Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the effects of piroxicam on cartilage metabolism in vivo, a three phase (placebo/piroxicam 20 mg/day by mouth/placebo) double blind controlled trial was conducted in patients with osteoarthritis of the knee joint. Twenty one patients were recruited, 19 of whom (11 women, eight men, median age 70 years) completed the treatment schedule. The knee joint under study was aspirated to dryness at four week intervals. Treatment with piroxicam was accompanied by a decrease in the pain score, an improvement in the functional index, and an increased range of movement. Reductions in the concentration (mean (SEM) 120 (6) to 110 (8) micrograms/ml) and the total amount (1.22 (0.34) to 0.99 (0.37) mg) of keratan sulphate, but not the effusion volume (9.4 (2.5) to 8.3 (2.6) ml) were observed during treatment with piroxicam. These findings are consistent with decreased proteoglycan catabolism during treatment with piroxicam. Neither depressed synthesis nor enhanced clearance of degraded proteoglycan fragments can be excluded, however.
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PMID:Reduction of the concentration and total amount of keratan sulphate in synovial fluid from patients with osteoarthritis during treatment with piroxicam. 163 58

Health practitioners use many methods and agents to bring on cervical ripening in early pregnancy, such as intracervical tents and pharmacological techniques, to induce a therapeutic abortion. Prostaglandins alter myometrial and cervical tissue and are the most often used pharmacological technique. Reduced collagen concentration, an increase in water volume, an increase in prostaglandins (PGE2, PGI2, and PGF2 alpha), and a change in the glycosaminoglycan (GAG) content coincide with cervical ripening, yet the mechanism responsible for these changes is obscure. Prostaglandins appear to cause the breakdown of collagen or change the GAG/proteoglycan content. Research shows that prostaglandins can initiate cervical ripening at any stage of pregnancy. Estradiol stimulates prostaglandin production thereby al so inducing cervical dilation. Relaxin also demonstrates an ability to ripen the cervix. In addition, mifepristone (RU-486) is gaining acceptance as a cervical ripening agent. In fact, RU-486 and gemeprost have at least 95% success rate compared to 92% for gemeprost alone or 85% with RU-486 alone. The only effective and acceptable prostaglandins to use at gestation of 0-8 weeks are sulprostone, gemeprost, and 9-methylene-PGE2. At t his gestational age, pharmacological modulation is all that is needed. Even though they are effective (abortion rate 90%), side effects are expected to occur (pain, nausea, and vomiting). Similarly, prostaglandin analogues are preferable for cervical ripening in women at 8-12 weeks gestation. Suction curettage or other surgical techniques then are used to remove the conceptus. At 12-16 weeks gestation, many physicians prefer the same protocol as that of 8-12 weeks gestation. Other choose to infuse PGE2 and saline into the amniotic fluid to stimulate uterine contractions. Another procedure at 12-16 weeks involves 1mg vaginal pessaries of gemeprost every 3 hours to ripen the cervix and stimulate contractions. After 16 weeks, the methods for 12-16 weeks still apply.
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PMID:Pharmacological modulation of cervical compliance in the first and second trimesters of pregnancy. 187 72

Six normal horses received 3 intra-articular injections of sodium monoiodoacetate (MIA) in the distal intertarsal (DIT) and tarsometatarsal (TMT) joints of one hindlimb. Injections were at three week intervals, and post injection pain was controlled with routine administration of phenylbutazone for five days following each injection. All horses underwent a gradually increasing exercise programme consisting of walking and trotting beginning one week after the first injection and continuing for 24 weeks. All treated joints showed increasingly severe radiographic evidence of degenerative joint disease with time. Clinical signs were mild or absent during exercise. All treated joints showed radiographic and histological evidence of fusion 24 weeks after the first injection. Amount of radiographic fusion ranged from 54.49 per cent to 88.64 per cent of the joint space. Histologically, the joint space that appeared radiographically fused was filled mainly with woven and lamellar bone. Fibrocartilage and fibrous tissue was seen frequently in the transition between fused and unfused areas. Articular cartilage in unfused areas was thin, fibrillated, hypocellular and histochemically showed diminished proteoglycan content. Existing joint space was filled with fibrin and necrotic, acellular chondroid matrix. We conclude that MIA will produce fusion of the DIT and TMT joints of normal horses in 24 weeks, and may offer a relatively easy, inexpensive and non-invasive treatment for distal tarsal osteoarthritis in the horse.
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PMID:Fusion of the distal intertarsal and tarsometatarsal joints in the horse using intraarticular sodium monoiodoacetate. 191 30

