Inhibitory Effects of Standardized Boesenbergia pandurata Extract and Its Active Compound Panduratin A on Lipopolysaccharide-Induced Periodontal Inflammation and Alveolar Bone Loss in Rats.

Periodontitis, an inflammatory disease of the gingival tissue, triggered by microbial-derived elements, such as lipopolysaccharide (LPS), collapses the periodontal tissues and resorbs the alveolar bone. This study evaluated the inhibitory effects of standardized Boesenbergia pandurata extract (BPE) and panduratin A (PAN) on periodontitis-induced inflammation and alveolar bone loss. Sprague-Dawley rats with LPS-induced periodontitis were orally administered BPE (50 and 200 mg/kg/day) and PAN (20 mg/kg/day) for 8 days. Histological analysis revealed that BPE- and PAN-administered groups showed decreased cell infiltration and alveolar bone resorption. Furthermore, the BPE and PAN significantly alleviated the mRNA and protein expression levels of nuclear factor kappa B (NF-κB), interleukin-1ß, matrix metalloproteinase (MMP)-2, and MMP-8. BPE and PAN also inhibited the expression of nuclear factor of activated T cells, cytoplasmic 1, c-Fos, and ostoclastogenesis-related enzymes, including cathepsin K and tartrate-resistant acid phosphatase (ALP). BPE and PAN not only upregulated the osteoblastogenesis-associated markers, such as collagen type I (COL1A1) and ALP, but also increased the ratio of osteoprotegerin to receptor activator of NF-κB ligand. Collectively, BPE and PAN efficiently prevent destruction of periodontal tissues and stimulating the loss of alveolar bone tissues, strongly indicative of their potential as natural antiperiodontitis agents.

Effects of Geum urbanum L. root extracts and its constituents on polymorphonuclear leucocytes functions. Significance in periodontal diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Geum urbanum L. (wood avens) root infusions and decoctions have been used externally for reducing the bleeding and inflammation of gums (gingivitis), and mucous membranes. AIM OF THE STUDY: Taking into account that primed and hyperactivated neutrophils are an important factor in the transition from gingivitis to periodontitis, we investigated the effects of phytochemically characterised (HPLC-DAD-MS(n)) extracts of different polarity from Geum urbanum root on oxidative burst, elastase, metalloproteinase 9 (MMP-9), interleukin 8 (IL-8) and 1ß (IL-1ß), tumour necrosis factor (TNF-α) release, expression of adhesion molecules (CD62L and CD11b) and delayed apoptosis in stimulated neutrophils. As gemin A is a dominating compound in a raw material, so we considered its activity in parallel with the positive control quercetin. MATERIALS AND METHODS: The extracts were characterised by HPLC-DAD- MS(n) method. The inhibition of ROS production by stimulated neutrophils was determined using luminol dependent chemiluminescence method. The effect on MMP-9, IL-1ß, TNF-α and IL-8 production by neutrophils was measured by enzyme-linked immunosorbent assay (ELISA). Neutrophil elastase release was established spectrophotometrically. The expression of adhesion molecules and the apoptosis of neutrophils was analyzed with flow cytometry. RESULTS: The main compounds detected in the extract belong mainly to the group of ellagitannin: pedunculagin, stachyurin, casuarynin and gemin A, and ellagic acid derivatives. Procyanidins and one complex tannin were found as minor compounds. Gemin A significantly affected the functions of stimulated neutrophils by reducing the surface expression of CD11b, and inhibiting the release of reactive oxygen species, and proteases (elastase, MMP-9), chemokines and cytokines (interleukins IL-8, IL-1ß). Interestingly, gemin A stimulated the release of TNF-α, which may be one of the stimulators of apoptosis of neutrophil cells. The primary aqueous extract, the ethyl acetate and the butanolic fractions, all containing the highest level of gemin A, have exerted similar but weaker activity. CONCLUSION: The modulating effect on the neutrophils function of extracts, and its main constituent gemin A, support the traditional use of this plant material in cavity inflammation including mucositis, gingivitis and periodontosis.

Wild Blueberry (Vaccinium angustifolium Ait.) Polyphenols Target Fusobacterium nucleatum and the Host Inflammatory Response: Potential Innovative Molecules for Treating Periodontal Diseases.

