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1
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Bagwe S, Mehta V, Mathur A, Kumbhalwar A, Bhati A. Role of various pharmacologic agents in alveolar bone regeneration: A review. Natl J Maxillofac Surg 2023; 14:190-197. [PMID: 37661974 PMCID: PMC10474547 DOI: 10.4103/njms.njms_436_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 10/21/2021] [Accepted: 11/02/2021] [Indexed: 09/05/2023] Open
Abstract
Alveolar bone and gingiva are components of the periodontium that house the tooth. It constantly adapts itself to the masticatory forces and position of the tooth. However, localized diseases like chronic periodontitis and certain systemic diseases destroy periodontal tissues, which include the alveolar bone. Various pharmacological agents are being explored for their pleiotropic properties to combat the destruction of alveolar bone. This review focuses on the role of pharmacological agents in alveolar bone regeneration.
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Affiliation(s)
| | - Vini Mehta
- Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
| | - Ankita Mathur
- Department of Periodontology, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, India
| | - Abhishek Kumbhalwar
- Research Consultant, STAT SENSE, Srushti 10, Sector 1 D, Amba Township Pvt. Ltd., Trimandir, Adalaj, Gujarat, India
| | - Ashok Bhati
- Department of Preventive Dental Sciences, College of Dentistry, Jazan University, Saudi Arabia
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2
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Sahingur SE. Dr. Marjorie K. Jeffcoat - A renaissance woman in oral health sciences and education. Oral Dis 2023; 29 Suppl 1:890-892. [PMID: 36651599 DOI: 10.1111/odi.14505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 12/29/2022] [Accepted: 01/09/2023] [Indexed: 01/19/2023]
Affiliation(s)
- Sinem Esra Sahingur
- Department of Periodontics, University of Pennsylvania, School of Dental Medicine, Philadelphia, Pennsylvania, USA
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3
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Aminu N, Chan SY, Mumuni MA, Umar NM, Tanko N, Zauro SA, Aminu A, Toh SM. Physicochemical compatibility studies of triclosan and flurbiprofen with excipients of pharmaceutical formulation using binary, ternary, and multi-combination approach. FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES 2021. [DOI: 10.1186/s43094-021-00302-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Abstract
Background
The aim of the study was to evaluate the suitability of triclosan (TCS) and flurbiprofen (FLB) with poly-ε-caprolactone (PCL), chitosan (CS), and Kolliphor® P188 (KP) for possible application in the design of nano-formulations.
Results
Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM) revealed the physical characteristics of the various sample compositions without any apparent interaction. The Fourier transform infrared spectroscopy (FTIR)’s spectra of the physical mixtures showed their characteristic absorption bands with broadening and overlapping of bands in some instances, but no appearance of new bands was observed.
Conclusion
The study revealed the physical form stability of the evaluated components after the storage period and lack of definite pharmaceutical incompatibility between them. Thus, the selected drugs and excipients could be used for the development of pharmaceutical nano-formulations.
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4
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Reddy M. A Tribute to the Enduring Lessons of Marjorie Jeffcoat. J Dent Res 2021. [DOI: 10.1177/00220345211001360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
- M.S. Reddy
- UCSF School of Dentistry, Oral Health Affairs, University of California San Francisco, San Francisco, CA, USA
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The Effects of Prednisone/Ketoprofen Administration in Association with Amoxicillin Clavulanate Following Periodontal Surgical Therapy in Patients with Severe Chronic Periodontitis. ACTA ACUST UNITED AC 2021; 57:medicina57050447. [PMID: 34064493 PMCID: PMC8147920 DOI: 10.3390/medicina57050447] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 04/25/2021] [Accepted: 04/28/2021] [Indexed: 11/23/2022]
Abstract
Background and Objectives: The aim of this study was to evaluate and compare the effects of two different anti-inflammatory drugs (ketoprofen and prednisone) combined with an antibiotic (amoxicillin + clavulanic acid) and periodontal surgery on dental and periodontal parameters in patients with severe chronic periodontitis. In addition, salivary stress expressed by cortisol levels was assessed. Materials and Methods: An interventional study was performed on 22 periodontal subjects and 19 clinical healthy controls. The patients were divided in four groups, depending on treatment planning, as follows: eight patients received prednisone and antibiotherapy, associated with surgical periodontal therapy; seven patients received ketoprofen and antibiotherapy, associated with surgical periodontal therapy (group II); seven patients received only prednisone. Periodontal healthy patients underwent routine scaling and polishing. Bleeding on probing (BOP), dental mobility and salivary cortisol (ng/mL) were assessed before and after treatment. The means and standard deviations for the salivary cortisol levels (SCLs), dental and periodontal parameters were calculated for all groups using each patient as a unit of analysis. Results: Data analyses showed that the two different anti-inflammatory drugs associated with or without surgical therapy were efficient on inflammation periodontal parameters (BOP, dental mobility). Prednisone treatment alone was associated with a significant decrease of SCLs between pretreatment and post-treatment. Conclusions: In the present study, the effects of either of the anti-inflammatory drugs on inflammation evolution and salivary stress were comparable in patients undergoing antibiotherapy and surgical periodontal therapy.
