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Ashique S, Hussain A, Khan T, Pal S, Rihan M, Farid A, Webster TJ, Hassan MZ, Asiri YI. Insights into Intra Periodontal Pocket Pathogenesis, Treatment, In Vitro-In Vivo Models, Products and Patents, Challenges and Opportunity. AAPS PharmSciTech 2024; 25:121. [PMID: 38816555 DOI: 10.1208/s12249-024-02842-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Accepted: 05/15/2024] [Indexed: 06/01/2024] Open
Abstract
Periodontal disease is a multifactorial pathogenic condition involving microbial infection, inflammation, and various systemic complications. Here, a systematic and comprehensive review discussing key-points such as the pros and cons of conventional methods, new advancements, challenges, patents and products, and future prospects is presented. A systematic review process was adopted here by using the following keywords: periodontal diseases, pathogenesis, models, patents, challenges, recent developments, and 3-D printing scaffolds. Search engines used were "google scholar", "web of science", "scopus", and "pubmed", along with textbooks published over the last few decades. A thorough study of the published data rendered an accurate and deep understanding of periodontal diseases, the gap of research so far, and future opportunities. Formulation scientists and doctors need to be interconnected for a better understanding of the disease to prescribe a quality product. Moreover, prime challenges (such as a lack of a vital testing model, scarcity of clinical and preclinical data, products allowing for high drug access to deeper tissue regions for prolonged residence, lack of an international monitoring body, lack of 4D or time controlled scaffolds, and lack of successful AI based tools) exist that must be addressed for designing new quality products. Generally, several products have been commercialized to treat periodontal diseases with certain limitations. Various strategic approaches have been attempted to target certain delivery regions, maximize residence time, improve efficacy, and reduce toxicity. Conclusively, the current review summarizes valuable information for researchers and healthcare professional to treat a wide range of periodontal diseases.
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Affiliation(s)
- Sumel Ashique
- Department of Pharmaceutics, School of Pharmacy, Bharat Institute of Technology (BIT), Meerut, 250103, UP, India
| | - Afzal Hussain
- Department of Pharmaceutics, College of Pharmacy, King Saud University, 11451, Riyadh, Saudi Arabia.
| | - Tasneem Khan
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India
| | - Sejuti Pal
- School of Pharmacy, College of Health and Medicine, University of Tasmania, Churchill Ave, Sandybay, Hobart, TAS- 7005, Australia
| | - Mohd Rihan
- Department of Pharmacology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, 160062, India
| | - Arshad Farid
- Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan, 29050, Pakistan
| | - Thomas J Webster
- Division of Pre-college and Undergraduate Studies, Brown University, Providence, Rhode Island, 02912, USA.
| | - Mohd Zaheen Hassan
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Asir, Saudi Arabia
| | - Yahya I Asiri
- Department of Pharmacology, College of Pharmacy, King Khalid University, Asiri, Saudi Arabia
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Sufaru IG, Teslaru S, Pasarin L, Iovan G, Stoleriu S, Solomon SM. Host Response Modulation Therapy in the Diabetes Mellitus—Periodontitis Conjuncture: A Narrative Review. Pharmaceutics 2022; 14:pharmaceutics14081728. [PMID: 36015357 PMCID: PMC9414216 DOI: 10.3390/pharmaceutics14081728] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/12/2022] [Accepted: 08/17/2022] [Indexed: 11/30/2022] Open
Abstract
The inflammatory response of the host in periodontitis is the phenomenon that underlies the onset and evolution of periodontal destructive phenomena. A number of systemic factors, such as diabetes mellitus (DM), can negatively affect the patient with periodontitis, just as the periodontal disease can aggravate the status of the DM patient. Host response modulation therapy involves the use of anti-inflammatory and anti-oxidant products aimed at resolving inflammation, stopping destructive processes, and promoting periodontal healing, all important aspects in patients with high tissue loss rates, such as diabetic patients. This paper reviews the data available in the literature on the relationship between DM and periodontitis, the main substances modulating the inflammatory response (nonsteroidal anti-inflammatory drugs, sub-antimicrobial doses of doxycycline, or omega-3 fatty acids and their products, specialized pro-resolving mediators), as well as their application in diabetic patients.
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Affiliation(s)
- Irina-Georgeta Sufaru
- Department of Periodontology, Grigore T. Popa University of Medicine and Pharmacy, Universitatii Street 16, 700115 Iasi, Romania
| | - Silvia Teslaru
- Department of Periodontology, Grigore T. Popa University of Medicine and Pharmacy, Universitatii Street 16, 700115 Iasi, Romania
- Correspondence: (S.T.); (L.P.)
| | - Liliana Pasarin
- Department of Periodontology, Grigore T. Popa University of Medicine and Pharmacy, Universitatii Street 16, 700115 Iasi, Romania
- Correspondence: (S.T.); (L.P.)
| | - Gianina Iovan
- Department of Cariology and Restorative Dental Therapy, Grigore T. Popa University of Medicine and Pharmacy, Universitatii Street 16, 700115 Iasi, Romania
| | - Simona Stoleriu
- Department of Cariology and Restorative Dental Therapy, Grigore T. Popa University of Medicine and Pharmacy, Universitatii Street 16, 700115 Iasi, Romania
| | - Sorina Mihaela Solomon
- Department of Periodontology, Grigore T. Popa University of Medicine and Pharmacy, Universitatii Street 16, 700115 Iasi, Romania
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Bezerra B, Monajemzadeh S, Silva D, Pirih FQ. Modulating the Immune Response in Periodontitis. FRONTIERS IN DENTAL MEDICINE 2022. [DOI: 10.3389/fdmed.2022.879131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Periodontitis is a chronic inflammatory condition initiated by the accumulation of bacterial biofilm. It is highly prevalent and when left untreated can lead to tooth loss. The presence of bacterial biofilm is essential for the initiation of the inflammatory response but is not the sole initiator. Currently it is unknown which mechanisms drive the dysbiosis of the bacterial biofilm leading to the dysregulation of the inflammatory response. Other players in this equation include environmental, systemic, and genetic factors which can play a role in exacerbating the inflammatory response. Treatment of periodontal disease consists of removal of the bacterial biofilm with the goal of resolving the inflammatory response; however, this does not occur in every case. Understanding the way the inflammatory response does not return to a state of homeostasis has led investigators to consider both systemic and local pharmacological interventions. Nonetheless, a better understanding of the impact that genetics and environmental factors may have on the inflammatory response could be key to helping identify how inflammation can be modulated therefore stopping the destruction of the periodontium. In this article, we will explore the current evidence associating the microbial dysbiosis and the dysregulation of the immune response, potential mechanisms or pathways that may be targeted for the modulation of the inflammatory response, and discuss the advantages and drawbacks associated with local and systemic inflammatory modulation in the management of periodontal disease. This information will be valuable for those interested in understanding potential adjunct methods for managing periodontal diseases, but not limited to, dental professionals, clinical researchers and the public at large.
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Van Dyke TE. Shifting the paradigm from inhibitors of inflammation to resolvers of inflammation in periodontitis. J Periodontol 2020; 91 Suppl 1:S19-S25. [PMID: 32441774 PMCID: PMC8142079 DOI: 10.1002/jper.20-0088] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 03/17/2020] [Accepted: 03/30/2020] [Indexed: 12/24/2022]
Abstract
An initial shift in our understanding of the basis of periodontal disease occurred early in the 2000s. The host response, rather than the bacterial burden, was the principal determinant of the disease. Microbial dysbiosis that occurs in periodontal disease results from a hyperinflammatory state in the host. A second shift in periodontal disease is taking place. This time in the realm of treatment strategies. Rather than targeting antimicrobials or inhibitors of individual inflammatory mediators, preclinical studies support using resolution pharmacology to convert the pro-inflammatory condition into a non-inflammatory one, thereby resolving both the local and systemic inflammation associated with periodontal disease. Here, I describe the bases for these shifts in paradigms.
