Example chemical structure of sinistrin | |
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Properties | |
(C6H10O6)n | |
Molar mass | Variable |
Good [1] | |
Solubility in ethanol | Insoluble [2] |
Pharmacology | |
V04CH01 ( WHO ) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Sinistrin is a naturally occurring sugar polymer or polysaccharide, also known as polyfructosane. It belongs to the fructan group, like inulin. As it is the case with similar substances, such as fructans or inulin, sinistrin acts as an energy storage molecule in plants.
Already in 1879 Schmiedeberg managed to isolate this carbohydrate from the bulb of the red squill (Urginea maritima). [2] [3] He named the substance ’sinistrin’, from the Latin word 'sinister' for left, according to its optical rotation activities. Sinistrin was also found in mucines of edible snails ( Helix pomatia ) by Hammarsten in 1885. [1] Today sinistrin is industrially manufactured out of the bulb of red squill by various extraction and purification steps.[ citation needed ] In 2018, the French pharmacovigilance agency withdrew sinistrin-based products from the market after some patients experienced hypersensitivity reactions including a fatal outcome. [4]
Sinistrin is an inulin-type β–D-fructan with branches on position 6. It belongs to the group of fructans and is partly counted among the fructooligosaccharides (FOS). [3] [5] Sinistrin is composed out of fructose units (97%) and glucose units (3%, approximately), building a chain of fructose molecules with a terminal glucose unit. The degree of polymerisation (dp) of sinistrin is in average at 15, the molecular weight is at 3500 Da with a range from 2000 to 6000 Da. [3] [6] The main differences between sinistrin and inulin are the higher alkali-resistance and the better water solubility (even in cold water) of sinistrin compared to inulin.
Like inulin the polymer sinistrin is not metabolized in human blood and passes the kidneys unchanged. Both, inulin and sinistrin, are therefore frequently used for the diagnosis of kidney disorders. An important measure of kidney function is the glomerular filtration rate (GFR). GFR is the volume of fluid filtered from the renal (kidney) glomerular capillaries into the Bowman's capsule per time unit. [7] To measure this parameter, a marker substance is injected into the blood stream, and its rate of excretion in urine is compared to the plasma concentration. Such a marker substance needs to be non-toxic, not endogenous in the circulation, neither reabsorbed nor secreted in the kidney, and measurable. The measurement of the sinistrin-clearance is used to exactly determine the GFR in humans. [8] [9] The assays to determine sinistrin in urine or plasma are identical to that used for inulin. However, sinistrin is often preferred to the alternative, inulin, because it is highly soluble in water and easier to handle. For the application as a renal diagnostic an aqueous solution of sinistrin is approved under the trade name „Inutest“. [10]
A carbohydrate is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 and thus with the empirical formula Cm(H2O)n, which does not mean the H has covalent bonds with O. However, not all carbohydrates conform to this precise stoichiometric definition, nor are all chemicals that do conform to this definition automatically classified as carbohydrates.
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 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.
Polysaccharides, or polycarbohydrates, are the most abundant carbohydrates found in food. They are long-chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with water (hydrolysis) using amylase enzymes as catalyst, which produces constituent sugars. They range in structure from linear to highly branched. Examples include storage polysaccharides such as starch, glycogen and galactogen and structural polysaccharides such as cellulose and chitin.
Creatinine is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body.
Cystine is the oxidized derivative of the amino acid cysteine and has the formula (SCH2CH(NH2)CO2H)2. It is a white solid that is poorly soluble in water. As a residue in proteins, cystine serves two functions: a site of redox reactions and a mechanical linkage that allows proteins to retain their three-dimensional structure.
The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure called Bowman's capsule. The renal tubule extends from the capsule. The capsule and tubule are connected and are composed of epithelial cells with a lumen. A healthy adult has 1 to 1.5 million nephrons in each kidney. Blood is filtered as it passes through three layers: the endothelial cells of the capillary wall, its basement membrane, and between the foot processes of the podocytes of the lining of the capsule. The tubule has adjacent peritubular capillaries that run between the descending and ascending portions of the tubule. As the fluid from the capsule flows down into the tubule, it is processed by the epithelial cells lining the tubule: water is reabsorbed and substances are exchanged ; first with the interstitial fluid outside the tubules, and then into the plasma in the adjacent peritubular capillaries through the endothelial cells lining that capillary. This process regulates the volume of body fluid as well as levels of many body substances. At the end of the tubule, the remaining fluid—urine—exits: it is composed of water, metabolic waste, and toxins.
Ludwig Karl Martin Leonhard Albrecht Kossel was a German biochemist and pioneer in the study of genetics. He was awarded the Nobel Prize for Physiology or Medicine in 1910 for his work in determining the chemical composition of nucleic acids, the genetic substance of biological cells.
Inulins are a group of naturally occurring polysaccharides produced by many types of plants, industrially most often extracted from chicory. The inulins belong to a class of dietary fibers known as fructans. Inulin is used by some plants as a means of storing energy and is typically found in roots or rhizomes. Most plants that synthesize and store inulin do not store other forms of carbohydrate such as starch. In the United States in 2018, the Food and Drug Administration approved inulin as a dietary fiber ingredient used to improve the nutritional value of manufactured food products. Using inulin to measure kidney function is the "gold standard" for comparison with other means of estimating glomerular filtration rate.