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Relationship between periodontal status and disease activity in patients with ankylosing spondylitis. Reumatologia 2021; 59:35-40. [PMID: 33707794 PMCID: PMC7944957 DOI: 10.5114/reum.2021.103643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 02/02/2021] [Indexed: 11/17/2022] Open
Abstract
Objectives Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the spine and sacroiliac joints, characterized by enthesitis. Recent studies have investigated the relationship between AS and periodontitis. The aim of this study was to evaluate the periodontal status of patients with AS and to determine the factors affecting this. Material and methods The study included 200 AS patients, of which 129 were taking anti-tumour necrosis factor (TNF) drugs and 71 were taking non-steroid anti-inflammatory drugs (NSAID). Patients did not change their medication during the study. Disease activity was evaluated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), mobility with the Bath Ankylosing Spondylitis Metrology Index (BASMI), functional status with the Bath Ankylosing Spondylitis Functional Index (BASFI), enthesitis with the integrated Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), and quality of life with the Ankylosing Spondylitis Quality of Life (ASQoL) scale. Data related to erythrocyte sedimentation rate, and C-reactive protein were recorded from the hospital information system. The plaque index (PI), gingival index (GI), pocket depth (PD), attachment level (CAL) measurements, and bleeding index (BOP) were measured. Results The results showed that 35.5% of the AS patients had periodontitis, at a lower rate in the anti-TNF group than in the NSAID group, but the difference was not statistically significant. Periodontitis-related factors were found to be age, BASFI and BASMI. A significant relationship was found between MASES and BOP and GI. Conclusions This suggests that periodontitis may be an enthesis in AS. Nevertheless, further studies are needed to explain the mechanism of periodontitis in AS patients.
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7
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Kirschneck C, Wolf F, Cieplik F, Blanck-Lubarsch M, Proff P, Schröder A. Impact of NSAID etoricoxib on side effects of orthodontic tooth movement. Ann Anat 2020; 232:151585. [PMID: 32818660 DOI: 10.1016/j.aanat.2020.151585] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 07/03/2020] [Accepted: 07/22/2020] [Indexed: 01/20/2023]
Abstract
OBJECTIVES The non-steroidal anti-inflammatory drug etoricoxib is the most highly selective inhibitor of cyclooxygenase-2 available (344:1) and has been approved for postoperative pain therapy following dental interventions in Europe. At clinically relevant doses it has been reported to only have marginal effects on the velocity of orthodontic tooth movement (OTM). Its effects on associated dental root resorptions, osteoclastogenesis, trabecular number in the alveolar bone and periodontal bone loss during OTM, however, have not yet been investigated. MATERIAL AND METHODS 40 male Fischer344 rats were divided into four groups: 1.5ml tap water/day p.o. (control, 1), additional 7.8mg/kg/day etoricoxib (normal dose) for three (2) or seven (3) days/week and 13.1mg/kg/day (high dose) for seven days/week, respectively (4). After a week of premedication, OTM in anterior direction of the first left upper molar was performed for 28 days by means of a nickel-titanium coil spring (0.25N). We quantified OTM-associated dental root resorptions, osteoclastogenesis, trabecular number and periodontal bone loss by histomorphometrical, histochemical and μCT analyses of the disected tooth-bearing upper jaw sections. RESULTS After 28 days of OTM, associated reduction of trabecular number seemed to be slightly alleviated by high doses of etoricoxib, whereas no significant other etoricoxib effects in the doses administered could be detected regarding OTM-induced or -associated dental root resorptions, osteoclastogenesis or periodontal bone loss. CONCLUSIONS Dental root resorptions, osteoclastogenesis and periodontal bone loss during OTM in rats were not significantly affected by etoricoxib in the clinically relevant dosages investigated with only a slight inhibitory effect on bone remodelling to be expected at high dosages. Etoricoxib is therefore not suitable for the prevention of these detrimental effects, but could be a suitable analgesic during OTM, as it has been reported not to affect tooth movement.