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Affiliation(s)
- Thomas E. Van Dyke
- Clinical and Translational Research, Forsyth Institute, Cambridge, MA
- Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA
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Polak D, Martin C, Sanz-Sánchez I, Beyth N, Shapira L. Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies? A systematic review. J Clin Periodontol 2015; 42 Suppl 16:S139-51. [DOI: 10.1111/jcpe.12340] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/25/2014] [Indexed: 02/02/2023]
Affiliation(s)
- David Polak
- Department of Periodontology; Hebrew University-Hadassah Faculty of Dental Medicine; Jerusalem Israel
| | - Conchita Martin
- Department of Stomatology IV; Area of Orthodontics; Complutense University of Madrid; Madrid Spain
| | - Ignacio Sanz-Sánchez
- Department of Stomatology; Area of Periodontics; Complutense University of Madrid; Madrid Spain
| | - Nurit Beyth
- Department of Prosthodontics; Hebrew University-Hadassah Faculty of Dental Medicine; Jerusalem Isreal
| | - Lior Shapira
- Department of Periodontology; Hebrew University-Hadassah Faculty of Dental Medicine; Jerusalem Israel
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Bhansali RS. Non-surgical periodontal therapy: An update on current evidence. World J Stomatol 2014; 3:38-51. [DOI: 10.5321/wjs.v3.i4.38] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Revised: 11/06/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
Periodontal disease is an inflammatory condition that involves a complex interaction between pathogenic bacteria, environmental and acquired factors and host related factors. Till recently periodontal treatment was directed primarily towards reduction of bacterial load by subgingival debridement of root surfaces and modification of environmental risk factors. The current paradigm of periodontal disease stresses greater role of host-mediated inflammatory response in tissue destruction characteristic of periodontal disease. Various therapeutic modalities have been developed adjuvant to mechanical periodontal therapy. The use of laser and photodynamic therapy show great promise but their effectiveness has still not been conclusively proven. Chemotherapeutic agents, either systemic and local antimicrobials or host modulating drugs, played pivotal role in better and more predictable management of periodontal disease. The present review focuses on the best available evidence, for the current management of the chronic periodontal patients, gathered from systematic reviews and meta-analysis of mechanical non surgical periodontal therapy (NSPT) (subgingival debridement, laser therapy and photodynamic therapy) and the adjunctive chemotherapeutic approaches such as systematic and local antibiotics and antiseptics, subgingival pocket irrigation and host modulation therapies. The review also attempts to briefly introduce future developments in some of these modalities. At the end, the review summarizes the analysis of the current evidence that suggests that thorough subgingival debridement remains the mainstay of NSPT and that adjunct use of chemotherapeutic agents may offer better management of clinical parameters in periodontitis patients.
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Gulati M, Anand V, Govila V, Jain N. Host modulation therapy: An indispensable part of perioceutics. J Indian Soc Periodontol 2014; 18:282-8. [PMID: 25024538 PMCID: PMC4095617 DOI: 10.4103/0972-124x.134559] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2013] [Accepted: 10/29/2013] [Indexed: 11/04/2022] Open
Abstract
Traditionally, only antimicrobials have been used as the chemotherapeutic modality for the treatment of periodontitis. Though bacteria are the primary etiologic factors of periodontal diseases, yet the extent and severity of tissue destruction seen in periodontitis is determined by the host immuno-inflammatory response to these bacteria. This increasing awareness and knowledge of the host-microbial interaction in periodontal pathogenesis has presented the opportunity for exploring new therapeutic strategies for periodontitis by means of targeting host response via host-modulating agents. This has lead to the emergence of the field of "Perioceutics" i.e. the use of parmacotherapeutic agents including antimicrobial therapy as well as host modulatory therapy for the management of periodontitis. These host-modulating agents used as an adjunct tip the balance between periodontal health and disease progression in the direction of a healing response. In this article the host-modulating role of various systemically and locally delivered perioceutic agents will be reviewed.
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Affiliation(s)
- Minkle Gulati
- Department of Periodontics, Babu Banarasi Das College of Dental Sciences, Babu Banarasi Das University, Lucknow, India
| | - Vishal Anand
- Department of Periodontics, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India
| | - Vivek Govila
- Department of Periodontics, Babu Banarasi Das College of Dental Sciences, Babu Banarasi Das University, Lucknow, India
| | - Nikil Jain
- Department of Oral and Maxillofacial Surgery, Vinayaka Missions Sankarachariyar Dental College, Salem, Tamil Nadu, India
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Gilhotra RM, Ikram M, Srivastava S, Gilhotra N. A clinical perspective on mucoadhesive buccal drug delivery systems. J Biomed Res 2013; 28:81-97. [PMID: 24683406 PMCID: PMC3968279 DOI: 10.7555/jbr.27.20120136] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2013] [Revised: 02/03/2013] [Accepted: 03/04/2013] [Indexed: 11/23/2022] Open
Abstract
Mucoadhesion can be defined as a state in which two components, of which one is of biological origin, are held together for extended periods of time by the help of interfacial forces. Among the various transmucosal routes, buccal mucosa has excellent accessibility and relatively immobile mucosa, hence suitable for administration of retentive dosage form. The objective of this paper is to review the works done so far in the field of mucoadhesive buccal drug delivery systems (MBDDS), with a clinical perspective. Starting with a brief introduction of the mucoadhesive drug delivery systems, oral mucosa, and the theories of mucoadhesion, this article then proceeds to cover the works done so far in the field of MBDDS, categorizing them on the basis of ailments they are meant to cure. Additionally, we focus on the various patents, recent advancements, and challenges as well as the future prospects for mucoadhesive buccal drug delivery systems.
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Affiliation(s)
- Ritu M Gilhotra
- Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Jaipur, Rajasthan 302025, India
| | - Mohd Ikram
- Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Jaipur, Rajasthan 302025, India
| | - Sunny Srivastava
- Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Jaipur, Rajasthan 302025, India
| | - Neeraj Gilhotra
- Faculty of Pharmacy, Maharshi Dayanand University, Rohtak, Haryana 124001, India
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Grant MM, Creese AJ, Barr G, Ling MR, Scott AE, Matthews JB, Griffiths HR, Cooper HJ, Chapple ILC. Proteomic analysis of a noninvasive human model of acute inflammation and its resolution: the twenty-one day gingivitis model. J Proteome Res 2010; 9:4732-44. [PMID: 20662485 PMCID: PMC2950674 DOI: 10.1021/pr100446f] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2010] [Indexed: 01/26/2023]
Abstract
The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC-MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins.
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Affiliation(s)
- Melissa M Grant
- Periodontal Research Group, School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, St. Chads Queensway, Birmingham, B4 6NN, United Kingdom.
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Drouganis A, Hirsch R. Low-dose aspirin therapy and periodontal attachment loss in ex- and non-smokers. J Clin Periodontol 2008. [DOI: 10.1111/j.1600-051x.2001.280106.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Perioli L, Pagano C, Mazzitelli S, Rossi C, Nastruzzi C. Rheological and functional characterization of new antiinflammatory delivery systems designed for buccal administration. Int J Pharm 2008; 356:19-28. [DOI: 10.1016/j.ijpharm.2007.12.027] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2007] [Revised: 12/14/2007] [Accepted: 12/18/2007] [Indexed: 11/29/2022]
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Yen CA, Damoulis PD, Stark PC, Hibberd PL, Singh M, Papas AS. The Effect of a Selective Cyclooxygenase-2 Inhibitor (Celecoxib) on Chronic Periodontitis. J Periodontol 2008; 79:104-13. [DOI: 10.1902/jop.2008.070271] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Aras H, Cağlayan F, Güncü GN, Berberoğlu A, Kilinç K. Effect of systemically administered naproxen sodium on clinical parameters and myeloperoxidase and elastase-like activity levels in gingival crevicular fluid. J Periodontol 2007; 78:868-73. [PMID: 17470020 DOI: 10.1902/jop.2007.060412] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND The present study was conducted to determine the possible effect of naproxen sodium on clinical status and the enzymatic profile of gingival crevicular fluid (GCF) when given as adjunct to periodontal treatment. METHODS A total of 34 subjects with chronic periodontitis were selected and divided into two groups to receive either naproxen sodium or placebo. At baseline, GCF samples were obtained and probing depths (PD), gingival index (GI), plaque index (PI), and gingival bleeding index (GBI) scores were recorded. In the non-steroidal anti-inflammatory drug (NSAID) group, patients were treated with a protocol consisting of baseline periodontal treatment (scaling, root planing) and naproxen sodium (275 mg) administration daily for 6 weeks. In the placebo group, patients received the same treatment except placebo was given instead of naproxen sodium. At the end of the experimental period, clinical recordings and GCF sampling were repeated. Myeloperoxidase (MPO) and elastase-like enzyme activity (ELA) levels were determined in GCF samples by a spectrophotometric method. GCF enzymatic content was calculated both as total enzyme activity and enzyme concentration. RESULTS All of the clinical parameters, except mean GBI, were significantly lower in the experimental group (P <0.05). At baseline and at the end of the experimental period, there were no significant differences between the NSAID and placebo groups regarding GCF MPO and ELA levels in either mode of data presentation (P <0.05). However, in the NSAID group, mean ELA concentration (P = 0.002) and mean total ELA (P = 0.003) presented significant decreases with treatment. Also, with treatment, a general reduction in MPO levels was seen; however, this difference was not significant. Although constant and stable correlations between GCF enzyme levels and clinical parameters could not be found, positive and strong correlations were observed between total enzyme activity and enzyme concentrations. CONCLUSION Based on the positive clinical effect and the ELA profile of GCF, it can be suggested that NSAIDs given as an adjunct to baseline periodontal treatment could be beneficial in the outcome of treatment.
