Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stroke is accompanied by a strong inflammatory reaction in the brain. Periodontal disease is a chronic local infection which causes a systemic low grade inflammation. We hypothesized that a mild systemic inflammatory reaction as caused by periodontal disease prior to stroke onset, may exert a neuroprotective effect in a rat model of focal ischemia. To test this hypothesis, marginal periodontitis was induced by ligatures on the second maxillary molars in BB/LL Wistar rats for 3 weeks. Two weeks after periodontitis initiation, focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery. After a survival time of 7 days after ischemia, rats were killed and bone loss was determined on the buccal and palatinal surfaces of the defleshed jaw. In addition, markers of systemic inflammation were determined in a different group of laboratory animals at 14 days after the onset of periodontitis. The infarct size and markers of the inflammatory reaction in the brain were determined by immunohistochemistry. We found: (i) rats with ligatures exhibited significantly more periodontal bone loss than the control rats; (ii) the development of periodontitis was associated with an elevated gene expression for several markers of systemic inflammation (interleukin-10, transforming growth factor beta 1, tumor necrosis factor alpha, interleukin-1beta and interferon gamma; (iii) rats with periodontitis and a mild systemic inflammation had a significantly reduced infarct volume and a significant reduction in the number of brain macrophages in the infarcted area. In conclusion we found that mild systemic inflammation elicited prior to stroke onset may have a neuroprotective effect in rats by reducing the infarct volume and tissue destruction by brain macrophages.
 ...
PMID:Mild systemic inflammation has a neuroprotective effect after stroke in rats. 1899 56

Relationship between diabetes mellitus (DM) and periodontal disease has been the subject of many studies that underline that diabetic patients are two/three times more susceptible to have an increased risk of periodontal disease, especially when metabolic control is inadequate. In this review the authors analyze, in diabetic patient, biochemical, histological and microbiological aspects of periodontal disease. Recent studies reported the results obtained in not diabetic patients, both periodontopatic and not: in periodontopatic subjects, the value of glycated hemoglobin was higher. As regards type 2 DM has a positive relationship between periodontal inflammation and glycemia, with good probabilities of disease development. Some Authors showed how the hygiene and the professional/domiciliary control could support a reduction of the glycate hemoglobin and, therefore, of the periodontal disease. The glucose accumulation in the crevicular fluid, noticed in pockets with a depth >4 mm, causes an increase of spirochetes and bacteria. Some research reported that scarcely controlled patients show high levels of interleukin-1beta (IL-1beta). This alteration together with the prolonged expression of tumor necrosis factor (TNF) could represent a mechanism used by bacteria to cause a major damage during the inflammation process, sometimes favoured by immunological defects, due to the mobilization of lymphocytes subpopulations. By measuring the values of TNF-a, fibrinogen, high sensitive capsule reactive protein (hs-CRP), IL-4, IL-6, IL-8, IL-10, at the beginning of non-surgical periodontal therapy and it has been after 3 months of treatment, noticed a relevant reduction only of TNF-a and fibrinogen. Concerning vascular alteration, vascular endothelium growing factor (VEGF) could play a major role in the tissues ischemia. The VEGF should determine the tissue ischemia, the angiogenesis and the alteration of glucose haematic level, in patients affected by microvasculopathies due to diabetes and to periodontal diseases. Particularly, the angiogenesis should favor the chronic inflammation, caused by increasing concentration of cytokines and other pro-inflammatory factors.
 ...
PMID:Diabetes mellitus: biochemical, histological and microbiological aspects in periodontal disease. 2178 May 42

Various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis, spondyloarthritis, vasculitis and systemic lupus erythematosus, are associated with premature atherosclerosis. However, premature atherosclerosis has not been uniformly observed in systemic sclerosis. Furthermore, although experimental models of atherosclerosis support the role of antiphospholipid antibodies in atherosclerosis, there is no clear evidence of premature atherosclerosis in antiphospholipid syndrome (APA). Ischemic events in APA are more likely to be caused by pro-thrombotic state than by enhanced atherosclerosis. Cardiovascular disease (CVD) in ARDs is caused by traditional and non-traditional risk factors. Besides other factors, inflammation and immunologic abnormalities, the quantity and quality of lipoproteins, hypertension, insulin resistance/hyperglycemia, obesity and underweight, presence of platelets bearing complement protein C4d, reduced number and function of endothelial progenitor cells, apoptosis of endothelial cells, epigenetic mechanisms, renal disease, periodontal disease, depression, hyperuricemia, hypothyroidism, sleep apnea and vitamin D deficiency may contribute to the premature CVD. Although most research has focused on systemic inflammation, vascular inflammation may play a crucial role in the premature CVD in ARDs. It may be involved in the development and destabilization of both atherosclerotic lesions and of aortic aneurysms (a known complication of ARDs). Inflammation in subintimal vascular and perivascular layers appears to frequently occur in CVD, with a higher frequency in ARD than in non-ARD patients. It is possible that this inflammation is caused by infections and/or autoimmunity, which might have consequences for treatment. Importantly, drugs targeting immunologic factors participating in the subintimal inflammation (e.g., T- and B-cells) might have a protective effect on CVD. Interestingly, vasa vasorum and cardiovascular adipose tissue may play an important role in atherogenesis. Inflammation and complement depositions in the vessel wall are likely to contribute to vascular stiffness. Based on biopsy findings, also inflammation in the myocardium and small vessels may contribute to premature CVD in ARDs (cardiac ischemia and heart failure). There is an enormous need for an improved CVD prevention in ARDs. Studies examining the effect of DMARDs/biologics on vascular inflammation and CV risk are warranted.
...
PMID:Cardiovascular disease in autoimmune rheumatic diseases. 2354 82