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Affiliation(s)
| | - Franziska Wolf
- Department of Orthodontics, University Hospital Regensburg, Germany
| | - Fabian Cieplik
- Department of Operative Dentistry and Periodontology, University Hospital Regensburg, Germany
| | | | - Peter Proff
- Department of Orthodontics, University Hospital Regensburg, Germany
| | - Agnes Schröder
- Department of Orthodontics, University Hospital Regensburg, Germany
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Monisha M, Elengickal TJ, Ram SKM, Madhu ML, Raghuveeran M, Pillai RR. Attitude and Awareness of Dentists Practicing in Southern India Toward Non-steroidal Anti-inflammatory Drugs. J Pharm Bioallied Sci 2019; 11:S355-S359. [PMID: 31198368 PMCID: PMC6555374 DOI: 10.4103/jpbs.jpbs_33_19] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background: Pain management is an everyday challenge in dentistry. Analgesics are the group of drugs prescribed for effective pain management, of which nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed drugs. Selection of NSAIDs must be judiciously made considering their pharmacological properties and adverse effects. Aim: This study aimed to analyze the attitude toward analgesic prescription among practicing dentists and the awareness to update their knowledge about them. Materials and Methods: The study was carried out among 100 dental practitioners, where a questionnaire consisting of 16 questions was formulated based on the awareness of indication and contraindication, actual practice, and required future trends for updating the knowledge. The questionnaire was distributed among the practitioners; the answered questionnaire was collected and tabulated. Statistical analysis included χ2 test to evaluate the significance. Results: Of 100 dental practitioners, 63% prescribed drugs based on the diagnosis. Aceclofenac was found to be the effective drug in postoperative pain management, whereas paracetamol was considered to be the safest among NSAIDs in clinical conditions such as bleeding disorders, gastric irritation, chronic kidney disease, and during pregnancy. All practicing dentists showed their willingness to participate in awareness programs in updating their knowledge. Conclusion: This study showed that dental clinical practitioners are well aware of the drugs to be prescribed in different clinical conditions but pitfalls have been observed in areas of systemic complication, where continuous educational programs are needed to overcome the same.
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Affiliation(s)
- Maria Monisha
- Department of Oral Medicine and Radiology, Sree Mookambika Institute of Dental Sciences, Kanyakumari Tamil Nadu, India
| | - Tatu Joy Elengickal
- Department of Oral Medicine and Radiology, Sree Mookambika Institute of Dental Sciences, Kanyakumari Tamil Nadu, India
| | - Shashi Kiran Mohan Ram
- Department of Oral Medicine and Radiology, Sree Mookambika Institute of Dental Sciences, Kanyakumari Tamil Nadu, India
| | - Malu L Madhu
- Department of Pedodontics, Azeezia College of Dental Sciences and Research, Kollam, India
| | | | - Rahul Raveendran Pillai
- Department of Oral Medicine and Radiology, Sree Mookambika Institute of Dental Sciences, Kanyakumari Tamil Nadu, India
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Yamamoto S, Omori K, Mandai H, Nakayama M, Nakagawa S, Kobayashi H, Kunimine T, Yoshimura H, Sakaida K, Sako H, Ibaragi S, Yamamoto T, Maeda H, Suga S, Takashiba S. Fungal metabolite (+)-terrein suppresses IL-6/sIL-6R-induced CSF1 secretion by inhibiting JAK1 phosphorylation in human gingival fibroblasts. Heliyon 2018; 4:e00979. [PMID: 30519664 PMCID: PMC6260243 DOI: 10.1016/j.heliyon.2018.e00979] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 10/16/2018] [Accepted: 11/22/2018] [Indexed: 12/12/2022] Open
