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Movements, leaders, victories and the continuing fight for equality.
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In 1968 Shirley Chisholm became the first Black woman elected to the United States Congress. In 1972 she launched a campaign for the Democratic presidential nomination, breaking another political barrier.
MORE →Reflects the personal views, recollections, and perspective of the author, Mike Davis.
This is a personal recollection on the Move fire on May 13, 1985
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| Pronunciation | US: /ˌkælsɪˈtraɪɒl/;[1][2][3][4][5] UK: /kælˈsɪtriɒl/ |
| Trade names | Rocaltrol, Calcijex, Decostriol, others |
| Other names | 1,25-dihydroxycholecalciferol, 1alpha,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D3, cholecalcitriol, 1α,25-(OH)2D3, 1,25(OH)2D3[6] |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682335 |
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| Routes of administration | By mouth, intravenous[7] |
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| Protein binding | 99.9% |
| Metabolism | Kidney |
| Elimination half-life | 5–8 hours (adults), 27 hours (children) |
| Excretion | Faeces (50%), urine (16%) |
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.046.315 |
| Chemical and physical data | |
| Formula | C27H44O3 |
| Molar mass | 416.646 g·mol−1 |
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Calcitriol is a hormone and the active form of vitamin D3, normally made in the kidney.[8][9][10] It is also known as or 1,25-dihydroxycholecalciferol (1,25-(OH)2D3). It binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the expression of many genes.[11] Calcitriol increases blood calcium mainly by increasing the uptake of calcium from the intestines.[7]
Calcitriol can be given as a medication for the treatment of osteoporosis, osteomalacia, familial hypophosphatemia, low blood calcium due to hypoparathyroidism, and low blood calcium and hyperparathyroidism due to kidney disease.[7][12] It can be taken by mouth or by injection into a vein.[7] Excessive amounts or intake can result in weakness, headache, nausea, constipation, urinary tract infections, and abdominal pain.[7][12] Serious side effects may include high blood calcium and anaphylaxis.[7]
Calcitriol was identified as the active form of vitamin D3 in 1971 and the drug was approved for medical use in the United States in 1978.[7] It is available as a generic medication.[12] In 2023, it was the 249th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[13][14] It is on the World Health Organization's List of Essential Medicines.[15]
Calcitriol is prescribed for:[16]
Calcitriol has been used in an ointment for the treatment of psoriasis,[17] although the vitamin D analogue calcipotriol (calcipotriene) is more commonly used.[18] Calcitriol has also been given by mouth for the treatment of psoriasis[19] and psoriatic arthritis.[20] Research on the noncalcemic actions of calcitriol and other VDR-ligand analogs and their possible therapeutic applications has been reviewed.[21]
The main adverse drug reaction associated with calcitriol therapy is hypercalcaemia – early symptoms include: nausea, vomiting, constipation, anorexia, apathy, headache, thirst, pruritus, sweating, and/or polyuria. Compared to other vitamin D compounds in clinical use (cholecalciferol, ergocalciferol), calcitriol has a higher risk of inducing hypercalcemia. However, such episodes may be shorter and easier to treat due to its relatively short half-life.[16]
High calcitriol levels may also be seen in human disease states in patients not on supplementation. In someone with hypercalcaemia and high calcitriol levels, low intact parathyroid hormone levels are usually present.
