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Chondroitin
الناقل :
elmasry
| العمر :42
| الكاتب الأصلى :
محمودالراوي
| المصدر :
sayadla.com
السلام عليكم
هذا الدواء جديد نوعًا ما وإن كان استخدامه لوحده لم أجده، لأنه عادة يأتي مع Glucosamine معًا في دواء واحد
لذا حاولت أن أجد من المواقع العلمية أي معلومات تخصه لوحده وهذا ما استطعت أن أجده على عجالة
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المصدر: http://en.wikipedia.org/wiki/C hondroitin_sulfate
Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a chain of alternating sugars (N-acetylgalactosamine and glucuronic acid). It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have over 100 individual sugars, each of which can be sulfated in variable positions and quantities. Understanding the functions of such diversity in chondroitin sulfate and related glycosaminoglycans is a major goal of glycobiology. Chondroitin sulfate is an important structural component of cartilage and provides much of its resistance to compression. Along with glucosamine, chondroitin sulfate has become a widely used dietary supplement for treatment of osteoarthritis.
Terminology
Chondroitin sulfate was originally isolated well before the structure was characterised, leading to changes in terminology with time.[1] Early researchers identified different fractions of the substance with letters.
Chondroitin sulfate A is predominantly sulfated at carbon 4 of the N-acetylgalactosamine (GalNAc) sugar and is also known as chondroitin-4-sulfate. It is highly expressed in the syncytiotrophoblast, a component of the placenta. This confers susceptibility of first-time pregnant women to a strain of Plasmodium falciparum, which causes malaria.
Chondroitin sulfate B is now referred to as dermatan sulfate.
Chondroitin sulfate C is predominantly sulfated at carbon 6 of the GalNAc sugar (chondroitin-6-sulfate).
Chondroitin sulfate D is predominantly sulfated at carbon 2 of the glucuronic acid and 6 of the GalNAc sugar (chondroitin-2,6-sulfate).
Chondroitin sulfate E is predominantly sulfated at carbons 4 and 6 of the GalNAc sugar (chondroitin-4,6-sulfate).
Chondroitin, without the "sulfate", has been used to describe a fraction with little or no sulfation.[2] However, this distinction is not used by all.
Although the name "chondroitin sulfate" suggests a salt with a sulfate counter-anion, this is not the case, as sulfate is covalently attached to the sugar. Rather, since the molecule has multiple negative charges at physiological pH, a cation is present in salts of chondroitin sulfate. Commercial preparations of chondroitin sulfate typically are the sodium salt. Barnhill et al. have suggested that all such preparations of chondroitin sulfate be referred to as "sodium chondroitin" regardless of their sulfation status.[3]
Structure
Chondroitin sulfate chains are unbranched polysaccharides of variable length containing two alternating monosaccharides: D-glucuronic acid (GlcA) and N-acetyl-D-galactosamine (GalNac). Some GlcA residues are epimerized into L-iduronic acid (IdoA); the resulting disaccharide is then referred to as dermatan sulfate.
Protein attachment
Chondroitin sulfate chains are linked to hydroxyl groups on serine residues of certain proteins. Exactly how proteins are selected for attachment of glycosaminoglycans is not understood. Empirically, glycosylated serines are often followed by a glycine and have neighboring acidic residues, but this motif does not always predict glycosylation.
Attachment of the GAG chain begins with four monosaccharides in a fixed pattern: Xyl - Gal - Gal - GlcA. Each sugar is attached by a specific enzyme, allowing for multiple levels of control over GAG synthesis. Xylose begins to be attached to proteins in the endoplasmic reticulum, while the rest of the sugars are attached in the Golgi apparatus.[4]
Sulfation
Each monosaccharide may be left unsulfated, sulfated once, or sulfated twice. Most commonly the hydroxyls of the 4 and 6 positions of the N-acetyl-galactosamine are sulfated. Sulfation is mediated by specific sulfotransferases.
Function
Chondroitin's functions largely depend on the properties of the overall proteoglycan of which it is a part. These functions can be broadly divided into structural and regulatory roles. However, this division is not absolute and some proteoglycans have both structural and regulatory roles (see versican).
Structural
Chondroitin sulfate is a major component of extracellular matrix, and is important in maintaining the structural integrity of the tissue. This function is typical of the large aggregating proteoglycans: aggrecan, versican, brevican, and neurocan.
As part of aggrecan, chondroitin sulfate is a major component of cartilage. The tightly packed and highly charged sulfate groups of chondroitin sulfate generate electrostatic repulsion that provides much of the resistance of cartilage to compression. Loss of chondroitin sulfate from the cartilage is a major cause of osteoarthritis.