Blueberries contain significant amounts of flavonoids to which a number of beneficial health effects in humans have been associated. The present study investigated the effect of a polyphenol-rich lowbush blueberry (Vaccinium angustifolium Ait.) extract on the two main etiologic components of periodontitis, a multifactorial disorder affecting the supporting structures of the teeth. Phenolic acids, flavonoids (flavonols, anthocyanins, flavan-3-ols), and procyanidins made up 16.6, 12.9, and 2.7% of the blueberry extract, respectively. The blueberry extract showed antibacterial activity (MIC = 1 mg/mL) against the periodontopathogenic bacterium Fusobacterium nucleatum. This property may result from the ability of blueberry polyphenols to chelate iron. Moreover, the blueberry extract at 62.5 µg/mL inhibited F. nucleatum biofilm formation by 87.5 ± 2.3%. Subsequently, the ability of the blueberry extract to inhibit the NF-κB signaling pathway in U937-3xκB cells was investigated. The blueberry extract dose-dependently inhibited the activation of NF-κB induced by F. nucleatum. In addition, a pretreatment of macrophages with the blueberry extract (62.5 µg/mL) inhibited the secretion of IL-1ß, TNF-α, and IL-6 by 87.3 ± 1.3, 80.7 ± 5.6, and 28.2 ± 9.3%, respectively, following a stimulation with F. nucleatum. Similarly, the secretion of MMP-8 and MMP-9 was also dose-dependently inhibited. This dual antibacterial and anti-inflammatory action of lowbush blueberry polyphenols suggests that they may be promising candidates for novel therapeutic agents.

O efeito adjunto de uma suplementação alimentar à base de ômega-3 no tratamento da periodontite: um estudo clínico e imunológico / The adjunctive effects of Omega-3 dietary supplementation in the treatment of periodontitis: a clinical and immunological study

O objetivo foi avaliar se a suplementação com ômega (ω)-3 no tratamento não cirúrgico da periodontite melhora os resultados clínicos e imunológicos. Avaliar os níveis séricos dos ω-3 e ω-6 na doença periodontal, investigar se o tratamento periodontal associado ou não a suplementação com ω-3 afeta os níveis séricos destes. Assim como avaliar a expressão de um painel de citocinas relacionadas a osteoclatogênese no fluido gengival (FG) de sítios dos pacientes com gengivite e periodontite, adicionalmente relacionar estas citocinas a densidade óptica do osso alveolar destes sítios. Por fim, investigar se as terapias propostas neste estudo afetam os parâmetros clínicos periodontais, a densidade óptica do osso alveolar e a expressão das citocinas no FG. Para isso foi realizado um ensaio clínico piloto, randomizado, duplo-cego, controlado-placebo, com vinte e um pacientes com periodontite e dezesseis com gengivite. Estes foram investigados para os níveis séricos dos ácidos graxos poli-insaturados de cadeia longa (AGPI-CL), ácido eicosapentaenóico (EPA), ácido docosahexaenóico (DHA), ácidos docosapentaenóico (DPA), o ácido araquidônico (AA) usando cromatografia gasosa. O FG dos sítios controle-gengivite, controle-periodontite e destruído de pacientes com periodontite foi avaliado para Receptor ativador do fator nuclear kappa-B ligante (RANK-L), osteoprotegerina (OPG), a osteocalcina (OC), fator de necrose tumoral (TNF)-α, interferon (IFN)-γ, interleucina (IL) -1ß, IL-4, IL-6 e IL-10, utilizando imunoensaio multiplex. Pacientes com periodontite foram subagrupados em grupos com e sem Síndrome Metabólica para avaliação dos AGPI-CL. Sítios dos pacientes com periodontite foram subagrupados em sítios sem e com considerável desmineralização ópticas baseado na avaliação da densidade óptica alveolar representada pelos valores de pixels das radiografias intraorais digitais para avaliação das citocinas no FG. Pacientes com periodontite foram randomizados em raspagem e alisamento radicular mais suplementação com ω-3 (RAR+ω-3) ou placebo (RAR+placebo), e foram reavaliados depois de quatro meses para AGPI-CL no soro, citocinas no FG e densidade alveolar óptica. Os níveis significativamente maiores dos AGPI-CLs foram observados em pacientes com periodontite em comparação com gengivite. A profundidade de bolsa mostrou uma correlação positiva significativa com DHA, DPA e AA. Após RAR+ω-3, DPA, AA, AA/EPA e AA/DHA reduziram significativamente, e depois da RAR+placebo todos os níveis dos AGPI-CLs reduziram significativamente. Os níveis das citocinas, IFN-γ, IL-4, IL-10, RANK-L e OC, no FG de sítios controle-gengivite foram menores comparados aos sítios controle-periodontite e destruído. O mesmo resultado foi observado para os níveis da IL-1ß, IL-6 e OPG em comparação com sítios destruídos. Pacientes com periodontite apresentaram níveis mais baixos de IL-1ß e OPG em sítios controle-periodontite comparado aos destruídos. Após RAR+ω-3, o nível da IL-4 aumentou e os níveis de OC, IFN-γ e IL-10 diminuíram. Não houve diferenças significativas entre os grupos experimentais para a densidade alveolar óptica e parâmetros. Em conclusão, os níveis séricos dos AGPI-CLs são afetados pela gravidade de doença periodontal e diferem com a presença da síndrome metabólica. Citocinas relacionadas a osteoclatogênese no FG refletem a gravidade periodontal e diferem com densidade óptica alveolar alterada. A suplementação com ω-3 não melhora clinica ou imunologicamente o resultado do tratamento periodontal.