The major conditions with hypercalcaemia due to elevated calcitriol levels are lymphoma, tuberculosis and sarcoidosis where excess production occurs due to ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages.[22] Other conditions producing similar findings including:
Some plants contain glycosides of 1,25-dihydroxycholecalciferol. Consumption of these glycosides by grazing animals leads to vitamin D toxicity, resulting in calcinosis, the deposition of excessive calcium in soft tissues. Three rangeland plants, Cestrum diurnum, Solanum malacoxylon, and Trisetum flavescens, are known to contain these glycosides. Of these, only C. diurnum is found in the U.S., mainly in Florida.[23]
Calcitriol increases blood calcium levels ([Ca2+
]) by:
Calcitriol acts in concert with parathyroid hormone (PTH) in all three of these roles. For instance, PTH also indirectly stimulates osteoclasts. However, the main effect of PTH is to increase the rate at which the kidneys excrete inorganic phosphate (Pi), the counterion of Ca2+
. The resulting decrease in serum phosphate causes hydroxyapatite (Ca5(PO4)3OH) to dissolve out of bone, thus increasing serum calcium. PTH also stimulates the production of calcitriol (see below).[25]
Many of the effects of calcitriol are mediated by its interaction with the calcitriol receptor, also called the vitamin D receptor or VDR.[26] For instance, the unbound inactive form of the calcitriol receptor in intestinal epithelial cells resides in the cytoplasm. When calcitriol binds to the receptor, the ligand-receptor complex translocates to the cell nucleus, where it acts as a transcription factor promoting the expression of a gene encoding a calcium binding protein. The levels of the calcium binding protein increase enabling the cells to actively transport more calcium (Ca2+
) from the intestine across the intestinal mucosa into the blood.[25] Alternative, non-genomic pathways may be mediated through either PDIA3 or VDR.[27]
The maintenance of electroneutrality requires that the transport of Ca2+
ions catalyzed by the intestinal epithelial cells be accompanied by counterions, primarily inorganic phosphate. Thus calcitriol also stimulates the intestinal absorption of phosphate.[25]
The observation that calcitriol stimulates the release of calcium from bone seems contradictory, given that sufficient levels of serum calcitriol generally prevent overall loss of calcium from bone. It is believed that the increased levels of serum calcium resulting from calcitriol-stimulated intestinal uptake causes bone to take up more calcium than it loses by hormonal stimulation of osteoclasts.[25] Only when there are conditions, such as dietary calcium deficiency or defects in intestinal transport, which result in a reduction of serum calcium does an overall loss of calcium from bone occur.
Calcitriol also inhibits the release of calcitonin,[28] a hormone which reduces blood calcium primarily by inhibiting calcium release from bone.[25]
Calcitriol is produced in the cells of the proximal tubule of the nephron in the kidneys by the action of 25-Hydroxyvitamin D 1-alpha-hydroxylase, a mitochondrial oxygenase and an enzyme which catalyzes the hydroxylation of calcifediol (25-hydroxycholecalciferol, 25-OH D3) in the 1-alpha position.
The activity of this enzyme is stimulated by PTH. This is an important control point in Ca2+ homeostasis.[25] Additional effects on the production of calcitriol include an increase by prolactin, a hormone which stimulates lactogenesis (the formation of milk in mammary glands), a process which requires large amounts of calcium.[29] Activity is also decreased by high levels of serum phosphate and by an increase in the production of the hormone FGF23 by osteocyte cells in bone.[30]
Calcitriol is also produced outside the kidney in small amounts by many other tissues including placenta and activated macrophages.[31]
Analogous to the conversion of D3 to 25-OH D3 and then to calcitriol, ergocalciferol (vitamin D2) is converted to 25-OH D2 (ercalcidiol) and then to 1,25-(OH)2D2 (ercalcitriol or ergocalcitriol), a product with similar effects.[32]
When the drug alfacalcidol is used, 25-hydroxylation in the liver produces calcitriol as the active metabolite. This will produce greater effects than other vitamin D precursors in patients with kidney disease who have loss of the renal 1-alpha-hydroxylase.[33]
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
The half-life of calcitriol in the body has been reported as being between 3.5 hours[34] and 12–21 hours,[35] which is much shorter than that of its precursor calcifediol, whose half-life ranges have been estimated to range from about 15 days[36] and 21 days[37] to up to 149 days and 199 days.[38] Calcitriol is inactivated by further hydroxylation to form 1,24,25-trihydroxyvitamin D, calcitroic acid. This occurs through the action of the CYP24A1 24-hydroxylase.[39] Calcitroic acid is more soluble in water and is excreted in bile and urine.