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Perioli L, Ambrogi V, Giovagnoli S, Ricci M, Blasi P, Rossi C. Mucoadhesive bilayered tablets for buccal sustained release of flurbiprofen. AAPS PharmSciTech 2007; 8:E54. [PMID: 17915804 PMCID: PMC2750373 DOI: 10.1208/pt0803054] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2006] [Revised: 01/23/2007] [Accepted: 11/27/2006] [Indexed: 11/30/2022] Open
Abstract
The aim of this work was the design of sustained-release mucoadhesive bilayered tablets, using mixtures of mucoadhesive polymers and an inorganic matrix (hydrotalcite), for the topical administration of flurbiprofen in the oral cavity. The first layer, responsible for the tablet retention on the mucosa, was prepared by compression of a cellulose derivative and polyacrylic derivative blend. The second layer, responsible for buccal drug delivery, was obtained by compression of a mixture of the same (first layer) mucoadhesive polymers and hydrotalcite containing flurbiprofen. Nonmedicated tablets were evaluated in terms of swelling, mucosal adhesion, and organoleptic characteristics; in vitro and in vivo release studies of flurbiprofen-loaded tablets were performed as well. The best results were obtained from the tablets containing 20 mg of flurbiprofen, which allowed a good anti-inflammatory sustained release in the buccal cavity for 12 hours, ensuring efficacious salivary concentrations, and led to no irritation. This mucoadhesive formulation offers many advantages over buccal lozenges because it allows for reduction in daily administrations and daily drug dosage and is suitable for the treatment of irritation, pain, and discomfort associated with gingivitis, sore throats, laryngopharyngitis, cold, and periodontal surgery. Moreover, it adheres well to the gum and is simple to apply, which means that patient compliance is improved.
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Affiliation(s)
- Luana Perioli
- Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia, Via del Liceo, 1 Perugia, 06123, Italy.
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Kurtiş B, Tüter G, Serdar M, Pinar S, Demirel I, Toyman U. Gingival crevicular fluid prostaglandin E(2) and thiobarbituric acid reactive substance levels in smokers and non-smokers with chronic periodontitis following phase I periodontal therapy and adjunctive use of flurbiprofen. J Periodontol 2007; 78:104-11. [PMID: 17199546 DOI: 10.1902/jop.2007.060217] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND It has been established that smoking is an important risk factor for the initiation and progression of chronic periodontitis (CP). This study investigates the effects of phase I periodontal therapy and adjunctive flurbiprofen administration on prostaglandin E(2) (PGE(2)) and thiobarbituric acid reactive substance (TBARS) levels in gingival crevicular fluid (GCF) samples from smoker and non-smoker patients with CP. METHODS Twenty-one non-smoker and 21 smoker patients with CP were divided into four groups according to treatment modalities. Group 1 (non-smokers with CP) and group 3 (smokers with CP) patients received daily 100-mg flurbiprofen tablets in a 2 x 1 regimen for 10 days together with scaling and root planing (SRP). Patients in group 2 (non-smokers with CP) and group 4 (smokers with CP) received placebo tablets in a 2 x 1 regimen for 10 days together with SRP. Plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL) measurements were recorded and GCF samples were collected at baseline and on day 10 of drug intake from each sampling area by a single examiner who was unaware of the treatment modality. Assays for GCF PGE(2) and TBARS were carried out by an enzyme-linked immunosorbent assay and fluorometric method, respectively. RESULTS All groups showed statistically significant reductions in PI and GI scores following the phase I periodontal treatment on day 10 (P <0.05), but no statistical differences were observed in PD and CAL scores after the therapy. In groups 1 and 2, the reduction of GCF PGE(2) and TBARS levels were not significant after the therapy compared to baseline levels. In group 3, GCF PGE(2) and TBARS levels exhibited a statistically significant decrease (P <0.05) after the therapy. Group 4 showed significant reductions (P <0.05) in GCF PGE(2) levels after the therapy. No statistically significant reductions were observed in group 4 with regard to GCF TBARS levels. When groups 1 and 3 were compared according to GCF TBARS levels after the therapy, a more statistically significant reduction was observed in group 3 (P = 0.001). CONCLUSION These results suggest that additional flurbiprofen administration may have more inhibitory effects on GCF levels of PGE(2) and TBARS in the groups of smokers compared to non-smokers with CP.
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Affiliation(s)
- Bülent Kurtiş
- Department of Periodontology, Faculty of Dentistry, Gazi University, Ankara, Turkey.
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Müller HP, Barrieshi-Nusair KM, Könönen E, Yang M. Effect of triclosan/copolymer-containing toothpaste on the association between plaque and gingival bleeding: a randomized controlled clinical trial. J Clin Periodontol 2006; 33:811-8. [PMID: 16965523 DOI: 10.1111/j.1600-051x.2006.00993.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
AIM To study longitudinal associations between plaque and gingival bleeding and multilevel variance/covariance structures after introducing triclosan-containing toothpaste. MATERIAL AND METHODS A 10-week, randomized, two-arm, double-masked, controlled clinical trial was conducted in 34 healthy, non-smoking females with plaque-induced gingivitis. Clinical periodontal examinations were repeated every other week. At week 4, test toothpaste containing 0.24% sodium monofluorophosphate, 0.3% triclosan, and 2% polyvinyl-methyl ether maleic acid; or control toothpaste containing 0.76% sodium monofluorophosphate and 0.1% sodium fluoride, were randomly distributed. RESULTS Multivariate multilevel models indicated that, after introducing experimental toothpastes, subject random error was reduced from 0.6 to below 0.2. The odds ratio (OR) of bleeding on probing (BOP) was about 30% less in the test than in the control group (p<0.01). At the end of the experiment, ORs for BOP and plaque index scores 1-3 (reference 0) were 2.1-2.4 in the control group, but 1.1-1.9 in the test group (p<0.05). No effects on plaque levels and calculus were observed. CONCLUSIONS Multivariate multilevel modelling allows the study of fixed and random effects of experimental toothpastes on gingival inflammation in small sample. Triclosan appears to attenuate the causal association between supragingival plaque and gingival bleeding in gingivitis.
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Affiliation(s)
- H P Müller
- Faculty of Dentistry, Kuwait University, Kuwait.
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Abstract
OBJECTIVE To review the biological mechanisms and clinical utility of therapeutic modulation of the host response in the management of periodontal diseases. MATERIAL AND METHODS A search of MEDLINE-PubMed was performed up to and including December 2004. The search was limited to in vitro, experimental animal and clinical studies published in English. The selection criteria included all levels of available evidence: systematic reviews, randomised-controlled clinical trials, controlled clinical trials, prospective and retrospective cohort studies and case reports of human and experimental animal studies. RESULTS Six targets for non-microbial chemotherapeutic intervention were identified. Clinical trials have demonstrated the ability of non-steroidal anti-inflammatory drugs to slow periodontal disease progression. However, recently reported serious adverse effects preclude the use of cyclooxygenase-2 inhibitors as an adjunct to periodontal therapy. Adjunctive use of subantimicrobial dose doxycycline to non-surgical periodontal therapy is beneficial in the management of chronic periodontitis over 12 months. Controversial data exist on the effects of bisphosphonate administration as an adjunct to periodontal therapy. Evidence on modulation of other host mediators including lipoxins, cytokines and nitric oxide synthase is limited to animal research. CONCLUSION After validation in long-term clinical trials, adjunctive host modulation therapy may prove advantageous in the management of periodontal diseases.