It is clear that some synovial inflammation occurs in joints affected by osteoarthritis (OA) and it is well recognized that many patients with OA experience a decrease in pain and joint stiffness following administration of salicylates or other nonsteroidal antiinflammatory drugs (NSAIDs). However, neither the extent to which synovitis contributes to the cartilage breakdown in OA nor the effects of chronic administration of NSAIDs on the natural history of OA in humans is known. Recent studies indicate that several NSAIDs, including salicylates, suppress proteoglycan synthesis in articular cartilage in vitro. The effect on OA cartilage is more marked than that on normal cartilage. Other studies show that salicylate feeding may suppress proteoglycan metabolism in degenerating cartilage in vivo, aggravating the decrease in proteoglycan content caused by the disease itself. However, no effect of salicylates on normal articular cartilage has been observed in vivo. In damaged cartilage the magnitude of NSAID-induced suppression of proteoglycan metabolism appears to be related inversely to the proteoglycan content of the tissue. In addition, the NSAIDs used in treatment of arthritis today may differ with respect to their in vivo effects on articular cartilage metabolism due, in part, to differences between the molar concentrations of these drugs in synovial fluid.
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PMID:Nonsteroidal antiinflammatory drugs in treatment of osteoarthritis. 378 Jan 6

Biopsy specimens of cartilage and subchondral bone were obtained from the weight-bearing dome of the acetabulum in twelve elderly patients who were having a revision of a hemiarthroplasty of the hip because of pain. Biopsy specimens of acetabular cartilage and subchondral bone were also obtained from eight patients of comparable age who were having a primary hemiarthroplasty for a displaced fracture of the femoral neck; these served as the control specimens. The specimens were stained with hematoxylin and eosin for the initial histological assessment of cartilage structure and cellularity as well as the integrity of the tidemark. Safranin-O and toluidine-blue stains were used to assess proteoglycan content. A histological grading scale was employed for comparative analysis of samples. The joint space of the hip was measured on the radiographs that were made before the revision and was correlated with the histological grade. Review of the histological specimens demonstrated considerable degeneration of acetabular cartilage in the patients who were having a revision of a hemiarthroplasty as compared with that in the age-matched control patients who were having a primary hemiarthroplasty. The progression in the severity of the degeneration correlated directly with the duration of articulation of the implant with the acetabulum. All six of the patients in whom the implant had been in situ for more than five years, and in whom the femoral stem was determined to be stable at the operation, had nearly complete loss of cartilage as seen on histological examination.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rate of degeneration of human acetabular cartilage after hemiarthroplasty. 860 47

The distribution and arrangement of extracellular matrix proteins were examined in the primate temporomandibular joint disc and posterior attachment using a combination of light microscopic, immunohistochemical, and biochemical techniques. The band areas of the disc contain a complex collagenous (type I) fiber network consisting of a mediolaterally directed fiber bundle system that interlaces or becomes continuous with an anteroposteriorly directed collagenous fiber array that runs through the intermediate zone. Thin, branching, elastic fibers are a significant component of the disc and are generally oriented parallel to the collagenous fiber network. Interfibrillar spaces in band areas contain numerous chondrocytes encased within a matrix that is rich in a high molecular weight, predominantly chondroitin-sulfate proteoglycan and type II collagen. The intermediate zone appears tendinous in its construction and is composed of anteroposteriorly oriented elastic and collagenous fibers, scattered chondrocytes, and reduced amounts of chondroitin-sulfate proteoglycan and type II collagen. The posterior attachment is composed of fibrocytes, larger caliber elastic fibers, loosely organized type I collagenous fibers, and low molecular weight dermatan-sulfate proteoglycan. These results indicate that the primate temporomandibular joint disc is a microheterogenous tissue with distinct regional specializations.
J Orofac Pain 1994
PMID:Morphologic, microscopic, and immunohistochemical investigations into the function of the primate TMJ disc. 792 Mar 50