Regulatory
Chondroitin sulfate readily interacts with proteins in the extracellular matrix due to its negative charges. These interactions are important for regulating a diverse array of cellular activities. Although these functions are not as well characterized as those of heparan sulfate, new roles continue to be discovered for the chondroitin sulfate proteoglycans. In the nervous system, chondroitin sulfate proteoglycans regulate the growth and development of the nervous system as well as the nervous system response to injury.
Medical use
Chondroitin is an ingredient found commonly in dietary supplements used as an alternative medicine to treat osteoarthritis. It is commonly sold together with glucosamine.
Pharmacology
The dosage of oral chondroitin used in human clinical trials is 800–1,200 mg per day. Most chondroitin appears to be made from extracts of cartilaginous cow and pig tissues (cow trachea and pig ear and nose), but other sources such as shark, fish and bird cartilage are also used. Since chondroitin is not a uniform substance, and is naturally present in a wide variety of forms, the precise composition of each supplement will vary.[3] While it is a prescription or over-the-counter drug in 22 countries, chondroitin is regulated in the U.S. as a dietary supplement[1] by the Food and Drug Administration. As a result, there are no mandatory standards for formulation, and no guarantee that the product is correctly labelled. Adebowale et al. reported in 2000 that of 32 chondroitin supplements they analysed, only 5 were labeled correctly, and more than half contained less than 40% of the labeled amount.[5] However, United States Pharmacopoeia (USP) testing standards now exist for the identification and quantification of chondroitin.
Clinical studies have not identified any significant side effects or overdoses of chondroitin sulfate.
Clinical trials
Due to the popularity of the glucosamine-chondroitin supplement and the lack of reliable information about its usefulness in treating osteoarthritis,[6] the National Institutes of Health funded a study to test the effects of chondroitin and glucosamine on osteoarthritis of the knee. This multicenter, placebo-controlled, double-blind, six month long trial found that glucosamine plus chondroitin had no statistically significant effect on symptoms of osteoarthritis.[7] The control group of patients who took celecoxib (a commonly used osteoarthritis drug) did have a statistically significant improvement in their symptoms. These results indicate that glucosamine and chondroitin do not effectively relieve osteoarthiritic pain. Although the study found no overall effect for the supplements, a secondary analysis of a subgroup of patients suggested that the supplements taken together helped people with more severe pain. Studies in animals, in interesting contrast, have shown significant improvement. [2]
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Chondroitin Sulfate
TRADE NAMES
Chondroitin sulfate is available from numerous manufacturers generically. Branded products include Ramott (Key Company) Chondroitin Sulfate Support (Natural Treasures), CSA (Twinlab), Chonflex (American Health).
DESCRIPTION
Chondroitin sulfate belongs to a family of heteropolysaccharides called glycosaminoglycans or GAGs. Glycosaminoglycans were formerly known as mucopolysaccharides. GAGs in the form of proteoglycans comprise the ground substance in the extracellular matrix of connective tissue. Chondroitin sulfate is made up of linear repeating units containing D-galactosamine and D-glucuronic acid. Chondroitin sulfate is found in humans in cartilage, bone, cornea, skin and the arterial wall. This type of chondroitin sulfate is sometimes referred to as chondroitin sulfate A or galactosaminoglucuronoglycan sulfate. The amino group of galactosamines in the basic unit of chondroitin sulfate A is acetylated, yielding N-acetyl-galactosamine; there is a sulfate group esterified to the 4-position in N-acetyl-galactosamine. (Chondroitin sulfate A is also sometimes called chondroitin 4-sulfate.) The molecular weight of chondroitin sulfate ranges from 5,000 to 50,000 daltons and contains about 15 to 150 basic units of D-galactosamine and D-glucuronic acid. It is represented by the following structural formula:
Chondroitin sulfate A R = SO3H R1 = H
Chondroitin sulfate C R = H R1 = SO3H
Chondroitin sulfate C, primarily found in fish and shark cartilage, but also in humans, is also made up of linear repeating units of D-galactosamine and D-glucuronic acid. The amino group of D-galactosamine is acetylated to give N-acetyl-galactosamine, and, in the case of chondroitin sulfate C, the sulfate group is esterified to the 6-position in N-acetyl-galactosamine. Chondroitin sulfate C is sometimes called chondroitin 6-sulfate. Chondroitin sulfate B is also known as dermatan sulfate. It is abundant in skin and is also found in heart valves, tendons and arterial walls. Dermatan sulfate is made up of linear repeating units containing D-galactosamine and either L-iduronic acid or D-glucuronic acid. Its molecular weight ranges from 15,000 to 40,000 daltons.