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Affiliation(s)
- Giovanni E Salvi
- University of Berne, School of Dental Medicine, Berne, Switzerland.
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Rosin M, Kähler ST, Hessler M, Schwahn C, Kuhr A, Kocher T. The effect of a dexibuprofen mouth rinse on experimental gingivitis in humans. J Clin Periodontol 2005; 32:617-21. [PMID: 15882220 DOI: 10.1111/j.1600-051x.2005.00721.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVES The pharmacodynamic properties of ibuprofen are related nearly exclusively to the S(+)enantiomer (dexibuprofen). This study investigated the effect of a 1.5% dexibuprofen mouth rinse in an experimentally induced gingivitis. MATERIALS AND METHODS The trial was a randomized, double-blinded, placebo-controlled, two-period and two-sequence parallel group cross-over study in 24 healthy volunteers aged 21-30 years (16 males, eight females). Customized guards were worn during tooth brushing to prevent any plaque removal from the experimental area (first and second pre-molars and molars in one upper quadrant). After 22 days of plaque accumulation, the mouth rinses (1.5% dexibuprofen and placebo) were administered under supervision three times daily (rinsing for 1 min. with 15 ml) for 8 days. The wash-out time between the two study periods was 14 days. Parameters evaluated at days 0, 7, 14, 22, and 30 were the Löe & Silness gingival index (GI) and the Quigley & Hein plaque index (QHI). Data were tested for treatment, period, and carry-over effects (parametric cross-over analysis). RESULTS There was no statistically significant difference (p=0.240) in GI between placebo and dexibuprofen. However, the decrease in QHI was significantly greater (p=0.019) with dexibuprofen as compared with the placebo. CONCLUSION In the present study, a 1.5% dexibuprofen mouth rinse had no effect on gingivitis whereas an anti-plaque effect was demonstrated.
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Affiliation(s)
- M Rosin
- Department of Periodontology, Eastman Dental Institute, University College London, London, UK.
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Abstract
The two most prevalent and most investigated periodontal diseases are dental plaque-induced gingivitis and chronic periodontitis. The last 10 to 15 years have seen the emergence of several important new findings and concepts regarding the etiopathogenesis of periodontal diseases. These findings include the recognition of dental bacterial plaque as a biofilm, identification and characterization of genetic defects that predispose individuals to periodontitis, host-defense mechanisms implicated in periodontal tissue destruction, and the interaction of risk factors with host defenses and bacterial plaque. This article reviews current aspects of the etiology and pathogenesis of periodontal diseases.
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Affiliation(s)
- Dimitris N Tatakis
- Section of Periodontology, College of Dentistry, The Ohio State University, Columbus, OH 43218-2357, USA.
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Sekino S, Ramberg P, Lindhe J. The effect of systemic administration of ibuprofen in the experimental gingivitis model. J Clin Periodontol 2005; 32:182-7. [PMID: 15691349 DOI: 10.1111/j.1600-051x.2005.00671.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Studies in humans have indicated that systemically administered flurbiprofen and ibuprofen may reduce gingivitis. De novo plaque formation is enhanced at tooth surfaces adjacent to inflamed gingivae. OBJECTIVE The aim of the present clinical trial was to evaluate the effect of systemic administration of ibuprofen on gingivitis and plaque build-up. MATERIAL AND METHODS Eleven subjects were recruited for the study and were given oral hygiene instruction, scaling and professional mechanical tooth cleaning (PTC). At the end of a preparatory period (Day 0), the participants were told to abstain from all mechanical plaque control measures during a 2-week experimental period but to rinse with an assigned mouth rinse (positive control: 0.1% chlorhexidine digluconate; negative control: saline) or administer ibuprofen (tablets of 200 mg twice daily). Mouth rinsing was performed twice a day (after breakfast and in the evening), for 60 s with 10 ml. Re-examination was performed after 14 days of experiment. After a 2-week "wash-out" period, the participants received a new PTC and a second 14-day experimental period was initiated. The experimental and "wash-out" periods were repeated until all volunteers had been involved in all three regimens. Dental plaque was scored using the Quigley & Hein Plaque Index system and gingivitis according to the Gingival Index (GI) system. Supragingival plaque was collected and prepared for dark-field microscopy. One hundred bacterial cells were counted and classified into six different groups: coccoid cells, straight rods, filaments, fusiforms, spirochetes and motile rods. Gingival crevicular fluid (GCF) was collected from the same sites that were sampled for plaque. The volume of GCF collected in each strip was measured and analysed regarding content of lactoferrin and albumin. RESULTS During the period when the panelists rinsed with saline they accumulated large amounts of plaque and developed marked signs of gingivitis. When they rinsed with chlorhexidine digluconate, small amounts of plaque formed and few sites received GI score > or =2. After the 2 weeks of ibuprofen administration, the panelists presented with significantly fewer sites that scored GI > or =2 but had formed similar amounts of plaque as during the negative control period. CONCLUSION It is suggested that ibuprofen administered via the systemic route has an effect on gingivitis but not on de novo plaque formation.
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Affiliation(s)
- Satoshi Sekino
- Department of Periodontology, Faculty of Odontology, The Sahlgrenska Academy at Göteborg University, SE-405 30 Göteborg, Sweden
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Gurgel BCDV, Duarte PM, Nociti FH, Sallum EA, Casati MZ, Sallum AW, de Toledo S. Impact of an Anti-Inflammatory Therapy and Its Withdrawal on the Progression of Experimental Periodontitis in Rats. J Periodontol 2004; 75:1613-8. [PMID: 15732862 DOI: 10.1902/jop.2004.75.12.1613] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Anti-inflammatory agents have been reported as a bone loss mediator in periodontitis. This study aimed to investigate in rats the impact of a selective cyclooxygenase-2 inhibitor (meloxicam) on bone loss in ligature-induced periodontitis and its post-treatment effect after administration withdrawal. METHODS Seventy-five adult male Wistar rats were included. After anesthesia, a mandibular first molar was randomly assigned to receive the cotton ligature in the sulcular position, while the contralateral tooth was left unligated. The animals were randomly assigned to one of the following five treatment groups (15 animals each), including daily subcutaneous injections: 1) saline solution for 15 days; 2) saline solution for 45 days; 3) 3 mg/kg of meloxicam for 15 days; 4) 3 mg/kg of meloxicam for 45 days; or 5) 3 mg/kg of meloxicam for 15 days followed by saline solution for 30 days. The animals were sacrificed and the specimens routinely processed. The volume of bone loss was histometrically measured and statistical analysis performed. RESULTS Intergroup comparisons demonstrated that the drug may significantly reduce periodontitis-related bone loss (group 3: 5.83 +/- 2.04); however, this effect is less evident when the drug is administered in a short period (group 4: 3.59 +/- 1.57). Moreover, after drug withdrawal, no residual effect was observed (6.86 +/- 3.59, 6.09 +/- 2.66, groups 2 and 5, respectively) (P > 0.05). CONCLUSIONS Within the limits of the present study, it can be concluded that selective cyclooxygenase-2 inhibitors may reduce bone loss associated with experimental periodontitis and that no remaining effect can be expected after its withdrawal.
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Tatakis DN, Trombelli L. Modulation of clinical expression of plaque-induced gingivitis. I. Background review and rationale. J Clin Periodontol 2004; 31:229-38. [PMID: 15016250 DOI: 10.1111/j.1600-051x.2004.00477.x] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVES The purpose of this article is to provide the necessary background and rationale for the accompanying studies, which are ultimately aimed at identifying genetic and environmental factors determining gingivitis susceptibility. MATERIALS AND METHODS The literature on factors reported to modify the clinical expression of gingivitis, i.e., factors that determine individual variability in gingival inflammatory response to plaque, is presented. RESULTS Clinical evidence suggests that the gingival inflammatory response to plaque accumulation may differ substantially among individuals. However, most of the available studies are of small scale and not purposely designed to address the issue. Systemic factors implicated in modulation of the clinical expression of gingivitis include metabolic, genetic, environmental and other factors. The significance of such factors in designing and conducting a large-scale experimental gingivitis trial and means to account for them are discussed. CONCLUSION Although several factors have been implicated, genetic or environmental factors underlying differences in gingivitis expression are not fully elucidated. The accompanying studies aim to identify and characterize, among participants in a specifically designed large-scale experimental gingivitis trial, subjects that differ significantly in their gingival inflammatory response to plaque. This is the first step in an effort to determine genetic or environmental factors underlying such differences.