Abstract
Control of bacterial infection-induced inflammatory responses is one of the effective therapeutic approaches of periodontal diseases. Natural products such as lipid mediators and metabolites from microorganisms have been used for decreasing inflammation. We previously reported that (+)-terrein inhibited activation of STAT3 and ERK1/2 in interleukin-6 (IL-6) signaling cascade, leading to prevent vascular endothelial growth factor (VEGF) secretion in human gingival fibroblasts (HGFs). However, little is still known about the role of (+)-terrein on inflammatory responses. In this study, we provided the possibility of novel action that (+)-terrein inhibits activation of Janus-activated kinase 1 (JAK1), which has a central function in IL-6 signaling cascade, and alters expression of mRNAs and proteins induced by IL-6/soluble IL-6 receptor (sIL-6R) stimulation in HGFs. First, we performed PCR array to examine IL-6/sIL-6R-induced mRNA expression, and then expression of mRNA and protein of colony stimulating factor-1 (CSF1) and VEGF were clearly determined by quantitative RT-PCR and ELISA, respectively. Treatment with (+)-terrein suppressed expression of mRNA and protein of CSF1 and VEGF by IL-6/sIL-6R stimulation. Next, to test the effect of (+)-terrein on IL-6/sIL-6R signaling cascade, we demonstrated whether (+)-terrein affects phosphorylation of JAK1 and its downstream proteins, Akt and SHP-2. Western blotting revealed that (+)-terrein inhibited IL-6/sIL-6R-induced phosphorylation of JAK1, Akt, and SHP-2. Therefore, (+)-terrein suppresses IL-6/sIL-6R-induced expression of CSF1 and VEGF via inhibition of JAK1, Akt, and SHP-2. Based on our results, we suggest that (+)-terrein is a candidate compound for anti-inflammatory effect associated with IL-6 signaling.
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Affiliation(s)
- Satoshi Yamamoto
- Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8525, Japan
| | - Kazuhiro Omori
- Department of Periodontics and Endodontics, Okayama University Hospital, Okayama, 700-8558, Japan
- Corresponding author.
| | - Hiroki Mandai
- Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan
| | - Masaaki Nakayama
- Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8525, Japan
| | - Saki Nakagawa
- Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8525, Japan
| | - Hiroya Kobayashi
- Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8525, Japan
| | - Tadashi Kunimine
- Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan
| | - Hiroshi Yoshimura
- Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan
| | - Kyosuke Sakaida
- Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8525, Japan
| | - Hidefumi Sako
- Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8525, Japan
| | - Soichiro Ibaragi
- Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8525, Japan
| | - Tadashi Yamamoto
- Department of Periodontics and Endodontics, Okayama University Hospital, Okayama, 700-8558, Japan
| | - Hiroshi Maeda
- Department of Endodontics, Osaka Dental University, Osaka, 540-0008, Japan
| | - Seiji Suga
- Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, Okayama, 700-8530, Japan
| | - Shogo Takashiba
- Department of Pathophysiology-Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8525, Japan
- Corresponding author.