The aim was to test whether omega (ω)-3 supplementation associated to non-surgical treatment of periodontitis improves clinical and immunological results. Evaluate the serum levels of ω-3 and ω-6 in periodontal disease, hence, to investigate whether periodontal treatment with or without ω-3 supplementation affects serum levels of these. Therefore, to evaluate the expression of a panel of cytokines related to osteoclastogenesis in the gingival crevicular fluid (GCF) sites of patients with gingivitis and periodontitis, additionally relate these cytokines with optical alveolar bone density in these sites. Finally, to investigate whether the therapies proposed in this study affect the clinical periodontal parameter, the optical density of the alveolar bone and the expression of cytokines in GCF. Then was conducted a pilot clinical trial, randomized, double-blind, placebo-controlled, with twenty-one patients with periodontitis and sixteen with gingivitis. These were investigated for blood levels of long chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), arachidonic acid (AA) using gas chromatography. The GCF of the sites of control-gingivitis, control-periodontitis and destroyed from patients periodontitis were evaluated for receptor activator of kappa-B ligand nuclear factor (RANK-L), osteoprotegerin (OPG), osteocalcin (OC), tumor necrosis factor (TNF) -α, interferon (IFN) -γ, interleukin (IL) -1ß, IL-4, IL-6 and IL-10 using multiplex immunoassay. Patients with periodontitis were subgrouped in groups with and without metabolic syndrome to evaluate the LC-PUFA. Sites of patients with periodontitis were subgrouped at sites with and without considerable optical demineralization based on the evaluation of alveolar optical density represented by the pixel values of the digital intraoral radiographs for evaluation of cytokines in GCF. Patients were randomized into the periodontal scaling and root planing more ω-3 supplementation (ω-3 SRP +) or placebo (SRP + placebo), and were assessed after four months to LC-PUFA in serum, cytokines in GCF and alveolar optical density. The significantly higher levels of LC-PUFA were observed in patients with periodontitis compared to gingivitis. The pocket depth showed a significant positive correlation with DHA, DPA and AA. After RAR + ω-3, APD, AA, AA / AA and EPA / DHA reduced significantly, and, after SRP + placebo, all levels of LC-PUFA reduced significantly. The levels of cytokines, IFN-γ, IL-4, IL-10, and OC RANK-L, from controlgingivitis sites GCF were lower compared to control-periodontitis and destroyed sites. The same result was observed for levels of IL-1ß, IL-6 and OPG compared to destroyed sites. Periodontitis patients had lower levels of IL-1ß and OPG in control-periodontitis compared to destroyed sites. After SRP + ω-3, the level of IL-4 and OC increased and levels of IFN-γ and IL-10 decreased. There were no significant differences between the experimental groups to optical density and clinical parameters. In conclusion, serum levels of LC-PUFA are affected by periodontal disease severity and differ in the presence of the metabolic syndrome. Cytokines related to osteoclastogenesis in GCF reflect the periodontal severity and differ with impaired alveolar optical density. Ω-3 supplementation does not improve clinical or immune result of non-surgical periodontal treatment.