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Affiliation(s)
- Dimitris N Tatakis
- Section of Periodontology, College of Dentistry, The Ohio State University, Columbus, OH 43218-2357, USA.
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Reddy MS, Geurs NC, Gunsolley JC. Periodontal host modulation with antiproteinase, anti-inflammatory, and bone-sparing agents. A systematic review. ACTA ACUST UNITED AC 2004; 8:12-37. [PMID: 14971246 DOI: 10.1902/annals.2003.8.1.12] [Citation(s) in RCA: 151] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND The use of modulating agents, including inhibition of matrix metalloproteinases (MMPs) with antiproteinases, blocking production of proinflammatory cytokines and prostaglandins with anti-inflammatory drugs, and inhibiting activation of osteoclasts with bone-sparing agents, has been postulated to be of therapeutic value as an adjunctive therapy to the management of chronic periodontitis. RATIONALE The objective of this systematic review of the literature was to assess the adjunctive efficacy of antiproteinase, anti-inflammatory, and bone-sparing host-modulating agents in the treatment of gingivitis, aggressive periodontitis, and chronic periodontitis. FOCUSED QUESTIONS: 1. In patients with periodontal diseases, what is the effect of host-modulation agents, alone or combined with conventional therapy, compared to conventional therapy alone as assessed by clinical, radiographic, adverse, and patient-centered outcomes? 2. In patients with dental implants, what is the effect of host-modulation agents on implant success assessed by clinical, radiographic, adverse, and patient-centered outcomes? SEARCH PROTOCOL MEDLINE, Embase, and the Cochrane Library databases were searched without language restrictions through April 1, 2002 for studies that used tetracycline (TET)-related matrix metalloproteinase (MMP) inhibitors, or non-steroidal anti-inflammatory drugs (NSAIDs) and bisphosphonate anti-osteolytic agents. The investigation also included hand searching of journals and contacting authors and industry experts. SELECTION CRITERIA INCLUSION CRITERIA Only human studies (randomized controlled clinical trials, cohort studies, case-control studies, cross-sectional studies, and case series) were selected. Studies were on subjects with gingivitis, aggressive or chronic periodontitis, or dental implants. Interventions included TET-related MMP inhibitors, NSAIDs, or bisphosphonate anti-osteolytic agents. EXCLUSION CRITERIA Studies that used MMP tissue inhibitors as diagnostic or prognostic indicators of periodontal disease or that evaluated short-term systemic antibodies or locally delivered levels of drugs with antiproteinase activity were excluded. DATA COLLECTION AND ANALYSIS The primary outcomes for assessment were changes in bone or clinical attachment levels (CAL); secondary outcomes included clinical measures of plaque, gingival inflammation, probing depth (PD), and mobility. Summary data appropriate for meta-analysis were pooled using a weighted average and analyzed using a standardized difference; the results were checked with both fixed-effects and random-effects models. MAIN RESULTS 1. A meta-analysis done on the studies reporting changes in CAL and PD following administration of sub-antimicrobial doses of doxycycline (SDD) in conjunction with scaling and root planing (SRP) in patients with periodontitis showed a statistically significant beneficial adjunctive effect. 2. There were insufficient data to provide meta-analyses on periodontal patients treated with other host-modulating agents; descriptive tables are included. 3. NSAIDS show promise in their ability to slow periodontal disease. 4. Preliminary data on bisphosphonate agents indicate there is a potential role for these agents in periodontitis management. 5. There are a very limited number of studies on host-modulating agents and dental implants and no analyses were possible. 6. Because the treatment methodologies and clinical variables differed considerably among the studies, it is difficult to summarize the information and identify a reliable total patient population. REVIEWERS' CONCLUSIONS 1. Large multi-center trials are needed to evaluate the role of host-modulating agents in the treatment of periodontitis. 2. NSAIDS and bisphosphonate drugs may have a potential adjunctive role in periodontal therapy. 3. The adjunctive use of SDD with SRP is statistically more effective than SRP alone in reducing PD and in achieving CAL gain.
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Affiliation(s)
- Michael S Reddy
- University of Alabama, Birmingham School of Dentistry, Department of Periodontology, Birmingham, Alabama, USA
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Sakaki H, Matsumiya T, Kusumi A, Imaizumi T, Satoh H, Yoshida H, Satoh K, Kimura H. Interleukin-1beta induces matrix metalloproteinase-1 expression in cultured human gingival fibroblasts: role of cyclooxygenase-2 and prostaglandin E2. Oral Dis 2004; 10:87-93. [PMID: 14996278 DOI: 10.1046/j.1354-523x.2003.00982.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE Matrix metalloproteinases (MMPs) degrade extracellular matrices and are responsible for excessive connective tissue breakdown in inflammatory disorders. We investigated the mechanism of MMP-1 expression in human gingival fibroblasts in response to the stimulation with interleukin-1beta (IL-1beta), and the role of inducible-type cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in the regulation of MMP-1 expression. MATERIALS AND METHODS We stimulated cultured human gingival fibroblasts with r(h)IL-1beta, and examined the expression of MMP-1 mRNA and protein by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The effect of indomethacin, dexamethasone, or cycloheximide (CHX) on the IL-1beta-induced expression of MMP-1 was examined. The expression of MMP-1 in gingival fibroblasts stimulated with PGE2 was also examined. RESULTS IL-1beta stimulated the expressions of mRNA and protein for MMP-1, in cultured fibroblasts, in time- and concentration-dependent manners. Pretreatment of the cells with indomethacin or dexamethasone inhibited the IL-1beta-induced MMP-1 expression. CHX, a protein synthesis inhibitor, also suppressed the MMP-1 expression. IL-1beta also induced COX-2 expression in gingival fibroblasts, and PGE2, a major COX-2 product, was found to enhance MMP-1 expression. CONCLUSION The IL-1beta-induced MMP-1 expression in gingival fibroblasts may be mediated, at least in part, by COX-2 and its product PGE2.
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Affiliation(s)
- H Sakaki
- Department of Dentistry and Oral Surgery, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan.
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Champagne CME, Buchanan W, Reddy MS, Preisser JS, Beck JD, Offenbacher S. Potential for gingival crevice fluid measures as predictors of risk for periodontal diseases. Periodontol 2000 2003; 31:167-80. [PMID: 12657001 DOI: 10.1034/j.1600-0757.2003.03110.x] [Citation(s) in RCA: 136] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Vardar S, Baylas H, Huseyinov A. Effects of selective cyclooxygenase-2 inhibition on gingival tissue levels of prostaglandin E2 and prostaglandin F2alpha and clinical parameters of chronic periodontitis. J Periodontol 2003; 74:57-63. [PMID: 12593597 DOI: 10.1902/jop.2003.74.1.57] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND The purpose of the present study was to evaluate the effect of a relatively selective cyclooxygenase (COX)-2 inhibitor (nimesulide) and non-selective COX-1/COX-2 inhibitor (naproxen) used as an adjunct to non-surgical (scaling and root planing [SRP]) periodontal therapy in chronic periodontitis patients on the gingival tissue (GT) levels of prostaglandin (PG)E2 and PGF2alpha. METHODS Thirty patients with chronic periodontitis were divided into 3 groups of 10 each. One group received 100 mg of nimesulide; one received 275 mg of naproxen sodium; and the third group received placebo tablets in a 2 x 1 regimen for 10 days as an adjunct to SRP. GT samples were obtained before drug intake and on day 10. Plaque index (PI) and papillary bleeding index (PBI) scores were recorded at baseline, day 10, and at 3 months; probing depth (PD) and clinical attachment level (CAL) were recorded at baseline and at 3 months. The levels of PGE2 were detected using an enzyme immunoassay (EIA), and the levels of PGF2alpha were analyzed by radioimmunoassay (RIA). Differences among and within the groups were assessed using non-parametric statistical analysis. Ten periodontally healthy individuals served as controls. RESULTS All 3 groups showed statistically significant reductions in PBI and PI on day 10 and at 3 months (P < 0.02), and in PD and CAL at 3 months (P < 0.02, P < 0.05, respectively). In the naproxen group, GT PGE2 levels exhibited a significant decrease (P < 0.05). However, the decrease of GT PGE2 levels in the nimesulide group was insignificant (P > 0.05), while a significant increase was observed in the placebo group (P < 0.05) on day 10. Both the nimesulide and naproxen groups showed a significant decrease (P<0.05) in PGF2alpha level, while the placebo group showed a significant increase (P<0.05). CONCLUSIONS Nimesulides, relatively selective COX-2 inhibitors, may have additional inhibitory effects on GT PGF2alpha levels in the first week following non-surgical periodontal treatment. However, nimesulide has an insignificant effect on reducing PGE2 levels in gingival tissue. The determination of GT levels of COX-1 and COX-2 enzymes as well as PGE2 and PGF2alpha in long-term studies may provide further support for the adjunctive use of selective COX-2 inhibitors in treatment of chronic periodontitis.