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10
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Mahendra J, Mahendra L, Svedha P, Cherukuri S, Romanos GE. Clinical and microbiological efficacy of 4% Garcinia mangostana
L. pericarp gel as local drug delivery in the treatment of chronic periodontitis: A randomized, controlled clinical trial. ACTA ACUST UNITED AC 2017; 8. [DOI: 10.1111/jicd.12262] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Accepted: 01/23/2017] [Indexed: 11/28/2022]
Affiliation(s)
- Jaideep Mahendra
- Department of Periodontology; Meenakshi Ammal Dental College; Meenakshi Academy of Higher Education and Research; Chennai India
| | - Little Mahendra
- Department of Periodontics; Annamalai University; Chidambaram India
| | - Priyadharshini Svedha
- Department of Periodontology; Meenakshi Ammal Dental College; Meenakshi Academy of Higher Education and Research; Chennai India
| | - Sandhya Cherukuri
- Department of Periodontology; Meenakshi Ammal Dental College; Meenakshi Academy of Higher Education and Research; Chennai India
| | - Georgios E. Romanos
- Department Of Periodontology; Stony Brook University; Stony Brook New York USA
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11
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Lee CT, Teles R, Kantarci A, Chen T, McCafferty J, Starr JR, Brito LCN, Paster BJ, Van Dyke TE. Resolvin E1 Reverses Experimental Periodontitis and Dysbiosis. THE JOURNAL OF IMMUNOLOGY 2016; 197:2796-806. [PMID: 27543615 DOI: 10.4049/jimmunol.1600859] [Citation(s) in RCA: 122] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 07/23/2016] [Indexed: 12/14/2022]
Abstract
Periodontitis is a biofilm-induced inflammatory disease characterized by dysbiosis of the commensal periodontal microbiota. It is unclear how natural regulation of inflammation affects the periodontal biofilm. Promoters of active resolution of inflammation, including resolvin E1 (RvE1), effectively treat inflammatory periodontitis in animal models. The goals of this study were 1) to compare periodontal tissue gene expression in different clinical conditions, 2) to determine the impact of local inflammation on the composition of subgingival bacteria, and 3) to understand how inflammation impacts these changes. Two clinically relevant experiments were performed in rats: prevention and treatment of ligature-induced periodontitis with RvE1 topical treatment. The gingival transcriptome was evaluated by RNA sequencing of mRNA. The composition of the subgingival microbiota was characterized by 16S rDNA sequencing. Periodontitis was assessed by bone morphometric measurements and histomorphometry of block sections. H&E and tartrate-resistant acid phosphatase staining were used to characterize and quantify inflammatory changes. RvE1 treatment prevented bone loss in ligature-induced periodontitis. Osteoclast density and inflammatory cell infiltration in the RvE1 groups were lower than those in the placebo group. RvE1 treatment reduced expression of inflammation-related genes, returning the expression profile to one more similar to health. Treatment of established periodontitis with RvE1 reversed bone loss, reversed inflammatory gene expression, and reduced osteoclast density. Assessment of the rat subgingival microbiota after RvE1 treatment revealed marked changes in both prevention and treatment experiments. The data suggest that modulation of local inflammation has a major role in shaping the composition of the subgingival microbiota.
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Affiliation(s)
- Chun-Teh Lee
- Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA 02142; and
| | - Ricardo Teles
- Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA 02142; and
| | - Alpdogan Kantarci
- Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA 02142; and
| | - Tsute Chen
- Department of Microbiology, The Forsyth Institute, Cambridge, MA 02142
| | - Jon McCafferty
- Department of Microbiology, The Forsyth Institute, Cambridge, MA 02142
| | - Jacqueline R Starr
- Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA 02142; and
| | | | - Bruce J Paster
- Department of Microbiology, The Forsyth Institute, Cambridge, MA 02142
| | - Thomas E Van Dyke
- Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA 02142; and
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12
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Chee B, Park B, Fitzsimmons T, Coates AM, Bartold PM. Omega-3 fatty acids as an adjunct for periodontal therapy-a review. Clin Oral Investig 2016; 20:879-94. [PMID: 26885664 DOI: 10.1007/s00784-016-1750-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Accepted: 02/10/2016] [Indexed: 12/24/2022]
Abstract
OBJECTIVES The aim of this article is to present an overview of omega-3 fatty acids, their anti-inflammatory properties and potential use as an adjunct for periodontal therapy. MATERIALS AND METHODS A general literature search was conducted to provide an overview of omega-3 fatty acids, their metabolism and anti-inflammatory properties. A more specific literature search of PubMed and EMBASE was conducted to identify articles dealing studies investigating the effects of omega-3 fatty acids in the treatment of periodontitis in animals and humans and included cross-sectional, longitudinal and intervention designs. RESULTS To date, there is good emerging evidence that dietary supplementation with fish oil may be of some benefit and this is enhanced if combined with aspirin. All clinical intervention studies to date have been on small sample sizes, and this indicates there is need for larger and more robust clinical trials to verify these initial findings. CONCLUSIONS Dietary supplementation with fish oil could be a cost-effective adjunctive therapy to the management of periodontal disease. CLINICAL RELEVANCE The host modulatory properties of omega-3 fatty acids warrant further assessment of their use as an adjunct in the management of periodontitis.