A single intra-articular (ia) injection of 2 mg zymosan on D0 led to the production of acute periarticular edema followed by subacute erosive synovitis. The development of the zymosan-induced arthritis was associated with an initial loss of running activity and with an initial decrease of proteoglycan synthesis. Febrile response was present only on D1. In addition, on D20 synovial pannus led to a marked depletion of the proteoglycan content in the articular cartilage. When injected ia, IL1 beta (1 microgram) provoked similar fever and similar changes in cartilage anabolism, but did not affect cartilage proteoglycan content (D20). These results suggest that zymosan-induced synovitis in the rat combines early prostaglandin-dependent processes (edema, pain, fever) with IL1-related effects on cartilage metabolism, thus allowing evaluation of chondroprotective drugs.
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PMID:Characterization of zymosan-induced arthritis in the rat: effects on joint inflammation and cartilage metabolism. 793 34

Osteoarthritis results from progressive catabolic loss of cartilage proteoglycans, owing to an imbalance between synthesis and degradation. Standard drug therapy is only of palliative benefit and may exacerbate loss of cartilage. Glucosamine is an intermediate in mucopolysaccharide synthesis, and its availability in cartilage tissue culture can be rate-limiting for proteoglycan production. A number of double-blind studies dating from the early 1980s demonstrate that oral glucosamine decreases pain and improves mobility in osteoarthritis, without side effects. Nevertheless, medical researchers and physicians in the US have totally ignored this rational and safe therapeutic strategy. By mechanisms that are still unclear, the natural methyl donor S-adenosylmethionine also promotes production of cartilage proteoglycans, and is therapeutically beneficial in osteoarthritis in well-tolerated oral doses. These and other safe nutritional measures supporting proteoglycan synthesis, may offer a practical means of preventing or postponing the onset of osteoarthritis in older people or athletes.
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PMID:The neglect of glucosamine as a treatment for osteoarthritis--a personal perspective. 793 75

The main "shock absorbing" molecule in cartilage is the proteoglycan, aggrecan, which is trapped within a meshwork of collagen fibrils. Articular cartilage damage in osteoarthritis is associated with damage to the aggrecan protein moiety. This results in abnormal loss of aggrecan which in turn increases the propensity of the joint surface to be damaged. Presently, the treatment for arthritis, pain-relieving drugs, affects the symptoms. End-stage osteoarthritis requires joint replacement surgery. To a certain extent, both the degradation and the repair of cartilage can be understood at the level of the biochemistry of cartilage matrix and the biology of the chondrocyte.
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PMID:Cartilage aggrecan. Biosynthesis, degradation and osteoarthritis. 819 77

Intra-articularly administered, long-acting corticosteroids are a beneficial treatment for many equine joint disorders because they alleviate inflammation and signs of pain, but they also exert detrimental effects on the biochemical composition and morphologic features of articular cartilage. Chondroprotective drugs have been shown to mitigate some of the deleterious effects of intra-articularly administered corticosteroids on articular cartilage of laboratory animals. Twenty-one ponies were assigned at random to receive 1 of 3 treatments in the right middle carpal joint. Group-1 ponies (n = 8) had methylprednisolone acetate (MPA; 0.2 mg/kg of body weight) and saline solution administered intra-articularly and IM, respectively. Group-2 ponies (n = 9) received MPA (0.2 mg/kg) and polysulfated glycosaminoglycan (GAG; 2 mg/kg). Group-3 ponies (control; n = 4) had saline solution administered intra-articularly and IM. The corticosteroid or saline solution was injected into the right middle carpal joint on day 1. The IM administered polysulfated GAG or saline solution was administered at the same time, then was repeated every 3 days for 20 days. Ponies were euthanatized 21 days after initial injection by overdose of pentobarbital sodium. The cartilage of younger ponies was significantly (P < 0.05) more responsive to the proteoglycan-depleting effects of MPA. Ponies < 10 years old of groups 1 and 2 had significantly (P < 0.05) lower GAG content in the articular cartilage than did control ponies. Systemic treatment with polysulfated GAG did not result in a protective effect against proteoglycan loss from the articular cartilage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of intramuscularly administered polysulfated glycosaminoglycan on articular cartilage from equine joints injected with methylprednisolone acetate. 821 10


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