Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of two arginine-specific cysteine proteinases (gingipain Rs) from Porphyromonas gingivalis, a causative bacterium of adult periodontitis, on human blood coagulation was investigated. Activated partial thromboplastin time and prothrombin time were shortened by these proteinases, with a 95-kDa gingipain R containing adhesin domains being 5-fold more efficient in comparison to a 50-kDa gingipain R containing the catalytic domain alone. The 50-kDa enzyme reduced each coagulation time in several plasmas deficient in various coagulation factors, while it was ineffective in factor X-deficient plasma unless reconstituted with this protein. Each proteinase activated factor X in a dose- and time-dependent manner, with Michaelis constants (Km) being found to be lower than the normal plasma factor X concentration, strongly suggesting that factor X activation by gingipain Rs, especially the 95-kDa form which is strongly activated by phospholipids, could occur in plasma. This is the first report of factor X activation by bacterial proteinases and indicates that the gingipain Rs could be responsible for the production of thrombin and, indirectly, with the generation of prostaglandins, interleukin-1, etc., which have been found to be associated with the development of periodontitis induced by P. gingivalis infections. Furthermore, the data support the hypothesis that induction of blood coagulation by bacterial proteinases may be a causative agent in the pathogenesis of disseminated intravascular coagulation in sepsis.
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PMID:Activation of blood coagulation factor X by arginine-specific cysteine proteinases (gingipain-Rs) from Porphyromonas gingivalis. 918 12

The effect of two arginine-specific cysteine proteinases (gingipains R) from Porphyromonas gingivalis, an aetiological factor of adult periodontitis, on the activation of human factor IX was investigated in the presence of ethylene glycol, an activity enhancer of activated factor IX (factor IXa), with the use of a fluorogenic oligopeptide substrate. Each gingipain R rapidly activated factor IX but the 95 kDa proteinase complex (HRgpA) that contains both haemagglutinin/adhesion and catalytic domains was 2.4-fold more efficient than the single-chain 50 kDa gingipain R (RgpB), which has only a catalytic domain. SDS/PAGE and N-terminal sequence analysis of factor IX digestion fragments indicated that, like all endogenous activators, gingipains R also produce factor IXabeta via an IXa intermediate. Significantly, phospholipids augmented the activation of factor IX by HRgpA but not by RgpB in a Ca(2+)-dependent manner. In the presence of both cofactors the kinetic efficiency of HRgpA to activate factor IX (k(cat)/K(m)=1.9x10(6) M(-1).s(-1)) was 8.5-fold higher than that of RgpB (k(cat)/K(m)=2.3x10(5) M(-1).s(-1)) and double that of the factor VIIa-tissue factor complex, but 8-fold lower than that for factor XIa. A comparison of the relative activation rates of factor IX, factor X and prothrombin directly in plasma by HRgpA suggests a significant contribution for factor IX conversion in blood coagulation induced by gingipains R. Taken together, gingipains R are the first-reported activators of factor IX of bacterial origin. By this effect they could be involved in the production of thrombin as well as the subsequent generation of prostaglandins and interleukin 1, all of which have been found to be associated with the development and progression of periodontitis.
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PMID:Activation of blood coagulation factor IX by gingipains R, arginine-specific cysteine proteinases from Porphyromonas gingivalis. 1113 97

Cigarette smoking, hypertension, hypercholesterolemia, and periodontal disease have been established as major risk factors for cardiovascular disease. Dentists and physicians should work aggressively to educate periodontitis patients about this relationship in an effort to improve the quality of health and contribute to their long-term survival. Blood pressure should be checked at the initial dental visit and at each subsequent visit in patients whose blood pressure is found to be high and/or has a history of hypertension. Dental and medical assistants should receive in-service training to assure competency in measuring blood pressures. All staff should be certified in basic cardiopulmonary resuscitation. Emergency protocol procedures should be in writing and rehearsed regularly. Patients should take their blood pressure medication as usual on the day of the dental procedure. It is helpful for the patients to bring all medications to the office for review at the time of the dental procedure. Good communication should be established between the dentist and physician to maximize good dental and physical health. Because the patient with periodontal disease is at an increased risk for cardiovascular disease, a standardized form should be developed for the convenient exchange of vital information, including but not limited to: blood pressure, medications, allergies, medical conditions and pertinent highlights of dental procedures. Minimize stress in patients with coronary artery disease. This includes providing solid local anesthesia, avoidance of intravascular medication injections, and encouraging relaxation techniques. Antibiotic prophylaxis is indicated in patients with valvular heart disease but does not guarantee the prevention of endocarditis. These patients should be alerted to monitor any symptoms such as fever, chills or shortness of breath. It has also been documented that toothbrushing, flossing and home plaque removers can cause transient bacteremia in periodontal patients. Epinephrine use should be avoided or utilized cautiously in patients with pacemakers or automatic defibrillator devices because of the possibility of refractory arrhythmia. Consultation with patient's cardiologist is advised. Anticoagulation with coumadin is not a contraindication to dental procedures. The prothrombin time or international normalized ratio laboratory values should be checked on the day of the procedure to assure that it is in an acceptable range. Aspirin therapy is not a problem unless the patient is on very high doses for severe arthritis. Continuing medical and dental education credits should emphasize cross-training in both areas to insure comprehensive treatment of the patient with periodontal disease. Smoking cessation, regular exercise, a low-fat diet and good dental hygiene contribute to a healthy cardiovascular system. Patients should understand as best we know the relationship between periodontal and cardiovascular disease to afford them an opportunity to improve their overall dental and physical health.
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PMID:Medical management of the patient with cardiovascular disease. 1127 61

