シカ チリョウ ト カンセンセイ シンナイマクエン ノ ヨボウ

Infective endocarditis is a serious infection of the endothelial surfaces of the heart, especially at the valves. Oral commensal bacteria are the most common etiologic agents of this disease. Infective endocarditis can be established when all the 3 conditions are present simultaneously, i.e., (1) the introduction of bacteria into the bloodstream, (2) predisposing impairments in the heart, and (3) the virulence of bacteria. Common dental procedures, even non-surgical dental procedures, can often cause bacteremia of oral commensals. Periodontally diseased patients are at risk from bacteremia even after brushing the teeth or eating meals. Bacteremia itself rarely affect healthy people but they can result in mortal infective endocarditis in those who have a predisposed risk for this disease, such as those with heart valve diseases, pacemaker implantation, etc. Despite advances in diagnosis, antimicrobial therapies, surgical techniques and management of complications, patients with infective endocarditis still have substantial mortality. To prevent this infection, antibiotics is currently used, however, their frequent uses generates drug-resistant mutant bacteria, which is a serious social problem. Therefore, development of novel alternative drugs to be used instead of the current antibiotics is highly desired. We are now using several types of combinatorial peptide libraries to search for small size molecular mimetics that can interfere with the adhesion of bacteria to the target tissue. The use of such peptides is expected to lead to the development of compounds for a novel preventive drug which does not kill bacteria, thus making it safer and less likely to generate drugresistant mutants

シシュウビョウ ヨボウ ト セイカツ シュウカン ソシテ セイカツ シュウカンビョウ ヨボウ ト シシュウビョウ

The onset and progression of periodontal disease is closely associated with patients’ lifestyles and habits, such as smoking, diet, stresses, etc. ; it is therefore considered to be a lifestyle-related disease. It is now listed as one of the complications of diabetes mellitus, as well as disorders of the retina, kidney, nervous system, heart, and brain. In addition to the concept that lifestyles and lifestyle-related diseases are causative factors of periodontal disease, this disease has now been revealed to be involved in the onset and progression of other systemic diseases, such as diabetes, as well as atherosclerosis, which leads to ischemic heart and brain diseases. Proinflammatory cytokines produced in the inflamed gingivae locally and bacteremia induced through the periodontal ulcerative lesions have been suggested to connect the local and systemic disorders. Periodontal diseases can be controlled by adequate risk management and oral health promotion, and this, in turn, contributes to risk reduction for other life-threatening systemic diseases

Infective endocarditis and dental procedures : evidence, pathogenesis, and prevention

Infective endocarditis is a serious infection occurring on the endothelial surfaces of the heart, especially at the valves. Oral commensal bacteria are the important etiologic agents in this disease. Common dental procedures, even non-surgical dental procedures, can often cause bacteremia of oral commensals. Periodontally diseased patients are at risk from bacteremia even after brushing the teeth. Bacteremia itself rarely affect healthy people but they can result in mortal infective endocarditis in those who have a predisposed risk for this disease, such as those with heart valve diseases, pacemaker implantation, etc. Infective endocarditis is thus established when all the 3 conditions are present simultaneously, i.e., 1) a predisposing impairments in the heart, 2) the introduction of bacteria into the bloodstream, and 3) the virulence of bacteria. Antibiotics have to be adequately used to prevent this infection, however, their frequent uses generates drug-resistant mutant bacteria, which is a serious social problem. The development of novel alternative drugs to be used instead of the current antibiotics is thus highly desired. We are now using several types of combinatorial peptide libraries to search for small size molecular mimetics that can interfere with the adhesion of bacteria to the target organ. The use of such peptides is expected to lead to the development of compounds for a novel preventive drug which does not kill bacteria, thus making it safer and less likely to generate drug-resistant mutants

