a gentle tap over the facial nerve in front of the ear. It is due to the hyperirritability of the facial nerve.
- Erb sign: Hyperexcitability of the skeletal muscles even to a mild electrical stimulus is called the Erb sign. It is also called the Erb-Westphal sign.
- Causes for Hypoparathyroidism
- Hyperparathyroidism Hypercalcemia: Hypersecretion of PTH is called hyperparathyroidism. It results in hypercalcemia. Hyperparathyroidism is of three types:
- Primary hyperparathyroidism: This is due to the development of a tumor in one or more parathyroid glands. Sometimes, tumors may develop in all four glands.
- Secondary hyperparathyroidism: It is due to the physiological compensatory hypertrophy of parathyroid glands in response to hypocalcemia which occurs due to other pathological conditions such as:
- Chronic renal failure
- Vitamin D deficiency
- Rickets.
- Tertiary hyperparathyroidism: Hyperplasia (abnormal increase in the number of cells) of all the parathyroid glands that develop due to chronic secondary hyperparathyroidism is called tertiary hyperparathyroidism.
Hypercalcemia; Hypercalcemia is the increase in plasma calcium level. It occurs in hyperparathyroidism because of increased resorption of calcium from bones.
The common signs and symptoms of hypercalcemia:
- Depression of the nervous system
- Sluggishness of reflex activities
- Reduced ST segment and QT interval in ECG
- Lack of appetite
- Constipation.
Parathyroid Glands
The depressive effects of hypercalcemia are noticed when the blood calcium level increases to 12 mg/dL. The condition becomes severe at 15 mg/dL and it becomes lethal when the blood calcium level reaches 17 mg/dL.
The other effects of hypercalcemia:
- Bone diseases: Bone diseases like osteitis fibrosa cystica develop.
- Parathyroid poisoning: It is a condition characterized by severe manifestations that occur when the blood calcium level rises above 15 mg/dL. In hyperparathyroidism, the concentration of both calcium and phosphate increases leading to the formation of calcium-phosphate crystals. The concentration of phosphate also increases because the kidney cannot excrete the excess amount of phosphate resorbed from the bone.
The calcium-phosphate crystals may be deposited in the tubules of the kidneys, thyroid gland, alveoli of lungs, gastric mucosa, and in the wall of the arteries. Calcium deposition results in dysfunction of these organs. Renal stones are formed when it is deposited in the kidney.
Parathyroid Function Tests
- Measurement of blood calcium level
- Chvostek’s sign and Trousseau’s sign for hypoparathyroidism.
Calcitonin
- Source of Secretion
- Calcitonin is secreted by the parafollicular cells or clear cells (C cells) situated amongst the follicles in the thyroid gland. In lower animals, the parafollicular cells are derived from ultimobranchial glands which develop from fifth pharyngeal pouches.
- In human being the ultimobranchial glands and fifth pharyngeal pouches are rudimentary and their cells are incorporated with fourth pharyngeal pouches and distributed amongst the follicles of the thyroid gland.
- Recently calcitonin is found in the brain, prostate, and bronchial cells of the lungs. However, the physiological role of calcitonin in nonthyroid tissues is not known.
- Chemistry and Synthesis: it is a polypeptide chain with 32 amino acids. Its mole- might be about 3,400. It is synthesized from procalcitonin.
- Plasma Level and Half-life: Plasma level of calcitonin is 1-2 ng/dL. It has a half-life of 5-10 minutes.
- Metabolism: Calcitonin is degraded and excreted by the liver and kidney.
Actions Of Calcitonin
- On Blood Calcium Level: Calcitonin plays an important role in controlling the blood calcium level. It decreases the blood calcium level and thereby counteracts parathormone. Calcitonin reduces the blood calcium level by acting on bones, kidneys, and intestines.
- On bones: Calcitonin stimulates osteoblastic activity and facilitates the deposition of calcium on bones. At the same time, it suppresses the activity of osteoclasts and inhibits the resorption of calcium from bones. It inhibits even the development of new osteoclasts in bones.