Calcitriol was first identified in 1971 by Michael F. Holick working in the laboratory of Hector DeLuca,[40][41] and also by Tony Norman and colleagues.[42]
Calcitriol was approved for medical use in the United States in 1978.[7]
Calcitriol refers specifically to 1,25-dihydroxycholecalciferol. Because cholecalciferol already has one hydroxyl group, only two (1,25) are further specified in this nomenclature, but in fact there are three (1,3,25-triol), as indicated by the name calcitriol. The 1-hydroxy group is in the alpha position, and this may be specified in the name, for instance in the abbreviation 1α,25-(OH)2D3.[6] It is also known as cholecalcitriol to emphasize its derivation from vitamin D3.[32]
Calcitriol is, strictly, the 1-hydroxylation product of calcifediol (25-OH vitamin D3), derived from cholecalciferol (vitamin D3), rather than the product of hydroxylations of ergocalciferol (vitamin D2).[6] 1α,25-Dihydroxyergocalciferol (ercalcitriol) should be used for the vitamin D2 product.[6] However, the terminology of 1,25-dihydroxyvitamin D, or 1,25(OH)2D, is often used to refer to both types of active forms of vitamin D. Indeed, both bind to the vitamin D receptor and produce biological effects.[43] In clinical use, the differences are unlikely to have major importance.[33]
Calcitriol is marketed as a pharmaceutical for medical use under various brand names including Rocaltrol (Roche), Calcijex (Abbott), Decostriol (Mibe, Jesalis), Vectical (Galderma), and Rolsical (Sun Pharma).[citation needed]
Source: Wikipedia. Article content is retrieved live through the MediaWiki API.
Calcitriol is a hormone and the active form of vitamin D3, normally made in the kidney. It is also known as or 1,25-dihydroxycholecalciferol (1,25-(OH)2D3). It binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the expression of many genes. Calcitriol increases blood calcium mainly by increasing the uptake of calcium from the intestines. Calcitriol can be given as a medication for the treatment of osteoporosis, osteomalacia, familial hypophosphatemia, low blood calcium due to hypoparathyroidism, and low blood calcium and hyperparathyroidism due to kidney disease. It can be taken by mouth or by injection into a vein. Excessive amounts or intake can result in weakness, headache, nausea, constipation, urinary tract infections, and abdominal pain. Serious side effects may include high blood calcium and anaphylaxis. Calcitriol was identified as the active form of vitamin D3 in 1971 and the drug was approved for medical use in the United States in 1978. It is available as a generic medication. In 2023, it was the 249th most commonly prescribed medication in the United States, with more than 1 million prescriptions. It is on the World Health Organization's List of Essential Medicines.
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retroperitoneal space, and in adult humans are about 12 centimetres (4+1⁄2 inches) in length. They receive blood from the paired renal arteries; blood exits into the paired renal veins. Each kidney is attached to a ureter, a tube that carries excreted urine to the bladder. The kidney participates in the control of the volume of various body fluids, fluid osmolality, acid–base balance, various electrolyte concentrations, and removal of toxins. Filtration occurs in the glomerulus: one-fifth of the blood volume that enters the kidneys is filtered. Examples of substances reabsorbed are solute-free water, sodium, bicarbonate, glucose, and amino acids. Examples of substances secreted are hydrogen, ammonium, potassium and uric acid. The nephron is the structural and functional unit of the kidney. Each adult human kidney contains around 1 million nephrons, while a mouse kidney contains only about 12,500 nephrons. The kidneys also carry out functions independent of the nephrons. For example, they convert a precursor of vitamin D to its active form, calcitriol; and synthesize the hormones erythropoietin and renin. Chronic kidney disease (CKD) has been recognized as a leading public health problem worldwide. The global estimated prevalence of CKD is 13.4%, and patients with kidney failure needing renal replacement therapy are estimated between 5 and 7 million. Procedures used in the management of kidney disease include chemical and microscopic examination of the urine (urinalysis), measurement of kidney function by calculating the estimated glomerular filtration rate (eGFR) using the serum creatinine; and kidney biopsy and CT scan to evaluate for abnormal anatomy. Dialysis and kidney transplantation are used to treat kidney failure; one (or both sequentially) of these are almost always used when renal function drops below 15%. Nephrectomy is frequently used to cure renal cell carcinoma. Renal physiology is the study of kidney function. Nephrology is the medical specialty that addresses diseases of kidney function: these include CKD, nephritic and nephrotic syndromes, acute kidney injury, and pyelonephritis. Urology addresses diseases of kidney (and urinary tract) anatomy: these include cancer, renal cysts, kidney stones and ureteral stones, and urinary tract obstruction. The word "renal" is an adjective meaning "relating to the kidneys", and its roots are French or late Latin. Whereas according to some opinions, "renal" should be replaced with "kidney" in scientific writings such as "kidney artery", other experts have advocated preserving the use of "renal" as appropriate including in "renal artery".
Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction of all muscle cell types, and in fertilization. Many enzymes require calcium ions as a cofactor, including several of the coagulation factors. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation. Plasma calcium levels in mammals are tightly regulated, with bone acting as the major mineral storage site. Calcium ions, Ca2+, are released from bone into the bloodstream under controlled conditions. Calcium is transported through the bloodstream as dissolved ions or bound to proteins such as serum albumin. Parathyroid hormone secreted by the parathyroid gland regulates the resorption of Ca2+ from bone, reabsorption in the kidney back into circulation, and increases in the activation of vitamin D3 to calcitriol. Calcitriol, the active form of vitamin D3, promotes absorption of calcium from the intestines and bones. Calcitriol also plays a key role in upregulating levels of intracellular calcium, and high levels of this ion appear to be protective against cancers of the breast and prostate. The suppression of calcitriol by excessive dietary calcium is believed to be the major mechanism for the potential link between dairy and cancer. However, the vitamin D present in many dairy products may help compensate for this deleterious effect of high-calcium diets by increasing serum calcitriol levels. Calcitonin secreted from the parafollicular cells of the thyroid gland also affects calcium levels by opposing parathyroid hormone; however, its physiological significance in humans is in dispute. Intracellular calcium is stored in organelles which repetitively release and then reaccumulate Ca2+ ions in response to specific cellular events: storage sites include mitochondria and the endoplasmic reticulum. Characteristic concentrations of calcium in model organisms are: in E. coli 3 mM (bound), 100 nM (free), in budding yeast 2 mM (bound), in mammalian cell 10–100 nM (free) and in blood plasma 2 mM.
Parathyroid hormone (PTH), also known as parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands. It plays a critical role in regulating serum calcium and phosphate levels through its actions on bone, kidneys, and the small intestine. PTH increases serum calcium levels and is opposed by calcitonin. It also promotes the synthesis of calcitriol, the active form of vitamin D. PTH is secreted in response to low blood serum calcium (Ca2+) levels and is a key regulator of bone remodeling, the continuous process of bone resorption and formation. PTH indirectly stimulates osteoclast activity, promoting the release of calcium from the bone matrix to restore serum calcium levels. The bones serve as a reservoir of calcium, releasing it as needed to maintain homeostasis in the face of fluctuating metabolism, stress, and nutritional status. Produced primarily by the chief cells of the parathyroid glands, PTH is a polypeptide prohormone (precursor to a hormone) consisting of 84 amino acids and has a molecular mass of approximately 9500 Da. Its gene is located on chromosome 11 in humans. PTH exerts its biological effects via two main receptors. The Parathyroid hormone 1 receptor, activated by the 34 N-terminal amino acids of PTH, is highly expressed in bone and kidney cells. The Parathyroid hormone 2 receptor is predominantly found in the central nervous system, pancreas, testes, and placenta. The hormone has a short half-life of approximately 4 minutes. Dysregulation of PTH secretion, as seen in conditions like hypoparathyroidism, hyperparathyroidism, and paraneoplastic syndromes, can result in bone disease, hypocalcemia, or hypercalcemia.
Before the 1921 destruction of Tulsa’s Greenwood District, Black residents had created a remarkable center of business and community life. The district included stores, professional offices, entertainment venues and homes owned by Black citizens. Understanding Greenwood means learning what was built—not only what was burned.
MORE →Mae Jemison, aboard Space Shuttle Endeavour in 1992.