Uremia is the term for high levels of urea in the blood. Urea is one of the primary components of urine. It can be defined as an excess in the blood of amino acid and protein metabolism end products, such as urea and creatinine, which would be normally excreted in the urine. Uremic syndrome can be defined as the terminal clinical manifestation of kidney failure. It is the signs, symptoms and results from laboratory tests which result from inadequate excretory, regulatory, and endocrine function of the kidneys. Both uremia and uremic syndrome have been used interchangeably to denote a very high plasma urea concentration that is the result of renal failure. The former denotation will be used for the rest of the article.
Renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearing toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pressure; production of various hormones, such as erythropoietin; and activation of vitamin D.
Renal physiology is the study of the physiology of the kidney. This encompasses all functions of the kidney, including maintenance of acid-base balance; regulation of fluid balance; regulation of sodium, potassium, and other electrolytes; clearance of toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pressure; production of various hormones, such as erythropoietin; and activation of vitamin D.
Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging.
The glomerulus is a network of small blood vessels (capillaries) known as a tuft, located at the beginning of a nephron in the kidney. Each of the two kidneys contains about one million nephrons. The tuft is structurally supported by the mesangium, composed of intraglomerular mesangial cells. The blood is filtered across the capillary walls of this tuft through the glomerular filtration barrier, which yields its filtrate of water and soluble substances to a cup-like sac known as Bowman's capsule. The filtrate then enters the renal tubule of the nephron.
Mesangial cells are specialised cells in the kidney that make up the mesangium of the glomerulus. Together with the mesangial matrix, they form the vascular pole of the renal corpuscle. The mesangial cell population accounts for approximately 30-40% of the total cells in the glomerulus. Mesangial cells can be categorized as either extraglomerular mesangial cells or intraglomerular mesangial cells, based on their relative location to the glomerulus. The extraglomerular mesangial cells are found between the afferent and efferent arterioles towards the vascular pole of the glomerulus. The extraglomerular mesangial cells are adjacent to the intraglomerular mesangial cells that are located inside the glomerulus and in between the capillaries. The primary function of mesangial cells is to remove trapped residues and aggregated protein from the basement membrane thus keeping the filter free of debris. The contractile properties of mesangial cells have been shown to be insignificant in changing the filtration pressure of the glomerulus.
Podocytes are cells in Bowman's capsule in the kidneys that wrap around capillaries of the glomerulus. Podocytes make up the epithelial lining of Bowman's capsule, the third layer through which filtration of blood takes place. Bowman's capsule filters the blood, retaining large molecules such as proteins while smaller molecules such as water, salts, and sugars are filtered as the first step in the formation of urine. Although various viscera have epithelial layers, the name visceral epithelial cells usually refers specifically to podocytes, which are specialized epithelial cells that reside in the visceral layer of the capsule. One type of specialized epithelial cell is podocalyxin.
Ernst Felix Immanuel Hoppe-Seyler was a German physiologist and chemist, and the principal founder of the disciplines of biochemistry and molecular biology. He had discovered Yeast nucleic acid which is now called RNA in his attempts to follow up and confirm Miescher's results by repeating parts of Miescher's experiments
In pharmacology, clearance is a pharmacokinetic parameter representing the efficiency of drug elimination. This is the rate of elimination of a substance divided by its concentration. The parameter also indicates the theoretical volume of plasma from which a substance would be completely removed per unit time. Usually, clearance is measured in L/h or mL/min. The quantity reflects the rate of drug elimination divided by plasma concentration. Excretion, on the other hand, is a measurement of the amount of a substance removed from the body per unit time. While clearance and excretion of a substance are related, they are not the same thing. The concept of clearance was described by Thomas Addis, a graduate of the University of Edinburgh Medical School.
In the physiology of the kidney, tubuloglomerular feedback (TGF) is a feedback system inside the kidneys. Within each nephron, information from the renal tubules is signaled to the glomerulus. Tubuloglomerular feedback is one of several mechanisms the kidney uses to regulate glomerular filtration rate (GFR). It involves the concept of purinergic signaling, in which an increased distal tubular sodium chloride concentration causes a basolateral release of adenosine from the macula densa cells. This initiates a cascade of events that ultimately brings GFR to an appropriate level.
Cystatin C or cystatin 3, a protein encoded by the CST3 gene, is mainly used as a biomarker of kidney function. Recently, it has been studied for its role in predicting new-onset or deteriorating cardiovascular disease. It also seems to play a role in brain disorders involving amyloid, such as Alzheimer's disease. In humans, all cells with a nucleus produce cystatin C as a chain of 120 amino acids. It is found in virtually all tissues and body fluids. It is a potent inhibitor of lysosomal proteinases and probably one of the most important extracellular inhibitors of cysteine proteases. Cystatin C belongs to the type 2 cystatin gene family.
Kestose is a class of sugars that belongs to a group of fructooligosaccharides.