Prescribing for periodontal disease.

With concerns about the ever-increasing development of antimicrobial resistance, it is imperative that antimicrobials are prescribed responsibly and used appropriately. This article provides an overview and simple guidelines for antimicrobial prescribing in the management of periodontal diseases.

The plant coumarins auraptene and lacinartin as potential multifunctional therapeutic agents for treating periodontal disease.

BACKGROUND: Periodontal diseases are bacterial infections leading to chronic inflammation disorders that are frequently observed in adults. In the present study, we evaluated the effect of auraptene and lacinartin, two natural oxyprenylated coumarins, on the growth, adherence properties, and collagenase activity of Porphyromonas gingivalis. We also investigated the capacity of these compounds to reduce cytokine and matrix metalloproteinase (MMP) secretion by lipopolysaccharide (LPS)-stimulated macrophages and to inhibit MMP-9 activity. METHODS: Microplate dilution assays were performed to determine the effect of auraptene and lacinartin on P. gingivalis growth as well as biofilm formation stained with crystal violet. Adhesion of FITC-labeled P. gingivalis to oral epithelial cells was monitored by fluorometry. The effects of auraptene and lacinartin on LPS-induced cytokine and MMP secretion by macrophages were determined by immunological assays. Fluorogenic assays were used to evaluate the capacity of the two coumarins to inhibit the activity of P. gingivalis collagenase and MMP-9. RESULTS: Only lacinartin completely inhibited P. gingivalis growth in a complex culture medium. However, under iron-limiting conditions, auraptene and lacinartin both inhibited the growth of P. gingivalis. Lacinartin also inhibited biofilm formation by P. gingivalis and promoted biofilm desorption. Both compounds prevented the adherence of P. gingivalis to oral epithelial cells, dose-dependently reduced the secretion of cytokines (IL-8 and TNF-α) and MMP-8 and MMP-9 by LPS-stimulated macrophages, and inhibited MMP-9 activity. Lacinartin also inhibited P. gingivalis collagenase activity. CONCLUSIONS: By acting on multiple targets, including pathogenic bacteria, tissue-destructive enzymes, and the host inflammatory response, auraptene and lacinartin may be promising natural compounds for preventing and treating periodontal diseases.

Black tea polyphenol inhibits CXCL10 production in oncostatin M-stimulated human gingival fibroblasts.

CXC chemokine ligand 10 (CXCL10) plays an important role in the infiltration of Th1 cells and thus in the exacerbation of periodontal disease. Theaflavin-3,3'-digallate (TFDG), polyphenol in black tea, has some beneficial effects but the effect of TFDG on CXCL10 production from human gingival fibroblasts (HGFs) is uncertain. In this study, we investigated the mechanisms by which TFDG may inhibit oncostatin M (OSM)-induced CXCL10 production in human gingival fibroblasts. TFDG prevented OSM-mediated CXCL10 production by HGFs in a dose dependent manner. TFDG significantly inhibited OSM-induced phosphorylation of c-Jun N terminal kinase (JNK), protein kinase B (Akt) (Ser473) that are related to CXCL10 production from OSM-stimulated HGFs. In addition, TFDG suppressed OSM receptor (OSMR) ß expression on HGFs. These data provide a novel mechanism where the black tea flavonoid, theaflavin, could provide direct benefits in periodontal disease.

A review of the critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D deficiency.

This review looks at the critical role of vitamin D in improving barrier function, production of antimicrobial peptides including cathelicidin and some defensins, and immune modulation. The function of vitamin D in the innate immune system and in the epithelial cells of the oral cavity, lung, gastrointestinal system, genito-urinary system, skin and surface of the eye is discussed. Clinical conditions are reviewed where vitamin D may play a role in the prevention of infections or where it may be used as primary or adjuvant treatment for viral, bacterial and fungal infections. Several conditions such as tuberculosis, psoriasis, eczema, Crohn's disease, chest infections, wound infections, influenza, urinary tract infections, eye infections and wound healing may benefit from adequate circulating 25(OH)D as substrate. Clinical diseases are presented in which optimization of 25(OH)D levels may benefit or cause harm according to present day knowledge. The safety of using larger doses of vitamin D in various clinical settings is discussed.

[Effectiveness of chronic periodontal disease treatment by infrared laser light].