Cardiovascular diseases are the leading cause of deaths. Also, cardiovascular risk factors start the atherosclerotic process, which leads to cardiovascular diseases. Nowadays, periodontal disease can also be considered another cardiovascular risk factor. It involves inflammatory, immunological and humoral activities, which induce the production of proinflammatory cytokines and the destruction of the epithelium. This allows the entry of endotoxins and exotoxins in the bloodstream, which may contribute to atherogenesis and thromboembolic events. There is also direct invasion of the vessel wall by oral pathogens, triggering an inflammatory response that produces endothelial dysfunction. In hypertension, changes in microcirculation can cause ischemia in the periodontium, which favors periodontal disease. Moreover, endothelial dysfunction promotes the formation of atherosclerotic plaque and the development of lesions in target organs. Periodontitis has also been associated with insulin resistance and a higher risk for the metabolic syndrome, which is characterized by oxidative stress. This seems to act as a common link to explain the relationship between each component of the metabolic syndrome (including hypertension) and periodontitis. This article will discuss clinical and experimental evidence, as well as possible pathophysiologic mechanisms and links involved in the relationship among periodontal disease, hypertension and cardiovascular disease.
...
PMID:Is there an association between periodontitis and hypertension? 2473 1

The High mobility group box 1 (HMGB1) protein is an extremely versatile, highly conserved nuclear protein, with its unique intracellular and extracellular functions mediated by its relatively simple domain structure. Within the nucleus, HMGB1 binds to DNA minor groove in a nonspecific manner and causes bends in the double helix thus helps in recruiting a number of DNA binding protein and transcription factors, to facilitate transcription of various genes. HMGB1 also helps in DNA repair, chromatin remodeling, V (D) J recombination, and assembly of nucleosome on the chromatin. On contrary, under pathological conditions HMGB1 displays inflammatory response by interaction with specific cell surface receptors like RAGE, TLR-4, TLR9, and TLR2 and activates NF-kB downstream signaling pathways. The upregulation of HMGB1 is directly associated with the pathogenesis of cancer, sepsis, ischemia, hemorrhagic shock, anorexia, rheumatic disease, periodontal disease etc. Therefore, HMGB1 has been considered as a promising target in the treatment of various human diseases. The interest in HMGB1 is evident and reflected in the exponential increase in the recent publications, and therefore there is a need for an update on the understanding of the role of HMGB1 in pathogenesis and its potential application of HMGB1 as a therapeutic target in a number of human diseases.
 ...
PMID:Dichotomous Life of DNA Binding High Mobility Group Box1 Protein in Human Health and Disease. 2691 60

Bone regeneration has been the ultimate goal in the field of bone and joint medicine and has been evaluated through various basic research studies to date. Translational research of regenerative medicine has focused on three primary approaches, which are expected to increase in popularity: cell therapy, proteins, and artificial materials. Among these, the local injection of a gelatin hydrogel impregnated with the protein fibroblast growth factor (FGF)-2 is a biomaterial technique that has been developed in Japan. We have previously reported the efficacy of gelatin hydrogel containing injectable FGF-2 for the regenerative treatment of osteonecrosis of the femoral head. Injectable growth factors will probably be developed in the future and gain popularity as a medical approach in various fields as well as orthopedics. Several clinical trials have already been conducted and have focused on this technique, reporting its efficacy and safety. To date, reports of the clinical application of FGF-2 in revascularization for critical limb ischemia, treatment of periodontal disease, early bone union for lower limb fracture and knee osteotomy, and bone regeneration for osteonecrosis of the femoral head have been based on basic research conducted in Japan. In the present report, we present an extensive review of clinical applications using injectable growth factors and discuss the associated efficacy and safety of their administration.
 ...
PMID:Clinical application of injectable growth factor for bone regeneration: a systematic review. 3166 90