Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0575090 (disturbed balance)
 228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue inhibitors of metalloproteinase (TIMP) and matrix metalloproteinases (MMP) are key elements in the formation, remodeling and degradation of matrix protein. Bone marrow fibrosis in AMM, with deposition, not only of interstitial and basement membrane collagen but also of fibronectin, vitronectin, laminin and proteoglycans, results from a disturbed balance between synthesis and proteolytic degradation of matrix protein. Although TIMP and MMP play important roles in the development of fibrosing diseases of skin, liver and lung, only a few studies of TIMP and MMP in the formation of bone marrow fibrosis in AMM have been published. The literature shows that TIMP-1 (both the total, complex and the free form) is significantly increased in AMM and other myeloproliferative syndromes (including polycythemia vera (PV) and essential thrombocytosis (ET)), while MMP-3 is significantly decreased, and levels of MMP-2 and MMP-9 are not different from control values. Variance from control values for both TIMP-1 and MMP-3 is more evident in AMM than in PV and ET, thus further suggesting bone marrow fibrosis in AMM results from enhanced TIMP and decreased MMP activities.
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PMID:Importance of plasma matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinase (TIMP) in development of fibrosis in agnogenic myeloid metaplasia. 1610 2

Tardive dyskinesia (TD) is a movement disorder described in individuals who have been treated with anti-dopaminergic agents. The pathophysiology of this condition remains to be fully elucidated. Several mechanisms like dopaminergic supersensitivity, dysfunction of striatonigral, GABAergic neurons and disturbed balance between dopaminergic and cholinergic systems have been described. Essential fatty acids (EFAs) are important components of neuronal membrane and the EFA content of these membranes can significantly influence neuronal functioning. Lower levels of EFAs have been reported in red blood cells (RBC) and plasma of individuals with moderate to severe TD. Supplementation with EFAs (omega-3 and omega-6 and ethyl-EPA) have been tried to alleviate TD in open and double-blind clinical trials and in some animal models of TD. In addition, antioxidants (Vitamin E) and melatonin have been tried. However, smaller numbers of patients and shortened length of clinical studies make it difficult to draw any definitive conclusions. Large multi-centre studies with sound methodology of both EFAs and antioxidants are needed.
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PMID:Tardive dyskinesia and essential fatty acids. 1677 67

Matrix metalloproteinases (MMPs) act in diverse physiological and pathological conditions such as tumor growth and angiogenesis by cleaving extracellular matrix and nonmatrix substrates. MMPs with gelatinase/collagenase activity have not yet been studied in juvenile angiofibroma, a unique fibrovascular tumor with prominent collagen expression. Quantitative real-time polymerase chain reaction studies, Western blot analysis, immunofluorescence studies, gel zymography, and in situ zymography were used to analyze MMP-1, MMP-2, MMP-9, MMP-13, MMP-14, TIMP-1, and TIMP-2 in 9 juvenile angiofibromas and 2 inferior nasal turbinate specimens. Quantitative real-time polymerase chain reaction found significantly elevated expression of MMP-2, MMP-9, and MMP-14 (P < .05) in tumor tissue compared with the inferior nasal turbinate specimens. Western blot analysis detected more prominent MMP-1, MMP-2, and MMP-9 protein levels in juvenile angiofibromas compared with inferior nasal turbinates, but not MMP-13, MMP-14, TIMP-1, and TIMP-2. Immunofluorescent staining proved a mainly stromal localization of the analyzed MMPs. Only MMP-9 and MMP-14 were also detected in vessel walls. MMP-1, MMP-2, and MMP-13 also stained mast cells. Gel zymography indicated increased MMP-2 and MMP-9 gelatinase activity in juvenile angiofibromas compared with inferior nasal turbinates. Finally, in situ zymography detected very high stromal gelatinase/collagenase activity. This study indicates significant expression of MMPs with gelatinase/collagenase activity in juvenile angiofibromas with evidence of a disturbed balance of MMPs to TIMPs toward enhanced MMP activity. These MMPs are assumed to be involved in tumor pathology with an influence on tumor growth and angiogenesis.
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PMID:Metalloproteinases in juvenile angiofibroma--a collagen rich tumor. 1795 Jul 79

Treatment with lipid-lowering drugs, statins, is common all over the world. Lately, the occurrence of spontaneous tendon ruptures or tendinosis have suggested a negative influence of statins upon tendon tissue. But how statins might influence tendons is not clear. In the present study, we investigated the effect of statin treatment on mechanical strength, cell proliferation, collagen content and gene expression pattern in a tendon-like tissue made from human tenocytes in vitro. Human tendon fibroblasts were grown in a 3D tissue culture model (tendon constructs), and treated with either simvastatin or atorvastatin, low or high dose, respectively, for up to seven days. After seven days of treatment, mechanical testing of the constructs was performed. Collagen content and cell proliferation were also determined. mRNA levels of several target genes were measured after one or seven days. The maximum force and stiffness were reduced by both statins after 7 days (p<0.05), while the cross sectional area was unaffected. Further, the collagen content was reduced by atorvastatin (p = 0.01) and the cell proliferation rate was decreased by both types of statins (p<0.05). Statin treatment also introduced increased mRNA levels of MMP-1, MMP-3, MMP-13, TIMP-1 and decreased levels of collagen type 1 and 3. In conclusion, statin treatment appears to have a negative effect on tendon matrix quality as seen by a reduced strength of the tendon constructs. Further, activated catabolic changes in the gene expression pattern and a reduced collagen content indicated a disturbed balance in matrix production of tendon due to statin administration.
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PMID:Simvastatin and atorvastatin reduce the mechanical properties of tendon constructs in vitro and introduce catabolic changes in the gene expression pattern. 2826 97