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Lecture Lesson 7. Endocrinology I
chemistry
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Clinical Chemistry 2 (MDT 3122L)
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Our Lady of Fatima University
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ENDOCRINOLOGY
- Study relates to the endocrine system, which controls the hormones
- 2 Physiologic Regulatory Systems: Endocrine system and Nervous system o These 2 are under the Neuroendocrine System o Neuroendocrinology: branch of biology which studies the interaction between the nervous system and the endocrine system o It is the idea on how the brain regulates the hormonal activity in the body
Types of Glands
➢ Endocrine: secretes substances or hormones into the bloodstream (blood in capillaries) ➢ Exocrine: gland that secretes hormone into a system of ducts that leads to the external environment
ENDOCRINE SYSTEM
- consists of ductless glands, which secrete hormone directly into the circulatory system
- they can be regulated by means of the control of hormone synthesis rather than by degradation
TYPES OF ENDOCRINE CONTROL
- Control of homeostasis
- These homeostatic control systems can be based on positive or negative feedback.
- key difference: response to the change
- they remain the constant level of the chemical composition of the extracellular and intracellular fluids Negative Feedback Positive Feedback
Negative Feedback
- more common than positive feedback
- An increase in the product, decreases the activity of the system and the production rate
- Hypothalamus stimulates the release of hormone A, which gives signals to the anterior pituitary gland to release hormone B, which gives signals to the 3 rd endocrine gland to release hormone C. Then the target cells will now respond to hormone C.
- The presence of hormone C will now signal the hypothalamus and the anterior pituitary gland to stop the stimulation since hormone C is already present
- Decrease hypothalamus activity = decrease production rate - Example: person in a cold environment o The body temperature decreases below the set point range o Negative feedback loop: causes the body to shiver and the body produces heat o It will return back to its set point range o Once it is okay, negative feedback stops
Positive Feedback
- An increase in the product, also increases the activity of the system and the production rate
- Hypothalamus stimulates the release of hormone A (GnRH), which gives signals to the anterior pituitary gland to release hormone B (FSH or LH), which gives signals to the 3 rd endocrine gland to release hormone C (estrogen). Then the target cells will now respond to hormone C.
- The presence of hormone C will send signal to continuously produce hormone B
- Positive feedback is important in the growth and development of an organism
- Pituitary Gland
- Thyroid Gland
- Parathyroid Gland
- Adrenal Gland
- Pancreas
- Reproductive Glands (ovaries and testes)
- Thymus Gland
- Pineal Gland
HORMONES
- Hormones are chemical signals produced by specialized cells secreted into the bloodstream and carried to a target tissue
- Greek word “hormon” meaning to set in motion
- Intercellular chemical signal transported to act on tissues at another site of the body to influence their activity
- Transfer information and instructions from one set of cells to another
Characteristics of hormones
- Produced by a specific endocrine gland
- Hormones are released directly from the endocrine gland to the blood circulation and carried to the site of action as a free hormone or bound to transport protein
- Acts at a specific site (target site) to induce certain characteristic and biochemical changes.