The source of chondroitin sulfate used in nutritional supplements includes the cartilaginous rings of bovine trachea and pork byproducts (ears and snout). Shark cartilage and whale septum cartilage have also been used to obtain chondroitin sulfate. Chondroitin sulfate supplements are usually isomeric mixtures of chondroitin sulfate A(chondroitin 4-sulfate) and chondroitin sulfate C(chondroitin 6-sulfate).
ACTIONS AND PHARMACOLOGY
ACTIONS
The action of orally administered chondroitin sulfate has yet to be clarified. Possible actions include promotion and maintenance of the structure and function of cartilage (referred to as chondroprotection), pain relief of osteoarthritic joints and anti-inflammatory activity.
MECHANISM OF ACTION
Until the specific actions of supplemental chondroitin sulfate are determined, the mechanism of action is a matter of speculation. However, much is known about the biochemistry and physiology of chondroitin sulfate and similar molecules. Glycoproteins known as proteoglycans form the ground substance in the extracellular matrix of connective tissue. Proteoglycans are polyanionic substances of high molecular weight and contain heteropolysaccharide-side-chains covalently linked to a polypeptide-chain backbone. The polysaccharides, which include chondroitin sulfate and hyaluronic acid, make up as much as 95% of the proteoglycan structure.
The polysaccharides in proteoglycans are called glycosaminoglycans or GAGs. Chondroitin sulfate and hyaluronic acid are vital for the structure and function of articular cartilage. Chondroitin sulfate and hyaluronic acid are fundamental components of aggrecan found in articular cartilage. Aggrecan confers upon articular cartilage shock-absorbing properties. It does this by providing cartilage with a swelling pressure that is restrained by the tensile force of collagen fibers. This balance confers upon articular cartilage the deformable resilience vital to its function. Hyaluronic acid, which is also found in synovial fluid, has lubricating properties for the joint.
In the progression of degenerative joint disease or osteoarthritis, aggrecan synthesis is decreased, leading to the loss of cartilage resiliency and the pain and other symptoms that accompany osteoarthritis.
Intra-articular injections of hyaluronic acid, an FDA-approved drug, can relieve joint pain and improve mobility. This type of therapy is called viscotherapy and is believed to act by improving joint lubrication. If chondroitin sulfate were delivered into joints, some similar effects would be expected. Animal studies have shown that parenterally administered chondroitin sulfate does get into cartilage tissue as does orally administered chondroitin sulfate. There is some human data suggesting orally administered chondroitin sulfate, particularly low-molecular-weight chondroitin sulfate, is also delivered to articular tissue. There is some indication that orally administered chondroitin sulfate leads to increases in hyaluronic acid and viscosity of synovial fluid, as well as decreases in collagenase in synovial fluid. That is, glucosamine delivered into joints may inhibit enzymes involved in cartilage degradation and enhance the production of hyaluronic acid.
PHARMACOKINETICS
Earlier studies using high-molecular-weight chondroitin sulfate, concluded that there was no significant absorption of this high-molecular-weight version of chondroitin sulfate. More recent studies demonstrate that there is probably significant absorption of low-molecular-weight chondroitin sulfate. Absorption appears to occur from the stomach and small intestine. There is also an indication that some chondroitin sulfate, after absorption, does enter the joint space. Studies of the pharmacokinetics of orally administered chondroitin sulfate are ongoing.
It is of interest to note that a molecule similar in many resects to chondroitin sulfate, pertosan polysulfate, FDA-approved for the treatment of interstitial cystitis, is given orally and is absorbed to some extent.
INDICATIONS AND USAGE
Low-molecular-weight oral chondroitin sulfate may be indicated for the treatment and prevention of osteoarthritis, either by itself or in combination with a glucosamine supplement (see Glucosamine). There is a suggestion that chondroitin sulfate may be helpful in atherosclerosis, but more research is needed to determine if this is the case.
RESEARCH SUMMARY
Two recent -----analyses indicate that chondroitin sulfate may be useful in the treatment of osteoarthritis. One of these -----analyses included all double-blind, placebo-controlled trials that lasted four weeks or longer. This -----analysis also included trials that studied the effects of glucosamine (see Glucosamine) on osteoarthritis. In all, there were 13 of these studies (six involving glucosamine and seven involving chondroitin sulfate).
All 13 studies found positive results in hip or knee osteoarthritis. The authors of the -----analysis judged a trial positive if there was 25% or more improvement in the treatment group compared with placebo. The Levesque Index and global pain scores were used to assess improvement. Very significant improvement was associated with both glucosamine (39.5%) and chondroitin (40.2%), compared with placebo.
