UKY DENTAL COBRE: POLYBACTERIAL PERIODONTITIS: N-3 PUFA AND ANTIOXIDANTS

UKY DENTAL COBRE：多细菌牙周炎：N-3 PUFA 和抗氧化剂

• 批准号: 7382116
• 负责人: Kesavalu Naidu Lakshmyya
• 金额: $ 7.16万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382116
• 关键词: UKY; DENTAL; COBRE; POLYBACTERIAL; PERIODONTITIS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The original Project 3 focused on polymicrobial infections inducing inflammation and bone loss using a murine calvarial model. It was designed to examine synergistic virulence effects of P. gingivalis, T. forsythensis, and T. denticola. Additionally, the aims were developed to determine the impact of acquired immune responses to infection and active immunity following immunization of the inflammation and tissue destruction. Following submission of the COBRE and prior to its funding in Sept. 2004, this research was funded as an R01 from the NIDCR. Thus, the COBRE grant provided the PI, Dr. Kesavalu, a ?Transition Award? to extend his research and contribute to submission of a 2nd R01 application. The funding provided support for a pilot study, initiated to document the ability to infect the oral cavity of rats with the polymicrobial consortium of P. gingivalis (Pg), T. denticola (Td), and T. forsythia (Tf) (Pg/Td/Tf). This was compared to the potential that incorporation of F. nucleatum (bridging and coaggregating pathogen) into this mixture (Pg/Td/Tf/Fn) would enhance the effectiveness of the infection regimen. Using an modified infection procedure, rats were challenged orally on 5 consecutive days with a 2% CMC solution containing a mixture of the microorganisms. The molar teeth were swabbed, DNA isolated from oral samples, and assessed using PCR for the presence of the bacteria. The results demonstrated seminal data that the rats were infected with the polymicrobial pathogenic consortia. Rats were euthanized, the gingival tissues collected and snap frozen in liquid nitrogen. Blood and rat jaws also were collected for serum IgG antibody and assessment of alveolar bone resorption. A significant serum antibody response to members of the polymicrobial infection was noted, supporting oral tissue infection and systemic challenge by the oral infection. Interestingly, the polymicrobial challenge with the Pg/Td/Tf/Fn consortium (5 days, 1 time during the 12 weeks), appeared to elicited substantially greater antibody. Alveolar bone loss in rats infected with these consortia demonstrated 2 primary findings. The single infection regimen with the Pg/Td/Tf challenged elicited minimal bone loss, supporting that a single challenge regimen is not sufficient to establish and maintain a disease process. However, the Pg/Td/Tf/Fn consortium, with a minimal infection challenge, induced significant bone loss, that was significantly greater than noted with any of the monoinfections, which had received the challenge multiple times during the 12 weeks. These findings provided additional preliminary data in support of an R01 application that is currently under review at the NIH. The aims of this proposal include: SPECIFIC AIM 1: To determine the effect of n-3 PUFA to modulate periodontal inflammation and alveolar bone loss induced by the pathogenic consortium P. gingivalis-T. forsythia-T. denticola in rats. SPECIFIC AIM 2. To determine the effect of a dietary antioxidant supplement ?-lipoic acid and vitamin E (?-LA/VE) to modulate periodontal inflammation and alveolar bone loss induced by the pathogenic consortium P. gingivalis, T. forsythia, and T. denticola in rats. SPECIFIC AIM 3. To determine the effect of a potent anti-inflammatory/antioxidant natural dietary substance, curcumin, to modulate periodontal inflammation and alveolar bone loss induced by the pathogenic consortium P. gingivalis, T. forsythia, and T. denticola in rats. SPECIFIC AIM 4. To determine the effect of combinations of dietary anti-inflammatories/antioxidants as co-supplements to modulate or decrease periodontal inflammation and alveolar bone loss induced by the pathogenic consortium P. gingivalis, T. forsythia, and T. denticola in rats.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。原始项目3的重点是使用鼠校友模型诱导炎症和骨质流失的多数感染。它旨在检查牙龈疟原虫，T。Forsythensis和T. denticola的协同毒力作用。此外，开发了目的是确定炎症和组织破坏后，获得的免疫反应对感染和主动免疫的影响。在2004年9月的山毛上提交并在其资助之前提交后，这项研究是从NIDCR资助的。因此，毛刺赠款提供了PI，Kesavalu博士，“过渡奖？扩展他的研究并有助于提交第二R01申请。这笔资金为一项试验研究提供了支持，该研究旨在记录用牙龈疟原虫多粒子联盟（PG），T。Denticola（TD）和T. Forsythia（TF）感染大鼠口腔口腔的能力（PG/TD/TF）。将其与将F. nucleatum（桥接和凝集病原体）掺入该混合物（PG/TD/TF/FN）的潜力将增强感染方案的有效性。使用改良的感染程序，将大鼠连续5天用2％CMC溶液口服挑战，其中包含微生物的混合物。将摩尔齿擦拭，从口服样品中分离出DNA，并使用PCR评估细菌的存在。结果表明，开创性数据表明大鼠被多粒性病原体结合了。将大鼠安乐死，收集的牙龈组织并在液氮中捕获冷冻。还收集了血液和大鼠颌骨的血清IgG抗体和肺泡骨吸收的评估。注意到对多数菌感染成员的显着血清抗体反应，从而支持口腔感染和全身性挑战。有趣的是，与PG/TD/TF/FN联盟（在12周内的5天，1次）中，多数型挑战似乎引起了更大的抗体。感染这些财团的大鼠的牙槽骨质流失表现出2个主要发现。具有PG/TD/TF的单一感染方案提出了最小的骨质流失，支持单个挑战方案不足以建立和维持疾病过程。但是，PG/TD/TF/FN财团的感染挑战很小，引起了显着的骨质流失，这比任何单一感染都明显要大得多，在12周内，这已经多次受到挑战。这些发现提供了其他初步数据，以支持NIH目前正在审查的R01应用程序。该提案的目的包括：特定目的1：确定N-3 PUFA对调节牙周炎症和致病联盟诱导的牙槽骨质流失的影响。 Forsythia-t。大鼠的牙齿牙齿。具体目的2。确定饮食中抗氧化剂补充剂的作用？脂蛋白酸和维生素E（？-LA/VE），以调节牙周财团，T。forsythia和T. denticola诱导的牙周炎症和牙齿骨损失。具体目的3。确定有效的抗炎/抗氧化剂天然饮食物质姜黄素的作用，以调节牙周财团诱发的牙周炎症和牙性骨骼损失。具体目的4。确定饮食抗炎药/抗氧化剂的组合作为共同供应的影响，以调节或减少牙周炎症和牙槽联盟诱发的牙周炎症和肺泡骨损失，伴随着大鼠的Forsythia和T. denticola。