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)

The diagnosis of AOM in the infant and child requires an accurate history with special reference to fever, pain, and respiratory symptoms and a careful examination with particular attention to the appearance and movement of the TM. The practitioner must be wary of relying too heavily on any single physical finding, but instead consider all the variables that influence and alter the history and physical examination as summarized in Table 4. These variables include the reliability of the history, the history of previous infections, the age of the child, the appearance of the EAC, and the appearance and mobility of the TM. The importance of a correct diagnosis is crucial because of the immediate treatment and follow-up dictated by the diagnosis and because of the potential long-term effects on the child's health and development, which are described in the remaining articles in this issue of Pediatric Annals.
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PMID:Pitfalls in diagnosing acute otitis media. 156 Sep 97

E5090 is a novel orally active inhibitor of IL-1 generation without cyclooxygenase-inhibiting activity. The effects of E5090 on several inflammatory animal models were investigated in rats. In adjuvant arthritis, E5090 suppressed both the paw swelling and the enhancements of ESR and number of peripheral blood leucocytes, like the steroidal antiinflammatory drug prednisolone. However, the thymus was not withered by E5090 though it was by prednisolone. In type II collagen-induced arthritis, E5090 inhibited paw swelling and joint destruction. E5090 was effective in acute inflammatory models such as carrageenin-induced paw edema, and adjuvant-induced local hyperthermia, and also showed analgesic effects against inflammatory pain and antipyretic effects. The results suggest that this orally active inhibitor of IL-1 generation, E5090, may be a therapeutically useful antiinflammatory drug with a novel mechanism of action.
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PMID:Antiinflammatory properties of E5090, a novel orally active inhibitor of IL-1 generation. 206 90

The antiinflammatory activity of the novel pyrrolidin-2-one derivative N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-o ne (E-5110) was investigated and compared with those of indomethacin and piroxicam in various antiinflammatory, analgesic and antipyretic animal models. The acute antiinflammatory activity of E-5110 on the carrageenin paw edema was similar to that of indomethacin, and half that of piroxicam. The chronic inflammatory responses in established adjuvant- and type II collagen-induced arthritis, which are widely used models of rheumatoid arthritis, were suppressed as effectively by E-5110 as by indomethacin and piroxicam. E-5110 decreased the pleural exudate volume and inhibited leucocyte infiltration in a reversed passive Arthus reaction more potently than indomethacin, suggesting that mediators other than prostaglandin E2 may play an important role in this inflammatory process. The analgesic potency of E-5110 against inflammatory pain was similar to that of indomethacin or piroxicam, but the antipyretic activity of E-5110 was more potent than that of the reference drugs. The ulcerogenic effect of E-5110 on rat gastric mucosa was less than those of indomethacin and piroxicam. In conclusion, E-5110 is a very potent antiinflammatory compound acting against various types of inflammation, and has a favorable therapeutic index.
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PMID:Pharmacological properties of the novel non-steroidal antiinflammatory agent N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2 -one. 349 9

Relapsing polychondritis is an uncommon disease consisting of inflammation of the eyes, inner ears, cardiovascular system, and cartilaginous portions of the joints, respiratory tract, and external ear. Cutaneous manifestations are the presenting feature in more than 50% of patients. These usually consist of erythema, swelling, and pain, reflecting involvement of the underlying cartilage. Direct involvement of the skin may occur as vasculitis, lesions resembling erythema nodosum, or nonspecific eruptions. The presence of circulating antibodies to type II collagen--more against native than denatured collagen--and to human fetal cartilage, and the presence of circulating immune complexes suggest a primary role for antibody in the pathogenesis of relapsing polychondritis. There is no ideal treatment, but systemic corticosteroids and dapsone seem most effective.
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PMID:Relapsing polychondritis. 388 8