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Affiliation(s)
- Saynur Vardar
- Department of Periodontology, School of Dentistry, Ege University, Izmir, Turkey.
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Schrodi J, Recio L, Fiorellini J, Howell H, Goodson M, Karimbux N. The effect of aspirin on the periodontal parameter bleeding on probing. J Periodontol 2002; 73:871-6. [PMID: 12211496 DOI: 10.1902/jop.2002.73.8.871] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND The absence or presence of bleeding on probing (BOP) is a sign of periodontal health or disease, but the presence of BOP is not an accurate predictor of disease progression. Aspirin is increasingly used in the prevention of cerebrovascular and cardiovascular diseases and is a non-disease factor that may modify bleeding indices given its antithrombolytic activity. The purpose of this double-blind placebo-controlled randomized clinical trial was to study the effect of short-term daily aspirin ingestion on the clinical parameter BOP. METHODS A total of 46 periodontally healthy subjects were included in this study: 16 received placebo, 15 low-dose aspirin (81 mg), and 15 regular dose (325 mg) aspirin. Clinical parameters assessed included plaque index, periodontal probing depth, and BOP using an automated pressure-sensitive probe. Measurements were recorded before and after 7-day exposure to placebo and aspirin regimens. RESULTS A statistically significant difference in BOP was found in patients with > or = 20% of bleeding sites during the visit prior to placebo or aspirin exposure (n = 11). The group treated with 325 mg aspirin exhibited a moderate yet statistically significant increase in BOP (12.4%) compared to the placebo group (there was no significant difference between the 81 mg aspirin group and placebo). The tendency to bleed was not statistically significant in the group which exhibited <20% (n = 35) of bleeding sites during the visit prior to exposure. CONCLUSION Aspirin intake of 325 mg daily for 7 days moderately increased the appearance of bleeding on probing in a population that had > or = 20% BOP sites.
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Affiliation(s)
- Janet Schrodi
- Departments of Pediatric Dentistry and Orthodontics, UCLA School of Dentistry, Los Angeles, CA, USA
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Abstract
This paper was prepared by the Research, Science, and Therapy Committee of the American Academy of Periodontology to provide the dental profession an overview of current and potential methods to modulate the host response in the treatment of periodontal diseases. Specifically, it discusses components of periodontal disease pathogenesis (i.e., immune and inflammatory responses, excessive production of matrix metalloproteinases and arachidonic acid metabolites, and regulation of bone metabolism) and their modulation.
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Dionne RA, Berthold CW. Therapeutic uses of non-steroidal anti-inflammatory drugs in dentistry. CRITICAL REVIEWS IN ORAL BIOLOGY AND MEDICINE : AN OFFICIAL PUBLICATION OF THE AMERICAN ASSOCIATION OF ORAL BIOLOGISTS 2002; 12:315-30. [PMID: 11603504 DOI: 10.1177/10454411010120040301] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used classes of drugs for the management of acute and chronic pain in dentistry. Their therapeutic efficacy and toxicity are well-documented and provide evidence that NSAIDs generally provide an acceptable therapeutic ratio of pain relief with fewer adverse effects than the opioid-mild analgesic combination drugs that they have largely replaced for most dental applications. The great many studies done with the oral surgery model of acute pain indicate that a single dose of an NSAID is more effective than combinations of aspirin or acetaminophen plus an opioid, with fewer side-effects, thus making it preferable for ambulatory patients. The combination of an NSAID with an opioid generally results in marginal analgesic activity but with an increased incidence of side-effects, which limits its use to patients in whom the NSAID alone results in inadequate analgesia. The selective COX-2 inhibitors hold promise for clinical efficacy with less toxicity from chronic administration and may prove advantageous for the relief of chronic orofacial pain. The use of repeated doses of NSAIDs for chronic orofacial pain should be re-evaluated in light of a lack of documented efficacy and the potential for serious gastrointestinal and renal toxicity with repeated dosing.
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Affiliation(s)
- R A Dionne
- Pain & Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892-1258, USA.
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Clinical effect of ibuprofen as an adjunct to non-surgical periodontal disease treatment. ZBORNIK MATICE SRPSKE ZA PRIRODNE NAUKE 2002. [DOI: 10.2298/zmspn0201077d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Twenty five patients with progresive periodontal disease entered this study in order to examine clinical effects of a non-steroidal anti-inflammatory drug - ibuprofen, used as an adjunct to non-surgical periodontal treatment. After scaling and root planning, patients were randomly assigned to either receive orally 200 mg of ibuprofen per day for one month (group A), or not receive the drug (group B). The obtained results show that the mechanical periodontal treatment brought to resolution the gingival inflammation with both group of patients. Although the mean values of the used indices were lower in group A than in group B, those differences were neither statistically nor clinically significant. We may conclude that systemic ibuprofen had no significant effect on plaque, gingival or bleeding index scores.
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Drouganis A, Hirsch R. Low-dose aspirin therapy and periodontal attachment loss in ex- and non-smokers. J Clin Periodontol 2001; 28:38-45. [PMID: 11142665 DOI: 10.1034/j.1600-051x.2001.280106.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND, AIMS This study investigated the periodontal status of non-smokers and ex-smokers in relation to their intake of low-dose aspirin. METHODS A self-selected sample of 392 males aged 50 years and over was recruited from the general population. Subjects were included in the study if they had a minimum of 6 or more natural teeth, took aspirin (300 mg or less per day) for at least 2 years and were either ex- or non-smokers. Controls were subjects who did not take aspirin regularly. A questionnaire was used to record demographic data, medical and dental histories. Individuals who had diabetes or other systemic diseases were excluded from the study. Periodontal attachment loss (PAL) was calculated by adding measurements of gingival recession and periodontal pocket depth made by a single examiner at 6 sites around each tooth using non-pressure sensitive periodontal probes. Plaque and gingival bleeding indices were also scored. Subjects were divided into 4 groups: aspirin non-smokers, aspirin ex-smokers, no aspirin non-smokers and no aspirin ex-smokers. Data were analysed using two-way ANOVA with age as the covariate. Severity and extent of mean PAL and the cumulative distribution of the mean of the most severe sites (MSS) of PAL were analysed. RESULTS Controlling for age, mean PAL in aspirin takers was significantly less 2.6+/-0.08 (se) mm than non-aspirin takers 2.9+/-0.06 (se) mm; this association was independent of smoking history. Ex-smokers had significantly more mean PAL 3.9+/-0.07 (se) mm than non-smokers 2.6+/-0.08 (se) mm, irrespective of aspirin status. When MSS-PAL was analysed, these differences became more pronounced; MSS-PAL in aspirin takers was significantly less 3.9+/-0.1 (se) mm than non-aspirin takers 4.2+/-0.08 (se) mm. Ex-smokers had significantly more MSS-PAL 4.3+/-0.08 (se) mm than non-smokers 3.8+/-0.08 (se) mm. Aspirin apparently had a protective association on PAL and it is hypothesised that low-dose aspirin may have reduced the rate of attachment loss. CONCLUSIONS This hypothesis needs to be confirmed by a prospective study. The results of this study suggest that individuals aged over 50 years, particularly ex-smokers, may benefit by taking low-doses of aspirin daily to reduce their risk of periodontal attachment loss.