The effect of 95- (HRgpA) and 50-kDa gingipain R (RgpB), arginine-specific cysteine proteinases from periodontopathogenic bacterium Porphyromonas gingivalis on human prothrombin activation was investigated. Each enzyme released thrombin from prothrombin in a dose- and time-dependent manner with the former enzyme, containing adhesion domains, being 17-fold more efficient than the single chain RgpB. A close correlation between the generation of fibrinogen clotting activity and amidolytic activity indicated that alpha-thrombin was produced by gingipains R, and this was confirmed by SDS-polyacrylamide gel electrophoresis, thrombin active site labeling, and amino-terminal sequence analysis of prothrombin digestion fragments. Significantly, the catalytic efficiency of HRgpA to generate thrombin (k(cat)/K(m) = 1.2 x 10(6) m(-)1 s(-)1) was 100-fold higher than that of RgpB (k(cat)/K(m) = 1.2 x 10(4) m(-)1 s(-)1). The superior prothrombinase activity of HRgpA over RgpB correlates with the fact that only the former enzyme was able to clot plasma, and kinetic data indicate that prothrombin activation can occur in vivo. At P. gingivalis-infected periodontitis sites HRgpA may be involved in the direct production of thrombin and, therefore, in the generation of prostaglandins and interleukin-1, both have been found to be associated with the development and progression of the disease. Furthermore, by taking into account that the P. gingivalis bacterium has been immunolocalized in carotid atherosclerotic plaques at thrombus formation sites (Chiu, B. (1999) Am. Heart J. 138, S534-S536), our results indicate that bacterial proteinases may potentially participate in the pathogenesis of cardiovascular disease associated with periodontitis.
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PMID:Activation of human prothrombin by arginine-specific cysteine proteinases (Gingipains R) from porphyromonas gingivalis. 1127 15

Chronic-degenerative dentistry diseases, including periodontal diseases and oral osteonecrosis, are widespread in human populations and represent a significant problem for public health. These diseases result from pathogenic mechanisms created by the interaction between environmental genotoxic risk-factors and genetic assets conferring individual susceptibility. Osteonecrosis occurs in subjects undergoing exposure to high doses of DNA-damaging agents for chemo- and radiotherapy of neoplastic diseases. In susceptible patients, ionizing radiation and biphosphonate-chemotherapy induce severe, progressive, and irreversible degeneration of facial bones, resulting in avascular necrosis of the jaw. This may also occur in patients receiving biphosphonate for osteoporosis therapy. Periodontal diseases include chronic, aggressive, and necrotizing periodontitis, often resulting in severe alteration of periodontal tissues and tooth loss. Cigarette smoking and chronic inflammation caused by specific bacteria are the main risk factors for periodontitis. Oxidative damage plays a fundamental pathogenic role, as established by detection of mitochondrial DNA damage in the gingival tissue of patients with periodontitis. Endogenous risk factors in dental diseases include polymorphisms for metabolic enzymes such as glutathione transferases M1 and T1, N-acetyl transferase 2, and CYP 1A1. Other genetic polymorphisms that confer susceptibility to dentistry diseases affect genes encoding metalloproteases (involved in periodontal tissue remodeling and degradation), cytokines (involved in inflammation), prothrombin, and DNA repair activities. These findings provide evidence that dentistry diseases are related to risk factors associated with environmental mutagenesis. This issue warrants future investigations aimed at improving oral health and preventing oral degenerative diseases using molecular and experimental approaches currently utilized in mutagenicity studies.
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PMID:Degenerative periodontal-diseases and oral osteonecrosis: the role of gene-environment interactions. 1905 6