Functions of Hormones
Regulate the chemical composition and volume of the ECF
Help regulate metabolism and energy balance
Help regulate contraction of smooth and cardiac muscles and secretion of glands
Help maintain activities of immune system
Plays a role in the smooth sequential integration of growth and development
Contribute to the basic processes of reproduction, gamete production, nourishment of the fetus and embryo
Help maintain homeostasis
Methods of Hormone Delivery
➢ Endocrine: secreted in one location and release into blood circulation o Ductless glands o The hormone binds to a specific receptor to elicit physiologic response ➢ Paracrine: Secreted by endocrine cells and released into interstitial space o The hormone binds to a specific receptor in an adjacent cell and affects its function ➢ Autocrine: Secreted in endocrine cells and sometimes released into interstitial space o The hormones bind to specific receptors on cell of origin resulting to self- regulation of its function ➢ Juxtacrine: Secreted in endocrine cells and remains in relation to plasma membrane o The hormone acts on immediately adjacent cell by direct cell-to-cell contact ➢ Exocrine: Secreted in endocrine cells and released into the lumen of gut o it affects their function ➢ Neurocrine: Secreted in neurons and released into extracellular space o The hormone will bind to nearby cell and affects its function ➢ Neuroendocrine: Secreted in neurons and released from nerve endings o It interacts with receptors of cell at distant sites
Functional Types of Hormones
➢ Releasing Hormones: from hypothalamus; promote secretion of Anterior Pituitary hormones ➢ Inhibitory Hormones: from hypothalamus & GIT; suppress the secretion of a particular hormone ➢ Tropic Hormones: stimulate growth and activity of other endocrine glands ➢ Effector Hormones: secreted by all endocrine glands and w/ non endocrine cells as targets
TYPES OF HORMONES ACCORDING TO STRUCTURE
1. Steroids
- Derived from cholesterol (it is a lipid molecule precursor)
- transported to blood stream through attachment to transport protein
- Produced by: adrenal glands, ovaries, testes, and placenta
- steroids are hydrophobic (water-insoluble)
- Examples: o aldosterone o cortisol o estrogen o progesterone o testosterone o androgens Mechanism of Action Hormone Synthesis Regulation
- Free hormone is transported across cell membrane to interact with intracellular receptor
- complex binds to chromatin, producing mRNA
- mRNA initiates production of proteins that carry out the function attributed to the specific hormone
- Negative Feedback
2. Biogenic Amines (AA)
- They are derived from amino acids
- They are intermediary between steroids and proteins.
- Example: Tyrosine o Thyroid hormones ▪ T3 (triiodothyronine) ▪ T4 (thyroxine) o Adrenal hormones ▪ Epinephrine ▪ Norepinephrine/Cathecholamines Mechanism of Action Hormone Synthesis Regulation
- Epinephrine and norepinephrine do not bind to carrier proteins, instead, they interact with the receptor site on the cell membrane.
- Thyroxine and triiodothyronine circulate bound to carrier proteins, with the free hormone being transported across the cell membrane to interact with the intracellular receptor.
- Nerve stimulation
- Another hormone (e., thyroxine/TSH)
- Negative feedback
3. Peptides and Proteins
- These are hormones that are synthesized and stored within the cell in the form of secretory granules
- They are cleaved as needed.
- Synthesized by rough ER
- They cannot cross the cell membrane due to their large molecular size. Thus, they only produce their effects on the outer surface of the cell
- Water soluble and not bound to carrier protein
- hypothalamic releasing and inhibiting hormone
- Examples: o oxytocin o ADH o insulin o glucagon o GH o calcitonin o PTH Mechanism of Action Hormone Synthesis Regulation
- Hormones interact with a cell membrane receptor. This activates a second messenger system to affect the cellular function.
- Change in the analyte
- Negative Feedback
4. Glycoproteins
- Amino Acid derivatives with CHO groups
- Examples: o TSH o FSH o LH
Open-Loop Negative Feedback System
- Relationship of hormones produced by hypothalamus and pituitary gland
- they are subject to external modulation and generally influenced or modified by higher neural input or other hormones.
- This type of axis can be partially inhibited by adrenal steroids and also cytokines. As a result, thyroid hormone production may decline during periods of severe physiologic stress
2. Pulsatile Secretion
- a biochemical phenomenon in which chemical is secreted in a burst-like or episodic manner rather than constantly
- Examples: o GnRH: median interpulse interval is 90 to 120 mins. o LH: ▪ median interpulse interval is 55 minutes ▪ average peak duration is 40 minutes
3. Cyclic Nature of Hormone Secretion
- The nervous system usually regulates this function through external signals, such as light- dark changes or the ratio of daylight to darkness.
- Zeitgeber (“time giver”): process of entraining or synchronizing these external cues into the function of internal biologic clocks
- pituitary hormones are secreted in different amounts, depending on the time of day.