Adjuvant arthritis is an experimental immunopathy that is thought to share many features of human rheumatoid arthritis and, as such, is one of the most widely used models for studying the anti-inflammatory properties of compounds. Adjuvant arthritis can be induced in the rat by the injection of various bacterial cell walls or their components; however, the exact immunogen remains unknown. Recently, an autoantibody response to type II collagen was described not only in the collagen-induced arthritic model but in the adjuvant-induced disease as well. This response thus suggests that shared antigenic determinants exist between type II collagen and the responsible immunogen in the bacterial cell wall components. The contribution of the T lymphocyte to the pathogenesis of adjuvant arthritis is well known. It has now been shown that under specific conditions, adjuvant arthritis can be either enhanced or suppressed with pharmacologic or surgical manipulation, thus suggesting the heterogenicity of T lymphocytes capable of influencing the course of the disease. Levamisole was shown to reverse the augmentation of adjuvant disease seen after adult thymectomy, which suggests that levamisole can restore an aberrant immune response. Monoclonal antibodies are now being developed to evaluate T cell subsets in the rat. The use of these antibodies to study or selectively deplete lymphocyte subpopulations in this disease model promises to reveal immunologic characteristics that may lead to the development of new classes of immunoregulant drugs. Finally, the adjuvant rat has been found useful as a pain model capable of detecting the analgesic properties of both central and the newer peripheral analgesics. The above studies further corroborate the similarities between the immunopathological and hyperalgesic features of human rheumatoid arthritis and adjuvant disease. Recently developed immunologic technology may allow a new look at an old model and may result in the ability to evaluate new classes of immunoregulating agents.
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PMID:Adjuvant arthritis: immunopathological and hyperalgesic features. 617 58

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

Many types of injuries to the meniscus of the knee joint result in defects that do not heal, leading to pain and dysfunction. Several ongoing investigations are developing porous absorbable matrices to be used alone or seeded with cultured cells to facilitate regeneration of this tissue. The objective of this study was to evaluate in vitro the contractile behavior of meniscal cells seeded in type I and type II collagen matrices. In many connective tissues, fibroblasts that have assumed a contractile phenotype (myofibroblasts) have been found to play an important role in healing and in pathological conditions. This phenotype, if expressed by meniscal cells, could affect their behavior in cell-seeded matrices developed for tissue engineering. In this study, the presence of a contractile actin isoform, alpha-smooth muscle (alpha-SM) actin, was assessed by immunohistochemistry in normal calf meniscal tissue and in meniscal cells in 2- and 3-dimensional culture. Calf meniscus cells were seeded in type I and type II collagen-glycosaminoglycan (GAG) matrices. The diameter of the matrices was measured every 2-3 days. Immunohistochemical staining of the 2-dimensional cultures for alpha-SM actin was performed after 1, 3, and 7 days and the staining of the seeded matrices was at 1, 7, 14, and 21 days. Transmission electron microscopy (TEM) was performed on selected samples. After 3 weeks the seeded type I matrices displayed a significant shrinkage of almost 50% whereas the type II matrix and both types of unseeded controls showed almost no contraction over the same time period. Positive staining for the alpha-SM actin phenotype was seen in 10% of the cells of the normal tissue but was present in all cells seeded in monolayer and in both types of matrices. TEM of representative cell-seeded matrices showed microfilaments approximately 7 nm thick, consistent with the myofibroblast phenotype. This is the first report of alpha-SM actin containing cells in the knee meniscus. The finding that, under certain conditions, meniscal cells can express the myofibroblast phenotype warrants study of their role in meniscal healing and the tissue response to implants to facilitate tissue regeneration.
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PMID:alpha-smooth muscle actin and contractile behavior of bovine meniscus cells seeded in type I and type II collagen-GAG matrices. 1039 71