- On kidney: Calcitonin increases the excretion of calcium through urine, by inhibiting the reabsorption of calcium from the renal tubules.
- On the intestine: It prevents the absorption of calcium from the intestine into the blood.
- On Blood Phosphate Level: With respect to calcium, calcitonin is an antagonist to PTH. But it has similar actions to PTH with respect to phosphate. It decreases the blood level of phosphate by acting on bones and kidneys.
- On bones: Calcitonin inhibits the resorption of phosphate from bone and stimulates the deposition of phosphate on bones.
- On the kidney: Calcitonin increases the excretion of phosphate through urine, by inhibiting the reabsorption of phosphate from the renal tubules.
Regulation Of Calcitonin Secretion: High calcium content in plasma stimulates the calcitonin secretion through a calcium receptor in parsfa&cular cells. Gastrin is also known to stimulate the release of calcitonin.
Parathyroid Glands
Calcium Metabolism
Importance Of Calcium: Calcium is essential for many activities in the body such as:
- Bone and teeth formation
- Neuronal activity
- Skeletal muscle activity
- Cardiac activity
- Smooth muscle activity
- Secretory activity of the glands
- Cell division and growth
- Coagulation of blood.
Normal value: In a normal young healthy adult, there is about 1100 g of calcium in the body. It forms about 1.5% of total body weight. Ninety-nine percent of calcium is present in the bones and teeth and the rest is present in the plasma. The normal blood calcium level ranges between 9 and 11 mg/dL.
Types Of Calcium
Calcium in Plasma: Calcium is present in three forms in plasma:
- Ionized or diffusible calcium
- Nonionized or nondiffusible calcium
- Calcium bound to albumin.
- Ionized calcium is found freely in the plasma and it forms about 50% of plasma calcium. It is essential for vital functions like neuronal activity, muscle contraction, cardiac activity, secretions in the glands, blood coagulation, etc.
- About 8-10% of plasma calcium is present in nonionic form such as calcium bicarbonate. About 40-42% of calcium is bound with plasma protein particularly, albumin.
Calcium in Bones: Calcium is constantly removed from bone and deposited in bone. Bone calcium is present in two forms.
- Rapidly exchangeable calcium
- Slowly exchangeable calcium.
The rapidly exchangeable calcium is in small quantities in bones. It is often called exchangeable calcium. It helps maintain the plasma calcium level. The slowly exchangeable calcium is available in large quantities in Tom. H is also called stable calcium. It helps in bone remodeling. The process of calcium metabolism is explained schematically.
Source Of Calcium
- Dietary Source: Calcium is available in several foodstuffs. The percentage of calcium in different food substances is:
- Whole milk = 10%
- Low fat milk = 18%
- Cheese = 27%
- Other dairy products = 17%
- Vegetables = 7%
- Other substances such as meat, egg, grains, sugar, coffee, tea, chocolate, etc. = 21%
From Bones: Besides dietary calcium, blood also gets calcium from bone by resorption.
Daily Requirements Of Calcium
1-3 years = 500 mg
4-8 years = 800 mg
9-18 years = 1300 mg
19-50 years = 1000 mg
51 years and above = 1200 mg
Pregnant ladies and lactating mothers = 1300 mg
Parathyroid Glands
Absorption And Excretion Of Calcium: Calcium taken through dietary sources is absorbed from the Gl tract into the blood and distributed to various parts of the body. Depending upon the blood level, the calcium is either deposited in the bone or removed from the bone (resorption). Calcium is excreted from the body through urine and feces.
- Absorption from Gl Tract: Calcium is absorbed from the duodenum by carrier-mediated active transport and from the rest of the small intestine by facilitated diffusion. Vitamin D is essential for the absorption of calcium from the GL tract.
- Excretion: While passing through the kidney, a large quantity of calcium is filtered in the glomerulus. From the filtrate, 98-99% of calcium is reabsorbed from renal tubules into blood. And only a small quantity is excreted through urine.