- Example: ACTH o lowest level of secretion: 11PM-3AM o Peak secretion: 6 AM-9AM
PITUITARY HORMONES
➢ Tropic Hormones: actions are specific for another endocrine gland o TSH: directs the thyroid production from the thyroid o LH: directs testosterone production from Leydig cells in men while it directs ovulation in women o FSH: responsible for ovarian recruitment in early folliculogenesis in women, and early spermatogenesis in men o ACTH: regulates the adrenal steroidogenesis ➢ Direct Effectors: act directly on peripheral tissue o GH o Prolactin
TWO LOBES OF PITUITARY GLAND
1. Anterior Pituitary Gland
- Also called as adenohypophysis or the true endocrine gland
- Composed of three cell types: o Chromophobe (50%) o Acidophilic (40%) o Basophilic (10%)
- regulate the release & production of hormones
- Hormones secreted are either peptides or glycoproteins Examples: - GH, PRL, TSH, FSH, LH, ACTH (regulates the activity of thyroid, adrenals, and reproductive glands) - also secretes endorphins (acts on the nervous system and reduce feelings of pain) Adenohypophysis Hormones
1. Growth Hormone (Somatotrophin)
- Exert major effects in the cartilage and the growth of long bones
- GH is considered as amphibolic hormone (directly influences both catabolic and anabolic processes)
- GH also directly antagonizes the effects of insulin in glucose metabolism
- It promotes hepatic gluconeogenesis and stimulates lipolysis
- The somatotrophs comprise over 1/3 of normal pituitary weight.
- Stimulated by GHRH
- secretion is inhibited by somatostatin
- median interpulse interval is 2 to 3 hours
- peak occurring at the onset of sleep (sleeping is a stimulator of growth hormone)
- structurally related to prolactin and human placental lactogen
- GH deficiency in children may be accompanied by hypoglycemia; in adults, hypoglycemia may occur if both GH and ACTH are deficient. Factors Affecting GH Secretion Hormones that influences secretion and metabolic effects of GH: thyroxine, cortisol, estrogen, somatostatin, somatotropin releasing factor
2. Prolactin (PRL)
- A pituitary lactogenic hormone; a stress hormone; also important for parturition o Classified as a direct effector hormone because it has diffuse target tissue and lacks a single endocrine end organ
- Its amino acid structure is almost similar to GH
- Function in the initiation and maintenance of lactation
- Also acts in conjunction with estrogen and progesterone to promote breast tissue development
- Main inhibitory factor: dopamine 3 Forms of Circulating Prolactin ➢ Non-glycosylated monomer: major form ➢ Big prolactin: consists of dimeric and trimeric glycosylated form ➢ Macro-prolactin: which is less physiologically active for
Specimen consideration - Collect 3 - 4 hours after the patient awakes - Highest level: 4 - 8am and 8 - 10pm
3. Thyroid Stimulating Hormone (TSH)
- Also called as thyrotropin
- Αlpha subunit has the same amino acid sequences of LH, FSH and HCG
- ß subunit carries the specific information to the binding receptors for expression of hormonal activities
- Main stimulus for the uptake of iodide by the thyroid gland
- It acts to increase the number and size of follicular cells of follicular cells (it stimulates thyroid hormone synthesis)
4. Follicle Stimulating Hormone (FSH)
5. Luteinizing Hormone (LH)
- Gonadotropins (both FSH and LH)
- Important markers in diagnosing fertility and menstrual cycle disorder
- Present in blood in both male and female, at all ages
- FSH: growth and maturity of ovarian follicles, estrogen secretion, promotes endometrial changes, spermatogenesis o spermatogenesis for the male o early folliculogenesis for the female
- LH: ovulation and secretion of androgens and progesterone, initiates secretory phase of mens, formation of corpus luteum and development of testicular cells o Helps the Leydig cells for testosterone production for the males. o Ovulation and final follicular growth for the females
6. Adrenocorticotropic Hormone (ACTH)
- acts on the adrenal cortex to stimulate growth and secretion of corticosteroids
- follows circadian rhythm
- elevated during times of stress
- Produced in response to low serum cortisol (regulator of renal androgen synthesis)
- Deficiency of the ACTH could lead to atrophy of the zona glumerulosa and zona reticularis (these two are layers of the adrenal cortex).