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Affiliation(s)
- A Drouganis
- Dental School, The University of Adelaide, Australia
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Noguchi K, Iwasaki K, Ishikawa I. Prostaglandin F2 alpha upregulates intercellular adhesion molecule-1 expression in human gingival fibroblasts. J Periodontal Res 1999; 34:277-81. [PMID: 10567951 DOI: 10.1111/j.1600-0765.1999.tb02254.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Prostaglandin F2 alpha (PGF2 alpha) is a bioactive lipid mediator, which has been suggested to be involved in the pathogenesis of periodontal disease. However, the roles of PGF2 alpha in the disease are not well understood. In the present study, we investigated the effect of PGF2 alpha on intercellular adhesion molecule-1 (ICAM-1) expression in human gingival fibroblasts (HGF) and the effect of PGF2 alpha on ICAM-1 expression elicited by proinflammatory cytokines, interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF alpha) in the cells. PGF2 alpha-stimulated HGF expressed ICAM-1 expression in a time- and dose-dependent manner. IFN-gamma-elicited ICAM-1 expression was synergistically increased by PGF2 alpha, whereas TNF alpha-induced ICAM-1 expression was slightly inhibited by PGF2 alpha. Fluprostenol, a selective FP receptor agonist, could mimic PGF2 alpha-induced effect on ICAM-1 expression. Furthermore, signal transduction for the regulation of ICAM-1 by PGF2 alpha was investigated using N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7), a calcium calmodulin antagonist, and 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C (PKC). W-7 and H-7, remarkably, suppressed PGF2 alpha-induced ICAM-1 expression and synergistic increase of ICAM-1 expression by combination of PGF2 alpha and IFN-gamma, while IFN-gamma-elicited ICAM-1 expression was only partially inhibited by W-7 and H-7. From these data, we suggest that PGF2 alpha upregulates ICAM-1 expression in HGF and synergistically enhances IFN-gamma-induced ICAM-1 expression through FP receptor by calcium calmodulin-dependent and PKC-dependent pathways. PGF2 alpha may be involved in the pathology of periodontal disease by upregulating ICAM-1 expression in HGF.
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Affiliation(s)
- K Noguchi
- Department of Periodontology, Faculty of Dentistry, Tokyo Medical & Dental University, Japan.
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Jones DS, Irwin CR, Woolfson AD, Djokic J, Adams V. Physicochemical characterization and preliminary in vivo efficacy of bioadhesive, semisolid formulations containing flurbiprofen for the treatment of gingivitis. J Pharm Sci 1999; 88:592-8. [PMID: 10350494 DOI: 10.1021/js9803095] [Citation(s) in RCA: 68] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
In this study, the physicochemical properties and preliminary in vivo clinical performance of formulations containing hydroxyethylcellulose (HEC; 3, 5, 10% w/w), poly(vinylpyrrolidone) (PVP; 3, 5% w/w), polycarbophil (PC; 1, 3, 5% w/w), and flurbiprofen (5% w/w) were examined. Flurbiprofen release into PBS pH 7.4 was performed at 37 degrees C. The mechanical properties (hardness, compressibility, adhesiveness, initial stress) and syringeability of formulations were determined using a texture analyzer in texture profile analysis (TPA) and compression modes, respectively. In general, the time required for release of 10 and 30% of the original mass of flurbiprofen (t10%, t30%) increased as the concentration of each polymeric component increased. However, in the presence of either 5 or 10% HEC and 5% PC, increased PVP concentration decreased both t10%, t30% due to excessive swelling (and disintegration) of these formulations. Increased concentrations of HEC, PVP, and PC significantly increased formulation hardness, compressibility, work of syringe expression, and initial stress due to the effects of these polymers on formulation viscoelasticity. Similarly, increased concentrations of PC (primarily), HEC, and PVP increased formulation adhesiveness due to the known bioadhesive properties of these polymers. Clinical efficacies of formulations containing 3% HEC, 3% PVP, 3% PC, and either 0% (control) or 5% (test) flurbiprofen, selected to offer optimal drug release and mechanical properties, were evaluated and clinically compared in an experimental gingivitis model. The test (flurbiprofen-containing) formulation significantly reduced gingival inflammation, as evaluated using the gingival index, and the gingival crevicular fluid volume, whereas, these clinical parameters were generally increased in volunteers who had received the control formulation. There were no observed differences in the plaque indices of the two subject groups, confirming that the observed differences in gingival inflammation could not be accredited to differences in plaque accumulation. This study has shown both the applicability of the in vitro methods used, particularly TPA, for the rational selection of formulations for clinical evaluation and, additionally, the clinical benefits of the topical application of a bioadhesive semisolid flurbiprofen-containing formulation for the treatment of experimental gingivitis.
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Affiliation(s)
- D S Jones
- The Pharmaceutical Sciences Group, School of Pharmacy, and Division of Restorative Dentistry (Periodontics), The Queen's University of Belfast, Medical Biology Centre, 97, Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom.
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Breen HJ, Rogers PA, Slaney RE, Gillett IR, Johnson NW. Option-4 algorithm for third generation disc probe: agreement of selected site-specific relative attachment level measurements and detection of longitudinal site-specific attachment level change. J Periodontol 1999; 70:159-70. [PMID: 10102553 DOI: 10.1902/jop.1999.70.2.159] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Longitudinal site-specific attachment level change (SSAC), identified from serial relative attachment level measurements (RAL), is the principal indicator of progression/regression of periodontal diseases. Many variables confound RAL reproducibility and affect measurement error. The Option-4 algorithm was designed to reduce measurement error and improve accuracy and sensitivity of SSAC detection. The study aimed to evaluate the performance of the Option-4 algorithm. METHODS A precalibrated clinician recorded full mouth RAL with a third generation disc probe on 4 occasions over 6 months in 16 subjects (mean age 48.1 years) with moderately advanced chronic adult periodontitis (2,312 sites). Option-4 allowed up to 4 RAL recordings per site per visit until 2 values had differences < or =1.0 mm and their mean was < or =1.0 mm from the previous visit mean: the clinician made the selection if these criteria were unfulfilled. RESULTS Within-visit agreement < or =1.0 mm was > or =99.6%: all within-visit correlation coefficients = 0.98 (P<0.001). At each visit, mean difference in Option-4 values was < 0.05 mm, mean absolute difference (ignoring direction) was < or =.34 mm. Mean site-specific variances ranged from 0.092 mm2 to 0.097 mm2 across all visits. Subject thresholds for site-specific attachment level change (from estimated 95% confidence limits of visit 1 data) ranged from 0.52 mm to 0.67 mm. Linear SSAC (by linear regression) and between-visit patterns of SSAC were investigated. SSAC was detected in 100% subjects and at 51.0% measured sites. Linear SSAC (R2 > or =0.90: P < or =0.05) occurred at 105 sites (4.5%): 32 sites (1.4%) deteriorated, 73 sites (3.1%) improved. Between-visit SSAC occurred at 1,074 sites (46.5%): 391 sites (16.9%) deteriorated, 295 sites (12.8%) improved, and 388 sites (16.8%) showed exacerbation/remission patterns. CONCLUSIONS The Option-4 algorithm produced high RAL agreement. Site-specific attachment level change was detected in both directions in 100% subjects and at 51.0% measured sites.
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Affiliation(s)
- H J Breen
- Clinical Practice, Chelmsford, Essex, UK
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Paquette DW, Fiorellini JP, Martuscelli G, Oringer RJ, Howell TH, McCullough JR, Reasner DS, Williams RC. Enantiospecific inhibition of ligature-induced periodontitis in beagles with topical (S)-ketoprofen. J Clin Periodontol 1997; 24:521-8. [PMID: 9266337 DOI: 10.1111/j.1600-051x.1997.tb00223.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Systemic and topical administration of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce periodontal disease progression in both animal models and human subjects. Our present research focuses on single enantiomers of these agents to examine whether enantiospecific therapy will be efficacious in slowing periodontitis. The purpose of this study was to evaluate the inhibitory effects of (S)-ketoprofen on experimentally induced alveolar bone loss in beagle dogs. 16, 18-month-old, female beagles were brought to optimal periodontal health over a 2-week pretreatment period. Experimental periodontitis was then induced by placing silk ligatures around premolar and molar teeth and by instituting a soft, plaque-promoting diet. At baseline, animals were randomized to 1 of 4 groups, consisting of 2x daily administration of (1) placebo dentifrice, (2) 0.3% (S)-ketoprofen dentifrice, (3) 3.0% (S)-ketoprofen dentifrice, or (4) 10.0 mg (S)-ketoprofen capsules (p.o.) over a 60 day treatment period. Standardized, periapical radiographs exposed at days 1 and 60 were analyzed by computer-assisted digital radiography in order to assess the rate of alveolar bone loss. Secondary outcomes included technetium 99m-tin-diphosphonate (99mTc-Sn-MDP) uptake and the gingival index. At baseline, no differences were observed among the groups for linear bone height or 99mTc-Sn-MDP uptake ratios. From days 1 to 60, cohorts differed significantly in terms of bone loss rates (p < 0.001). In particular, beagles treated with systemic or topical (S)-ketoprofen (0.3% or 3.0% dentifrices) exhibited significantly lower mean rates of bone loss compared to placebo treated beagles (p < 0.05). Group differences in mean radiopharmaceutical uptake ratio changes approached significance (ANOVA, p = 0.07), where animals treated with topical 0.3% (S)-ketoprofen demonstrated a reduction and other groups demonstrated elevations over the 60-day dosing period. Treatment cohorts did differ significantly with respect to changes in mean gingival indices (p < 0.05). Animals treated with 0.3% or 3.0% (S)-ketoprofen dentifrice exhibited significantly reduced elevations in gingival index scores as compared to placebo treated animals. These data provide evidence that enantiospecific therapy with (S)-ketoprofen, topically or systemically delivered, may alter the progression of periodontal disease in the beagle dog model.