Thirty-six patients with light and moderate chronic periodontal disease (CPD) were included in the study. The patients were divided in two groups according to treatment options: first group (18 patients) received conventional periodontal treatment, second (18 patients) - in addition to conventional treatment were treated by phototherapy (infrared laser light). Control group included 10 persons with no signs of periodontal disease. Treatment effectiveness was assessed by local cytokine profile (IL-1ß, IL-1ra, IL-6, IL-10, TNF-α, OPG and RANKL). Increased level of inflammatory cytokines TNF-α, IL-1ß, IL-6 confirmed pronounced inflammation in periodontal tissues in CPD patients. OPG level was lower than in control group while RANKL level increased significantly. After treatment in both CРD groups TNF-α and IL-6 decrease was observed, IL-1ß (had not changed. In the second group RANKL level also decreased dramatically - 6.7-fold compared to its values before treatment.

Anti-neutrophil cytoplasmic autoantibodies: a renewed paradigm in periodontal disease pathogenesis?

In the past, various models including the autoimmunity model have been proposed to explain the pathogenesis of periodontal diseases. The aim of this review is to introduce the pathogenic role of anti-neutrophil cytoplasmic autoantibodies (ANCAs) in various autoimmune diseases and compare these conditions with periodontal disease to elucidate common pathogenic mechanisms. Also, a novel model to explain the pathogenesis of periodontal disease based on the concept of ANCA-associated autoimmunity is proposed. This encompasses a wide array of biochemical mediators that range from direct and indirect initiators of ANCA production and eventual release of proinflammatory mediators and free radicals, all of which have been implicated in periodontal tissue destruction in the past. In addition, specific links between the typical ANCA-associated diseases and periodontal disease are discussed. Finally, a new paradigm in the periodontal disease-associated destruction is proposed that includes the currently accepted mechanism, namely, the genetic-microbial-host interactions.

Evaluación clínica, microbiológica e inmuológica de la ozonoterapia en pacientes con bolsas periodontales moderadas-severas / Clinical, microbiological and inmunological evaluation of the ozone's therapy in patients with moderate-severe periodontal pockets

Introducción. En los últimos años se ha producido un progreso importante en el conocimiento de la enfermedad periodontal, desde su etiología multifactorial, la microbiología responsable, la respuesta imunológica local, así como múltiples aspectos en relación con su epidemiología, etiopatogenia y su proceso evolutivo. Dado el mayor conocimiento en estos campos, se desarrollan nuevas técnicas, productos farmacológicos y técnicas que tratan de detener la enfermedad periodontal y preservar la salud bucal. Objetivos. Analizar las respuestas periodontales desde un punto de vista clínico, microbiológico e inmunológico de una población con bolsas periodontales moderadas severas y su comparación, tras la ozonoterapia, con la técnica del raspado y alisado radicular. Material y método. Se estudiaron un total de 72 cuadrantes maxilares con al menos >4dientes en dichos cuadrantes y >6mm de profundidad de sondaje (bolsa periodontal moderada-severa) en una población con una media de edad de 43 años. Para establecer las comparaciones entre ambos grupos se realizó un estudio a boca partida en el que la mitad de los cuadrantes fueron tratados con ozono y la otra restante con una técnica de raspado y alisado radicular. Se evaluaron las variables respuestas: clínico-microbiológico e inmunológico mediante análisis estadísticos descriptivo y anova. Conclusión. Podemos establecer de forma preliminar, que el tratamiento periodontal con ozono (primologo3) produce una reducción estadísticamente significativa en el índice de sangrado gingival de lindhe, en la microbiología patógena periodontal así como de los patrones inmunológicos de la ikl-b y el tnf-alfa, sin embargo no produce variación alguna en relación al nivel de inserción periodontal y de la profundidad de la bolsa periodontal que requiere su remoción mecánica con el raspado y alisado radicular. Asimismo se requiere de un mayor número de estudios que corroboren estos hallazgos (AU)