サンカ ストレス ト シシュウビョウ

Periodontitis is a term used to describe a chronic inflammatory disease, caused by subgingival plaque biofilm, that leads to the loss of tissues supporting the root surfaces and adjacent alveolar bone, which ultimately results in tooth loss. It is believed that while the primary etiological agent is specific, a majority of periodontal tissue destruction is caused by an inappropriate host response to those microorganisms and their products. More specifically, a loss of homeostatic balance between reactive oxygen species (ROS) and antioxidant defense systems, which protect and repair vial tissues, cells, and molecular components, are believed to be responsible. A paradigm shift in our understanding of the importance of ROS and antioxidant power to human biology over the last decade came from the realization of vial and ubiquitous transcription factors. ROS are products of normal cellular metabolism; however, excessive products of ROS oxidize proteins, lipids, and DNA, resulting in tissue damage. Studies have shown that systemic increases in ROS are involved in the pathogenesis of periodontitis. When periodontitis develop, ROS produced in the periodontal lesion diffuse into the blood stream, resulting in the oxidation of circulating oxidative stress. For instance, previous animal studies in a rat periodontal model suggested that experimental periodontitis induced oxidative damage by increasing circulating oxidative stress. In addition, a positive association has been shown to exist between oxidative status and clinical attachment level in the maintenance phase of chronic periodontitis patients. These results suggest that high oxidative status in plasma could have affected the rate of progression of periodontal disease in the past. Furthermore, patients with chronic periodontitis showed higher levels of circulating oxidized low-density lipoproteins, C-reactive proteins, and oxidative stress than healthy subjects. Non-surgical periodontal treatment was effective in improving periodontal health and decreasing oxidized low-density lipoprotein and C-reactive protein, which were positively associated with a reduction in circulating oxidative stress. In patients with chronic periodontitis, a reduction in periodontal inflammation by non-surgical periodontal treatment might be beneficial in preventing systemic disease by decreasing circulating oxidative stress. Furthermore, increased serum levels of ROS following periodontitis may influence the rate of progression of systemic diseases. Hepatocellular carcinoma patients with chronic periodontitis had a higher circulating ROS level and progression of cancer than patients without periodontitis. Therefore, increased ROS levels following periodontitis may be detrimental to hepatic health

Applications of a novel biodetection system to saliva using protein fingerprints with data processing

A fundamental method has been developed focusing on a facile and rapid examination of periodontal disease. Periodontal disease is an oral disease thought to affect 80% of adults, and early detection with treatment is desirable for the improvement of the quality of life. Unfortunately conventional methods are not consistent as the disease is caused by a number of bacteria and detection relies on the skills of the dentist. Thus an objective detection system is required. We have performed an experiment on saliva using a novel biodetection system, designated PepTenChip®. A disease model for saliva was prepared using a specimen from a healthy subject and a mixture of hemoglobin (f-Hb) and lactate dehydrogenase (LDH), which is used as a periodontal disease marker protein with healthy saliva. PepTenChip® is a peptide microarray in which fluorescent labelled structured peptides are immobilized on a novel amorphous carbon substrate. Since the peptides used as capture molecules are fluorescently labelled, labeling of analytes is not necessary. The fluorescence intensity change before and after application of analytes are detected rather than the ON/OFF detection common to conventional microarrays using a set of antigen-antibody. The fluorescence intensity value changes according to the concentration of captured protein allowing the generation of protein fingerprint (PFP) and dendrograms. The present method does not rely on a "one to one" interaction, unlike conventional biodetection, and advantages can be envisaged in the case of an undefined or unknown cause of disease. The statistical analyses, such as multivariate analyses, allow classification of the type of proteins added in saliva as mimetics of disease. PepTenChip® system is useful and convenient for examination of periodontal disease in health care

Synthesis of Novel Phosphorus-Substituted Stable Isoindoles by a Three-Component Coupling Reaction of ortho-Phthalaldehyde, 9,10-Dihydro-9-oxa-10-phosphaphenanthrene 10-Oxide, and Primary Amines

A three-component coupling reaction of ortho-phthalaldehyde, 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide, and various primary amines readily afforded novel phosphorus-substituted stable isoindoles in good to excellent yields. The importance of the reversible ring-opening of 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide by methanolysis in the three-component coupling reaction became apparent

ヒト角化上皮細胞における5-FU誘発性酸化ストレスおよび炎症応答に対するresveratrolの保護効果

Although 5-fluorouracil (5-FU) is currently used as an anti-cancer chemotherapy, adverse effects such as oral mucositis potentially limit its clinical application. Additionally, the prevention of 5-FU-induced side effects are scarce. Resveratrol is known to decrease oxidative damage and inflammation. In this study, we examined the protective effects of resveratrol on 5-FU-induced oxidative stress and inflammatory responses in normal human keratinocytes (HaCaT cell) as in vitro oral mucositis model. HaCaT cells were exposed to 5-FU and simultaneously treated with resveratrol. The effects of resveratrol on 5-FU-induced cytotoxicity were evaluated using cell viability assay. The production of reactive oxygen species (ROS) was measured using a fluorescence spectrophotometer. The effects of resveratrol on nuclear factor erythroid 2-related factor 2 (Nrf2), silent information regulator transcript-1 (SIRT-1), and nuclear factor kappa B (NF-κB) signaling and inflammatory cytokine expression were examined. Resveratrol suppressed 5-FU-induced overproduction of ROS by upregulating anti-oxidant defense genes through Nrf2 activation and SIRT-1 expression. Concerning inflammatory responses, resveratrol suppressed the 5-FU-induced expression of pro-inflammatory cytokines via NF-κB nuclear translocation. Conversely, N-acetylcysteine reduced ROS levels without affecting the expression of pro-inflammatory cytokines. Resveratrol might be useful for preventing 5-FU-induced adverse effects by activating anti-oxidant and anti-inflammatory responses