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Affiliation(s)
- D W Paquette
- Department of Periodontics, University of North Carolina School of Dentistry, Chapel Hill, USA.
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Gemmell E, Marshall RI, Seymour GJ. Cytokines and prostaglandins in immune homeostasis and tissue destruction in periodontal disease. Periodontol 2000 1997; 14:112-43. [PMID: 9567968 DOI: 10.1111/j.1600-0757.1997.tb00194.x] [Citation(s) in RCA: 274] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- E Gemmell
- Department of Oral Biology, School of Dentistry, University of Queensland, Australia
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Offenbacher S, Salvi GE, Beck JD, Williams RC. The design and implementation of trials of host modulation agents. ANNALS OF PERIODONTOLOGY 1997; 2:199-212. [PMID: 9151554 DOI: 10.1902/annals.1997.2.1.199] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Over the last two decades it has become more evident that although oral microorganisms are essential agents of periodontal pathogenesis, interpatient variability in the host response is a major determinant of the expression of periodontal disease extent and severity. Data from animal models and human studies have identified many of the components of the host inflammatory response which serve as critical mediators of clinical inflammation, attachment loss, and bone resorption. Studies suggest that certain pharmacologic agents, which act at a molecular level to block specific inflammatory mediators, appear to attenuate disease progression. These promising findings herald a new era in periodontal medicine. Anti-infective therapies may soon be supplemented with anti-inflammatory pharmacological agents. However, there are many unanswered issues regarding formulation design, clinical application, potential indication claims, and clinical study design. Furthermore, current considerations of fundamental mechanisms of pathogenesis, as well as new data from epidemiologic studies emphasizing the multifactorial nature of disease, are changing the underlying assumptions which have served to guide our design of anti-infective drug trials over the last two decades. There are new questions regarding appropriate outcome measurements which are to be reconsidered. For example, the measurement of a change in periodontal disease status, either during progression or in response to therapy, is fundamentally unidimensional and may be only mildly informative when one considers that the disease is multifactorial by nature. Using an example from intensive care medicine, pathophysiologic studies of septic shock have demonstrated that the microbial dose and the host inflammatory mediator response are far better predictors of patient morbidity and mortality than any combination of clinical signs associated with clinical shock. Clinical trials of anti-cytokine and anti-inflammatory drugs to treat shock are now designed and conducted taking strategic advantage of this knowledge by including measurements of microbial dose and host response. It appears prudent that the design and implementation of clinical trials of host modulation agents also benefit from our current insights into pathogenesis and not represent a template-driven adaptation of historical, anti-infective clinical trial protocols.
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Affiliation(s)
- S Offenbacher
- School of Dentistry, University of North Carolina, Chapel Hill, USA
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Affiliation(s)
- C H Drisko
- Department of Periodontics, Endodontics, and Dental Hygiene, University of Louisville, Kentucky, USA
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Li KL, Vogel R, Jeffcoat MK, Alfano MC, Smith MA, Collins JG, Offenbacher S. The effect of ketoprofen creams on periodontal disease in rhesus monkeys. J Periodontal Res 1996; 31:525-32. [PMID: 8971650 DOI: 10.1111/j.1600-0765.1996.tb00516.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Ketoprofen creams were evaluated for the treatment of periodontal disease in a placebo-controlled, double-blind study in the rhesus monkeys, Macaca mulatta. Two formulations containing ketoprofen (1%), with or without vitamin E, were evaluated against appropriate controls (8 monkeys per group). Two weeks prior to treatment, the animals received prophylaxis on only the left side of the mouth (spontaneous model). Selected teeth on the right side of the mouth were ligated (ligature model). The creams were administered to the gingiva once daily at a standard dose of 1.8 ml per monkey for 6 months. Clinical assessments were made 2 wk before initiation, at baseline and 1, 2, 3 and 6 months post-treatment. The clinical parameters included plaque formation, gingival redness, edema, bleeding on probing and Ramfjord Attachment Level measurements (RAL). Radiographs were taken at 2 wk before initiation, baseline and at 3 and 6 months post-treatment. Digital, subtraction radiography was used to measure vertical linear bone loss along the interproximal root surfaces of the left and right mandibular first molars. Gingival crevicular fluid (GCF) was collected for biochemical assays on PGE2, TxB2, LTB4, IL-1 beta and TNF alpha. There were no significant differences among groups with respect to gingival indices. Radiographic data demonstrated significant positive effects on bone activity in both groups treated with ketoprofen formulations with improvement over time in the ligature model (0.01 < or = p < or = 0.04). The placebo group exhibited bone loss of 1.96 +/- 0.48 and 1.40 +/- 0.56 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream showed an apparent bone gain of 0.28 +/- 0.41 and 0.78 +/- 0.47 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream containing vitamin E showed a mean bone loss of 0.41-0.48 mm per site at 3 months with improvement to an apparent bone gain of 0.31 +/- 0.44 mm per site at 6 months. The biochemical data demonstrated early and significant suppression of GCF-LTB4 by both ketoprofen formulations at 1 month, which preceded the significant suppression of GCF-PGE2 at 2 and 3 months in the ligature model (p < 0.003) and at 2 to 6 months in the spontaneous model (p < 0.02). We conclude that ketoprofen at 1% level in suitable topical vehicles can effectively inhibit GCF-LTB4 and GCF-PGE2 and positively alter alveolar bone activity in the ligature-induced model of periodontitis in the monkey.
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Affiliation(s)
- K L Li
- Block Drug Company, Inc., Jersey City, NJ, USA
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Jendresen MD, Allen EP, Bayne SC, Donovan TE, Hansson TL, Klooster J, Kois JC. Annual review of selected dental literature: report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry. J Prosthet Dent 1994; 72:39-77. [PMID: 8083840 DOI: 10.1016/0022-3913(94)90214-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
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Heasman PA, Seymour RA, Kelly PJ. The effect of systemically-administered flurbiprofen as an adjunct to toothbrushing on the resolution of experimental gingivitis. J Clin Periodontol 1994; 21:166-70. [PMID: 8157768 DOI: 10.1111/j.1600-051x.1994.tb00298.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely researched in an attempt to control periodontal diseases. This double-blind parallel group study investigated the effect of a systemic flurbiprofen preparation (100 mg daily), when combined with toothbrushing on the resolution of experimental gingivitis in human volunteers. 47 volunteers abstained from tooth cleaning for 21 days. On day 21, 23 subjects were prescribed 100 mg of flurbiprofen daily whereas 24 subjects were prescribed placebo. In both groups, toothbrushing was re-introduced and all subjects used the Bass technique for 2 min each day. Both treatment regimens were continued for 7 days. Plaque indices, gingival indices and gingival crevicular fluid flow were assessed at baseline (day 0) and on days 21 and 27. There were no significant differences at p = 0.05 between the groups for plaque indices or gingival crevicular fluid flow. The flurbiprofen group, however, demonstrated greater resolution of gingival inflammation by day 27 when compared to the placebo controls (p = 0.04). The plasma levels of flurbiprofen in the test group showed mean concentrations of flurbiprofen of 4.7 (+/- 2.1) micrograms/ml at 1 h after dosing. After 6 h, this had fallen to 4.4 (+/- 1.6) micrograms/ml. It is concluded that these serum concentrations of flurbiprofen are sufficient to produce significant anti-inflammatory effects in the gingival tissues.
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Affiliation(s)
- P A Heasman
- Department of Operative Dentistry, Dental School, University of Newcastle upon Tyne, UK
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