- ACTH is diurnal. o Peak/Highest level: 6 - 8 am o Lowest level: 6 - 11 pm SUMMARY OF THE HORMONES OF ANTERIOR PITUITARY GLAND GH growth of bone and soft tissues PRL for lactation TSH release of thyroid hormones FSH growth of the follicle (female) and initial wave of spermatogenesis (male) LH ovulation and final follicular growth (female) and production of testosterone (male) ACTH release of cortisol
2. Posterior Pituitary Gland
- Also called as neurohypophysis
- Release of these hormones occurs in response to serum osmolality
- Hormones produced are controlled by the CNS
- Oxytocin or pitocin: for contraction of uterus and ejection of milk primed with estrogen o Synthesized in the supraoptic nuclei of the hypothalamus
- ADH or arginine vasopressin (AVP) or pitressin: permeability of kidney tubules o Synthesized in the paraventricular nuclei of the hypothalamus
1. Oxytocin
- Major effect: smooth muscle contraction
- Fergusson reflex: Stimulates contraction of the gravid uterus
- Contributes directly to uterine contractions during labor on the myometrium and promotes prostaglandin secretion
- When oxytocin is depleted, synthetic preparation of oxytocin is used to increase the weak uterine contraction during labor
- Hemostasis at the placental site after delivery
- Highest Level: 3 - 5 minutes Significance
- Useful test in some pregnant women in predicting pre-term labor
- Oat cell carcinoma of the lung and adenocarcinoma of the pancreas
2. Arginine vasopressin (AVP)
- Maintain osmotic homeostasis by regulating balance
- It is a potent agent that affects blood clotting by promoting the Factor VII release.
- Nonapeptide that acts on the DCT and collecting tubules of the kidneys
- Urine/serum /plasma osmolality and thirst may stimulate ADH secretion
- 5 - 10% drop in blood volume and blood pressure triggers (baroreceptors) the release ADH
- It increases blood pressure
- Responsible for the maintenance of blood volume, pressure, and tonicity
- Basal plasma vasopressin: 2.3-3/uL
- Diagnostic test: Overnight water deprivation test o A concentration test o After 8 - 12 hours without fluid intake, the urine osmolality should not rise above 300 mOsm/kg In Relation to Osmolality
- Principal regulator of ADH secretion: increased concentration in plasma osmolality o ADH secretion is stimulated by increased concentration in plasma osmolality
- ADH secretion is maximally stimulated at a serum osmolality of > 295 mOsm/kg and suppressed when the osmolality falls below 284 mOsm/kg
INFERTILITY
- lack of FSH and LH in both male and female
- inability to conceive after 1 year of unprotected intercourse
CUSHING’S DISEASE
- hypersecretion of ACTH
- leads to bilateral adrenal hyperplasia and cortisol overproduction
- associated with obesity
ADDISON’S DISEASE
- secondary (ACTH) or tertiary (CRH) adrenal insufficiency
- hyposecretion of glucocorticoids and aldosterone
DIABETES INSIPIDUS
- Deficient ADH
- Results in severe polyuria (≥ 3 L of urine / day)
- Clinical Pictures include: o Normoglycemia o Polyuria with low specific specific gravity o Polydypsia o Polyphagia (occasional)
True Diabetes Insipidus
- Hypothalamic/ neurogenic/ cranial/ central diabetes insipidus
- Deficiency of ADH with normal ADH receptor, due to hypothalamic or pituitary disease
- Failure of the pituitary gland to secrete ADH
- Large volume of urine is excreted (3- 20 L/day)
Nephrogenic Diabetes Insipidus
- Normal ADH with normal ADH receptor o renal resistance to ADH action
- Failure of the kidneys to respond to normal or elevated ADH levels
- Treatment: Desmopressin (dDAVP)
- Urine output: >2 L
- Diagnostic test: Water deprivation test
SYNDROME OF INAPPROPRIATE
ADH SECRETION (SIADH)
- autonomous sustained production of AVP in the absence of known stimuli for its release
- malignancy, CNS diseases, pulmonary disorders drug therapies
- decreased urine volume, increased sodium concentration and urine osmolality
- Occurs when there is uncontrolled secretion of ADH without any known stimulus for such release
- ADH is release even though the blood volume is normal or increased and plasma osmolality is low - Ectopic tumor production of ADH: small cell carcinoma of the lung - Associated with CNS and Pulmonary disease - Administration of certain drugs - Diagnosis: Water load test
HYPOPITUITARISM
- Panhypopituitarism: failure of either the pituitary or the hypothalamus results in the loss of the anterior pituitary gland function. o tumors o trauma o radiation therapy o infarction o infection o familial o idiopathic
- Monotropic hormone deficiency (loss of only a single pituitary hormone)
- Treatment: replacement therapy o Patients are treated with thyroxine, glucocorticoids, and gender-specific sex steroids
LABORATORY MEASUREMENT OF SOME
ELISA
Sandwich ELISA Indirect ELISA
- Capture Ab
- Assay diluent
- Std. &
- Samples
- Detection Ab
- Avidin-HRP
- Substrate Stop solution
- Read absorbance at 450 nm
- Antigen coating
- Diluted samples Detection Ab
- Enzyme
- Substrate
- Read absorbance at 405 nm
Sandwich ELISA
- measures antigen between two layers of antibodies (capture and detection antibodies)
- The target antigen must contain at least 2 antigenic sites capable of binding to the antibodies.