- Most of the filtered calcium is reabsorbed in the distal convoluted tubules and proximal part of the collecting duct. In distal convoluted tubule parathormone increases the reabsorption. In the collecting duct vitamin D increases the reabsorption and calcitonin decreases reabsorption.
- About 1000 mg of calcium is excreted daily. Out of this 900 mg is excreted through feces and 100 mg through urine.
Regulation Of Blood Calcium Level; Calcium metabolism is regulated mainly by three hormones:
- Parathormone
- 1,25-dihydroxycholecalciferol (calcitriol)
- Calcitonin.
1. Parathormone: It is a protein hormone secreted by the parathyroid gland and its main function is to increase the blood calcium level by mobilizing calcium from bone (resorption) (See above for details).
2. 1,25-Dihydroxycholecalciferol – Calcitriol: It is a steroid hormone synthesized in the kidney. It is the activated form of vitamin D. Its main action is to increase the blood calcium level by increasing the calcium absorption from the small intestine.
3. Calcitonin: It is a protein hormone secreted by parafollicular cells of the thyroid gland. It is a calcium-lowering hormone. If the blood calcium level mainly by decreasing
bone resorption.
Effects of Other Hormones: In addition to the above-mentioned three hormones, growth hormones, and glucocorticoids also influence the calcium level.
- Growth hormone: It increases the blood calcium level by increasing the intestinal calcium absorption. It is also suggested that it increases the urinary excretion of calcium. However, this action is only transient.
- Glucocorticoids: Glucocorticoids (cortisol) decrease blood calcium by inhibiting intestinal absorption and increasing the renal excretion of calcium.
Phosphate Metabolism
Phosphorus (P) is an essential mineral that is required by every cell in the body for normal function. Phosphorus is present in many food substances, such as peas, dried beans, nuts, milk, cheese, and butter. Inorganic phosphorus (Pi) is in the form of phosphate (PO4). The majority of the phosphorus in the body is found as phosphate. Phosphorus is also the body’s source of phosphate. In the body, phosphate is the most abundant intracellular anion.
Importance Of Phosphate
- Phosphate is an important component of many organic substances such as ATP, DNA, RNA, and many intermediates of metabolic pathways
- Along with calcium it forms an important constituent of bone and teeth
- It forms a buffer in the maintenance of acid-base balance.
Normal value: The total amount of phosphate in the body is 500-800 g. Though it is present in every cell of the body, 85-90% of the body’s phosphate is found in the bones and teeth. The normal plasma level of phosphate is 4 mg/dL.
Regulation Of Phosphate Level: Phosphorous is taken through dietary sources, it is absorbed from the Gl tract into blood and distributed to various parts of the body. While passing through the kidney, a large quantity of phosphate is excreted through urine.
Phosphate homeostasis depends upon three processes:
- Absorption from the gastrointestinal tract
- Resorption from bone
- Excretion through urine.
These three processes are regulated by three hormones:
- Parathormone
- Calcitonin
- 1,25-dihydroxycholecalciferol (calcitriol).
1. Parathormone: Parathormone stimulates the resorption of phosphate from bone, and increases its urinary excretion. It also increases the absorption of phosphate from the gastrointestinal tract through calcitriol. The overall action of parathormone decreases the plasma level of phosphate.
2. Calcitonin: Calcitonin also decreases the plasma level of phosphate by inhibiting bone resorption and stimulating urinary excretion.
3. 1,25 Dihydroxycholecalciferol- Calcitriol: This hormone increases the absorption of phosphate from the small intestine.
Effects of Giber Hormones: In addition to the above-mentioned three hormones, growth hormone, and glucocorticoids also influence the phosphate level.
- Growth hormone: It increases the blood phosphate level by increasing intestinal phosphate absorption.
- Glucocorticoids: Glucocorticoids (cortisol) decrease blood phosphate by inhibiting intestinal absorption and increasing the renal excretion of phosphate.
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