In another recent -----analysis of chondroitin sulfate, this one examining four randomized double-blind, placebo- or NSAID-controlled studies of 227 patients, chondroitin sulfate supplemented subjects showed at least 50% improvement, compared with controls. Various studies have reported significant reduction in NSAID use among osteoarthritis subjects supplemented with chondroitin sulfate.
There is also radiological evidence of chondroitin's possible efficacy in osteoarthritis. Knee joint space decreased significantly in placebo subjects but remained unchanged in those receiving chondroitin sulfate for a year. And, in another study, those receiving chondroitin sulfate showed significantly fewer instances of erosive osteoarthritis (compared with placebo controls) on hand radiographs over a three-year period.
A significant synergistic effect has been reported recently using combined glucosamine hydrochloride and chondroitin sulfate in an experimental study. The combination was more effective than either substance alone in inhibiting progression of degenerative cartilage lesions. Longer term clinical studies are needed to confirm or refute this synergy effect. A large multi-center study directed by the National Institutes of Health is now underway and may shed further light on this issue.
It is believed that chondroitin sulfate's possible efficacy in osteoarthritis derives from the fact that it is one of the two most abundant glycosaminoglycans (GAGs) in articular cartilage. Supplementation with this GAG seems, in part at least, to confer chondroprotection through its inhibitory action on some of the enzymes that damage cartilage. Further, by inhibiting other enzymes that can block transport of nutrients that nourish cartilage, this GAG may promote cartilage replacement.
It has been known for some time that injections of hyaluronic acid into arthritic joints can bring significant pain relief and enhanced mobility. Thus it is logical to assume that chondroitin sulfate, if it can reach the joints, may have similar effects since this substance has the ability to bind to receptor sites on synovial cell surfaces and thus induce production of hyaluronic acid, crucial to joint mobility.
The question for some time was whether a large molecule like chondroitin sulfate could achieve this penetration. Recent studies demonstrate that a low-molecular-weight version of oral chondroitin sulfate, of the sort used in all of the U.S. clinical trials, is absorbed.
Some years ago, chondroitin sulfate was investigated for its possible use in atherosclerosis. There was some evidence that it could favorably lower lipid levels and protect against blood clotting. Atheromatous aortic lesions were prevented in animals on high-cholesterol diets.
In a clinical trial, 60 patients suffering from coronary artery disease received 2 grams of oral chondroitin sulfate daily for 900 days. During that period, 16 of 60 unsupplemented control patients suffered acute coronary incidents. Only one of the chondroitin sulfate-treated subjects had an acute coronary incident. The same research group later followed up with similarly positive results.
More research is needed before any conclusions can be drawn with respect to a possible role for chondroitin sulfate in the treatment or prevention of atherosclerosis.
CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS
CONTRAINDICATIONS
None known.
PRECAUTIONS
Because of insufficient safety data, children, pregnant women and nursing mothers should avoid using chondroitin sulfate. Because of the theoretical possibility that chondroitin sulfate may have antithrombotic activity, those taking warfarin and those with hemophilia should exercise caution in its use. Those who need to restrict their salt intake should , if they use chondroitin sulfate, use salt-free preparations.
ADVERSE REACTIONS
Side effects that have been reported are mostly of the mild gastrointestinal variety, such as epigastric distress, nausea and diarrhea. No sulfa-allergic reactions or other allergic reactions have yet been reported.
INTERACTIONS
There are no known drug, nutrient, food or herb interactions. Chitosan (see Chitosan) may form complexes with chondroitin sulfate decreasing its absorption. Therefore, chondroitin sulfate should not be used concomitantly with chitosan.
OVERDOSAGE
Overdosage of chondroitin has not been reported in the literature.
DOSAGE AND ADMINISTRATION
Low-molecular-weight chondroitin sulfate is available as a stand-alone supplement or in combination with glucosamine (see Glucosamine). The usual dose used by those with osteoarthritis is 1,200 milligrams daily in divided doses.
It usually takes several weeks of supplementation before effects, if any, are experienced.
Chondroitin sulfate in combination with hyaluronic acid is available as an FDA-approved drug. It is used as a viscoelastic agent in cataract surgery. Hyaluronic acid itself is FDA approved for the treatment of osteoarthritis. The two forms presently available, Hylan G-F 20 (Synvisc, Wyeth-Ayerst) and sodium hyaluronate (Hyalgan, Sanofi/Orthologic), are given by intra-articular injection.
HOW SUPPLIED
Capsules — 250 mg, 400 mg, 500 mg
Powder
Tablets — 250 mg, 400 mg, 600 mg
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