- Monoclonal or polyclonal antibodies can be used for capture and detection antibodies.
- can be read at 450 nm.
Indirect ELISA
A two-step ELISA
It involves the binding processes of primary antibody and labeled secondary antibody.
The primary antibody is incubated with the antigen followed by the incubation with the secondary antibody.
can be read at 405 nm.
GROWTH HORMONE IMMUNOASSAY
- uses specific GH antibody
- require multiple measurements o draw specimens every 20 - 30 minutes over a 12 - 24 hours period
- Insulin tolerance test: to produce hypoglycemia and provoke GH release o Basal: 2 - 5 ng/mL or ug/L o Insulin tolerance: >10 ng/mL o Arginine/L-dopa: >7 ng/mL 71
hGH-EASIA
- solid phase Enzyme Amplified Sensitivity Immunoassay
- Mab 1-hGH-Mab-HRP
- For the quantitative determination of human GH in human serum and plasma.
- Principle: a solid phase enzyme amplified sensitivity immunoassay performed in microtiter plates. The standards or samples containing the hGH react with the captured monoclonal antibodies mABS- 1 coated on a plastic well and mABS- 2 labeled with horseradish peroxidase
- absorbance is measured after colorimetric reaction o Day: <0-10 uIU/mL o Night: 30 uIU/mL
PROLACTIN IMMUNOASSAY
- homologous competitive binding immunoassay/ sandwich technique
- uses two or more antibodies directed at different parts of the PRL molecule
- hook effect: there are excessive amounts of analyte, like prolactin, in a one-step immunoassay. The excess analyte overwhelms the capture antibody, and this will allow the excess analyte to bind with the detection antibodies directly. Hence, this will prevent the formation of Ag-Ab sandwich o Adult male: 3 - 14 ng/mL or ug/L o Adult female: 3-23 ng/mL or ug/ o Pregnancy, 3rd tri: 95 - 473 ng/mL
ACTH IMMUNOASSAY
- chemiluminescence and ELISA
- related test: cortisol
- reacts with intact ACTH and ACTH fragments o Adults: 5 - 80 pg/mL (x 0 = pmol/L) o Specimen: Plasma (EDTA)
DYNAMIC FUNCTION TEST
- stimulating or suppressing a particular hormonal axis, and observing the appropriate hormonal response o If excess is suspected, conduct a suppression test o If deficiency is suspected, conduct a stimulation test
- Stimulus: exogenous analogue of a trophic hormone or a biochemical or physiological stress like hypoglycemia or exercise
INSULIN STRESS TEST
- done when hypopituitarism is suspected
- also known as Insulin Tolerance Test
- insulin is administered to produce hypoglycemic stress (<2 mmol/L)
- Tests the ability of Anterior Pituitary Gland to produce ACTH and GH o GH: >6 ug/L o Cortisol: > 500 nmol/L
TRH TEST
- assesses the adequacy of Anterior Pituitary Reserve, or to evaluate hypothalamic disease (TSH response to TRH is delayed: TSH higher at 60 minutes than 20 minutes) o Hyperthyroidism: pituitary response to TRH is flat (TSH < 2mU/L) o Hypothyroidism: exaggerated response (>25 mU/L)
- TRH is given as an IV bolus or IV push (rapid injection of the medication)
- Blood sampling done at 0, 20, and 60 minutes
- TRH is a stimulation test and a diagnostic test
GnRH TEST
- assesses hypogonadism
- can be done together with anterior pituitary function test (IST, TRH, GnRH tests)
- Normally, o Adults: GnRH causes marked rise in LH (increments of >15 U/L) and smaller rise in FSH (>2 U/L) o Children: GnRH causes marked rise in FSH and smaller rise in LH Normal response in combined PG function test
ACTH STIMULATION TEST
- cosyntropin test or tetracosactide test
- small amount of synthetic ACTH is injected, and amount of cortisol or aldosterone is measured
- distinguish whether the cause is adrenal (low cortisol and aldosterone production) or pituitary (low ACTH production) o cortisol should be increased by twofold to threefold within 60 minutes o fasting (8 hrs)
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Lecture Lesson 7. Endocrinology I
Course: Clinical Chemistry 2 (MDT 3122L)
165 Documents
Students shared 165 documents in this course
University: Our Lady of Fatima University
Was this document helpful?