HLA-B27 is highly linked with a group of human diseases called spondyloarthropathies (SpA). Many of these disorders begin after an infection with an enterobacteria. The symptoms seen in patients with spondyloarthropathies are inflammatory pain in the spine and asymmetrical arthritis of lower limbs. Additional symptoms related to SpA include inflammation in the eyes, bowel, and skin. The autoantigen(s) in SpA are not known. Proteins such as collagen and proteoglycans have been thought to be potent autoantigens in arthritidis including B27-associated human diseases. Type II collagen is a common denominator among eyes and joints, affected tissues in B27-linked diseases. Moreover, a few reports indicated CII specific T cells and antibodies in patients with spondyloarthropathies. We and others have previously described development of spontaneous arthritis and nail disease in HLA-B27 transgenic animals. To determine whether CII may be a target antigen in the B27-linked diseases, B27 + m beta 2 m% (HLA-B27) transgenic mice lacking mouse beta 2m with and without human beta 2m) mice were immunized with type II collagen inside the barrier facility. Male HLA-B27 transgenic mice developed collagen-induced arthritis compared to transgene negative littermates or female counterparts. There was no difference in the incidence of arthritis in HLA-B27 transgenic mice with and without human beta 2m. Our data suggest that beta 2m free heavy chain of HLA-B27 may present soluble antigens such as type II collagen to trigger specific T cells contributing in the development of arthritis. Our data also suggest that CII may be a potential target antigen in the cartilage during the disease process.
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PMID:HLA-B27 transgenic mice are susceptible to collagen-induced arthritis: type II collagen as a potential target in human disease. 1071 6

Arthritis afflicts approximately 43 million Americans or approximately 16.6% of the US population. The two most common and best known types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). A significant amount of scientific research has been done in attempts to explain what initiates forms of arthritis, how it is promoted and perpetuated and how to effectively intervene in the disease process and promote cartilage remodeling. Current pharmacological strategies mainly address immune suppression and antiinflammatory mechanisms and have had limited success. Recent research provides evidence that alterations in the three-dimensional configuration of glycoproteins are responsible for the recognition/response signaling that catalyzes T-cell attack. Oral administration of autoantigens has been shown to suppress a variety of experimentally induced autoimmune pathologies, including antigen-induced RA. The interaction between gut-associated lymphoid tissue in the duodenum and epitopes of orally administered undenatured type II collagen facilitates oral tolerance to the antigen and stems systemic T-cell attack on joint cartilage. Previous studies have shown that small doses of orally administered undenatured type II chicken collagen effectively deactivate killer T-cell attack. A novel glycosylated undenatured type II collagen material (UC-II) was developed to preserve biological activity. The presence of active epitopes in the UC-II collagen is confirmed by an enzyme-linked immunosorbent assay test and distinguishes this form from hydrolyzed or denatured collagen. Oral intake of small amounts of glycosylated UC-II presents active epitopes, with the correct three-dimensional structures, to Peyer's patches, which influences the signaling required for the development of immune tolerance. UC-II has demonstrated the ability to induce tolerance, effectively reducing joint pain and swelling in RA subjects. A pilot study was conducted for 42 days to evaluate the efficacy of UC-II (10 mg/day) in five female subjects (58-78 years) suffering from significant joint pain. Significant pain reduction including morning stiffness, stiffness following periods of rest, pain that worsens with use of the affected joint and loss of joint range of motion and function was observed. Thus, UC-II may serve as a novel therapeutic tool in joint inflammatory conditions and symptoms of OA and RA.
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PMID:Effects of orally administered undenatured type II collagen against arthritic inflammatory diseases: a mechanistic exploration. 1283 47

CORRELATIONS OF BIOLOGICAL MARKERS: Ten biological markers collected from blood or urine were analysed in the ECHODIAH cohort (patients with hip OA with a 3 Years follow up). In multivariate analysis, after adjustment for age, gender, and body mass index, some markers were found to be significantly correlated with clinical and radiological parameters. C-telopeptide of type II collagen (CTX-II) was correlated with pain, functional impairment, joint space narrowing, and subchondral sclerosis. C-reactive protein was correlated with pain. N-propeptide of type I collagen (PINP) was correlated with functional impairment, and cartilage oligomeric matrix protein (COMP) was correlated with inflammation. PREDICTIVE VALUE OF BIOLOGICAL MARKERS: High levels of urinary C-telopeptide of type II collagen (uCTX-II), a marker of cartilage degradation, and serum hyaluronic acid (sAH), a marker of synovial inflammation, were associated with higher risk of structure degeneration in osteoarthritis patients. Combined assay of these two markers could help identify patients with a higher risk of radiological progression, but many questions remain to be resolved.
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PMID:[Biological markers of osteoarthritis: data from the ECHODIAH cohort]. 1522 84


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