Hydrogen-Rich Water Intake Accelerates Oral Palatal Wound Healing via Activation of the Nrf2/Antioxidant Defense Pathways in a Rat Model

The wound healing process attempts to restore the integrity and function of the injured tissue. Additionally, proinflammatory cytokines, growth factors, and oxidative stress play important roles in wound healing. The aim of this study was to determine whether hydrogen-rich water intake induces the activation of the Nrf2/antioxidant defense pathway in rat palatal tissue, thereby reducing systemic oxidative stress and proinflammatory cytokine levels and promoting healing-associated genes. A circular excisional wound was created in the oral palatal region, and the wound healing process was observed. The rats were divided into two experimental groups in which either hydrogen-rich water or distilled water was consumed. In the drinking hydrogen-rich water, the palatal wound healing process was accelerated compared to that in the control group. As molecular hydrogen upregulated the Nrf2 pathway, systemic oxidative stresses were decreased by the activation of antioxidant activity. Furthermore, hydrogen-rich water intake reduced proinflammatory cytokine levels and promoted the expression of healing-associated factors in rat palatal tissue. In conclusion, hydrogen-rich water intake exhibited multiple beneficial effects through activation of the Nrf2/antioxidant defense pathway. The results of this study support the hypothesis that oral administration of hydrogen-rich water benefits the wound healing process by decreasing oxidative stress and inflammatory responses

Hydrogen-Rich Water Intake Accelerates Oral Palatal Wound Healing via Activation of the Nrf2/Antioxidant Defense Pathways in a Rat Model

The wound healing process attempts to restore the integrity and function of the injured tissue. Additionally, proinflammatory cytokines, growth factors, and oxidative stress play important roles in wound healing. The aim of this study was to determine whether hydrogen-rich water intake induces the activation of the Nrf2/antioxidant defense pathway in rat palatal tissue, thereby reducing systemic oxidative stress and proinflammatory cytokine levels and promoting healing-associated genes. A circular excisional wound was created in the oral palatal region, and the wound healing process was observed.The rats were divided into two experimental groups in which either hydrogen-rich water or distilled water was consumed. In the drinking hydrogen-rich water, the palatal wound healing process was accelerated compared to that in the control group. As molecular hydrogen upregulated the Nrf2 pathway, systemic oxidative stresses were decreased by the activation of antioxidant activity. Furthermore, hydrogen-rich water intake reduced proinflammatory cytokine levels and promoted the expression of healing-associated factors in rat palatal tissue. In conclusion, hydrogen-rich water intake exhibited multiple beneficial effects through activation of the Nrf2/antioxidant defense pathway.The results of this study support the hypothesis that oral administration of hydrogen-rich water benefits the wound healing process by decreasing oxidative stress and inflammatory responses

ヒト歯肉線維芽細胞における酸化ストレスに対するレスベラトロール，ケルセチン，及びN-アセチルシステインの生物学的影響

In periodontitis, production of reactive oxygen species (ROS) by neutrophils induces oxidative stress and deteriorates surrounding tissues. Antioxidants reduce damage caused by ROS and are used to treat diseases involving oxidative stress. This study summarizes the different effects of resveratrol, quercetin, and N-acetylcysteine (NAC) on human gingival fibroblasts (HGFs) under oxidative stress induced by hydrogen peroxide. Real-time cytotoxicity analyses reveals that resveratrol and quercetin enhanced cell proliferation even under oxidative stress. Of the antioxidants tested, resveratrol is the most effective at inhibiting ROS production. HGFs incubated with resveratrol and quercetin up-regulate the transcription of type I collagen gene after 3 h, but only resveratrol sustained this up-regulation for 24 h. A measurement of the oxygen consumption rate (OCR, mitochondrial respiration) shows that resveratrol generates the highest maximal respiratory capacity, followed by quercetin and NAC. Simultaneous measurement of OCR and the extracellular acidification rate (non-mitochondrial respiration) reveals that resveratrol and quercetin induce an increase in mitochondrial respiration when compared with untreated cells. NAC treatment consumes less oxygen and enhances more non-mitochondrial respiration. In conclusion, resveratrol is the most effective antioxidant in terms of real-time cytotoxicity analysis, reduction of ROS production, and enhancement of type I collagen synthesis and mitochondrial respiration in HGFs