CLINICAL CHEMISTRY 2 (LECTURE)
ENDOCRINOLOGY
- Study relates to the endocrine system, which
controls the hormones
- 2 Physiologic Regulatory Systems: Endocrine
system and Nervous system
o These 2 are under the Neuroendocrine
System
o Neuroendocrinology: branch of biology
which studies the interaction between
the nervous system and the endocrine
system
o It is the idea on how the brain regulates
the hormonal activity in the body
Types of Glands
➢ Endocrine: secretes substances or hormones
into the bloodstream (blood in capillaries)
➢ Exocrine: gland that secretes hormone into a
system of ducts that leads to the external
environment
ENDOCRINE SYSTEM
- consists of ductless glands, which secrete
hormone directly into the circulatory system
- they can be regulated by means of the control of
hormone synthesis rather than by degradation
TYPES OF ENDOCRINE CONTROL
- Control of homeostasis
- These homeostatic control systems can be based
on positive or negative feedback.
- key difference: response to the change
- they remain the constant level of the chemical
composition of the extracellular and intracellular
fluids
Negative Feedback Positive Feedback
Negative Feedback
- more common than positive feedback
- An increase in the product, decreases the
activity of the system and the production rate
- Hypothalamus stimulates the release of
hormone A, which gives signals to the anterior
pituitary gland to release hormone B, which
gives signals to the 3rd endocrine gland to
release hormone C. Then the target cells will
now respond to hormone C.
- The presence of hormone C will now signal the
hypothalamus and the anterior pituitary gland to
stop the stimulation since hormone C is already
present
- Decrease hypothalamus activity = decrease
production rate
- Example: person in a cold environment
o The body temperature decreases below
the set point range
o Negative feedback loop: causes the body
to shiver and the body produces heat
o It will return back to its set point range
o Once it is okay, negative feedback stops
Positive Feedback
- An increase in the product, also increases the
activity of the system and the production rate
- Hypothalamus stimulates the release of
hormone A (GnRH), which gives signals to the
anterior pituitary gland to release hormone B
(FSH or LH), which gives signals to the 3rd
endocrine gland to release hormone C
(estrogen). Then the target cells will now
respond to hormone C.
- The presence of hormone C will send signal to
continuously produce hormone B
- Positive feedback is important in the growth and
development of an organism
• Pituitary Gland
• Thyroid Gland
• Parathyroid
Gland
• Adrenal Gland
• Pancreas
• Reproductive
Glands (ovaries
and testes)
• Thymus Gland
• Pineal Gland
HORMONES
- Hormones are chemical signals produced by
specialized cells secreted into the bloodstream
and carried to a target tissue
- Greek word “hormon” meaning to set in motion
- Intercellular chemical signal transported to act
on tissues at another site of the body to
influence their activity
- Transfer information and instructions from one
set of cells to another
Characteristics of hormones
- Produced by a specific endocrine gland
- Hormones are released directly from the
endocrine gland to the blood circulation and
carried to the site of action as a free hormone or
bound to transport protein
- Acts at a specific site (target site) to induce
certain characteristic and biochemical changes.
Functions of Hormones
• Regulate the chemical composition and volume
of the ECF
• Help regulate metabolism and energy balance
• Help regulate contraction of smooth and cardiac
muscles and secretion of glands
• Help maintain activities of immune system
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