Introduction. In recent years, important progress has be en made in the knowledge of periodontal disease, from a multifactorial etiology, the responsable microbiology, the local inmunological response as also multiple aspects related to its epidemiology, etiology and its evolution. Given a greater knowledge in thsese fields new techniques (pharmacological products and apparatus) are being developed to treat and detain the periodontal disease and preserve dental health. Objectives. Analyse the periodontal response from a clinical, microbiological and immunological point of view of a population with moderate-severe periodontal pockets and its comparison with the scraping and smoothing periodontal technique. Method and matlrial. A total of 72 cuadrants with at least more than four teeth in each cuadrant and more than 6mm.pocket depth probe were studied in a population of 43 average age. Toestablish comparison between both groups a cross mouth study has been done, in which half were treated with ozone and the rest with scraping technique. The variable results were evaluated: clinical, microbiological and immunological response with descriptive estadistic analysis and anova. Conclusion: we can say that the periodontal treatment with ozone produces estadisticaly significant reduction in the amount of index gingival bleeding, in the microbiological periodontal parameters as also in the immunological patterns of il1b y tnf-alfa, however there is no variation in relation to the level periodon tal insertion and the depth of the periodontal pocket that requires a periodontal technique of scraping (AU)

Psychoneuroimmunology: new avenues of research for the twenty-first century.

Psychoneuroimmunology (PNI) investigates the relations between the psychophysiological and immunophysiological dimensions of living beings. PNI brings together researchers in a number of scientific and medical disciplines, including psychology, the neurosciences, immunology, physiology, pharmacology, psychiatry, behavioral medicine, infectious diseases, and rheumatology. All are scientists with profound interest in interactions between the nervous and immune systems, and the relation between behavior and health. Despite the variety in domains and approaches to research, the outcome common to all research endeavors is the discovery of new information, of uncovered facts, of novel evidence, which contributes to the continuing generation of knowledge. In this paper we discuss psychoneuroimmune aspects of some conditions that are not routinely immediately associated with immunity, such as the condition of being the caregiver of somebody suffering from dementia; the effect on the brain-body modulations of aluminum, a metal that is not a component of the human body; and insomnia, a fairly common but disturbing disease, that even today lacks an effectual treatment.

[The effect of magnetotherapy on the immunobiochemical indices of subjects with diseases of the periodontal tissues and joints]. / Vliianie magnitoterapii na immunobiokhimicheskie pokazateli u lits s zabolevaniiami tkanei parodonta i sustavov.

Kept under medical surveillance in a health resort setting were 52 patients with disorders of the parodontium and large joints. All patients were given a complex therapy involving dietotherapy, therapeutic exercise, hydrotherapy, mud-treatment. Those patients having parodontium diseases were also prescribed topical treatment (chloride-sodium mouth baths and mud applications to the gingiva area). The main group subjects were also exposed to VMF using the unit for low-frequency therapy "Gradient-1". Laboratory means were also made use of, as a complex of biochemical tests characterizing changes in lipid metabolism. The level of the natural bodily resistance was determined by nitroblue tetrazolium test (NBT-test). The condition of the parodontium was evaluated by the Loë-Silness index. Adaptive reactions were studied by the lymphocytes-to-segmented neutrophils ratio. Adoption of therapy involving physiobalneofactors in patients with afflictions of the parodontium tissues and large joints makes for development of favourable in prognostic respect adaptive reactions.

Oral conditions in individuals with selective immunoglobulin A deficiency and common variable immunodeficiency.

Saliva and serum samples were collected from 36 individuals with selective immunoglobulin A deficiency (IgAd) and 23 patients with common variable immunodeficiency (CVI). The oral examination included registration of the teeth, Russell's periodontal index (PI), pocket formation, and salivary flow rate in both unstimulated and stimulated saliva. No differences were found in salivary flow rate, number of teeth, or pocket depth when donors with IgAd or CVI were compared to age and sex matched controls. However, mucosal manifestations of lichenoid type were more frequent in both types of immunoglobulin deficient individuals. An increased PI was also seen in CVI patients. Increased serum IgG and salivary IgM levels were found in the IgAd population.

Controversies, perspectives, and clinical implications of nutrition in periodontal disease.

Many controversies concerning the role of nutrition in periodontal disease and problems in the design and analysis of nutrition-periodontal disease studies have been reviewed. In addition, recent advances in the interactions of nutrition, host defense, and infection have been conceptually related to the pathogenesis of periodontal disease. Finally, nutritional factors relevant to the diagnosis and clinical management of patients with periodontal disease have been discussed. The concepts developed with respect to experimental design and the host defenses approach to periodontal disease, will hopefully serve to encourage definitive studies which may delineate a more precise role for nutrition in periodontal disease.