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Affiliation(s)
- B Chee
- Department of Dentistry, Colgate Australian Clinical Dental Research Centre, Dental School, University of Adelaide, Frome Road, Adelaide, SA, 5005, Australia
| | - B Park
- Department of Dentistry, Colgate Australian Clinical Dental Research Centre, Dental School, University of Adelaide, Frome Road, Adelaide, SA, 5005, Australia
| | - T Fitzsimmons
- Department of Dentistry, Colgate Australian Clinical Dental Research Centre, Dental School, University of Adelaide, Frome Road, Adelaide, SA, 5005, Australia
| | - A M Coates
- Alliance for Research in Exercise, Nutrition and Activity (ARENA), Sansom Institute for Health Research, Division of Health Sciences, University of South Australia, Adelaide, SA, Australia
| | - P M Bartold
- Department of Dentistry, Colgate Australian Clinical Dental Research Centre, Dental School, University of Adelaide, Frome Road, Adelaide, SA, 5005, Australia.
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13
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Kang EH, Lee JT, Lee HJ, Lee JY, Chang SH, Cho HJ, Choi BY, Ha YJ, Park KU, Song YW, Van Dyke TE, Lee YJ. Chronic Periodontitis Is Associated With Spinal Dysmobility in Patients With Ankylosing Spondylitis. J Periodontol 2015; 86:1303-13. [PMID: 26291296 DOI: 10.1902/jop.2015.150202] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Although microbes have been suggested to play a role in the pathogenesis of ankylosing spondylitis (AS), several studies present contradictory results regarding the association between AS and chronic periodontitis (CP). METHODS Clinical, laboratory, and medication data were collected from 84 patients with AS and 84 age- and sex-matched controls. Periodontal measurements, including probing depths (PDs), clinical attachment loss (AL), serum anti-Porphyromonas gingivalis titers, and the detection of P. gingivalis DNA in gingival crevicular fluid, were recorded. All participants with periodontitis with PD ≥4 to <7 mm received scaling and root planing and were re-evaluated at 12 weeks; those still exhibiting periodontitis with PD of ≥4 to <7 mm at 12 weeks were followed at 24 weeks. RESULTS The prevalence of moderate-to-severe CP was not different between patients with AS and controls (70.2% versus 66.6%). The P. gingivalis detection rate was not different between patients with AS and controls or between patients with AS receiving and not receiving anti-tumor necrosis factor (TNF)-α agents. However, CP was positively associated with impaired spinal mobility of patients with AS in multivariate analyses. After periodontal treatment, PD and AL levels were improved in both groups, but the change was significantly greater in patients with AS than in controls. Patients with AS receiving anti-TNF-α agents exhibited a greater improvement in PD and AL than those who did not. CONCLUSIONS Although AS was not associated with the presence of CP, CP was associated positively with the severity of spinal dysmobility in Korean patients with AS. These results suggest that periodontitis can have a negative effect on axial movement in AS.
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Affiliation(s)
- Eun Ha Kang
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jung Tae Lee
- Department of Periodontology, Section of Dentistry, Seoul National University Bundang Hospital
| | - Hyo-Jung Lee
- Department of Periodontology, Section of Dentistry, Seoul National University Bundang Hospital
| | - Joo Youn Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Sung Hae Chang
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Hyon Joung Cho
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Byoong Yong Choi
- Department of Internal Medicine, Seoul Medical Center Public Corporation, Seoul, Korea
| | - You-Jung Ha
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kyoung Un Park
- Department of Laboratory Medicine, Seoul National University Bundang Hospital
| | - Yeong Wook Song
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Thomas E Van Dyke
- Department of Applied Oral Sciences, Forsyth Institute, Cambridge, MA
| | - Yun Jong Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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14
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Clinical effect of locally delivered gel containing green tea extract as an adjunct to non-surgical periodontal treatment. Odontology 2014; 104:89-97. [PMID: 25523604 DOI: 10.1007/s10266-014-0190-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Accepted: 12/01/2014] [Indexed: 10/24/2022]
Abstract
UNLABELLED Green tea catechins had an in vitro antibacterial effect against periodontopathic bacteria and were able to inhibit destruction of the periodontal tissue. In this study, we aimed to evaluate the effect of locally delivered gel containing green tea extract as an adjunct to non-surgical periodontal treatment. Forty-eight subjects who had teeth with probing pocket depth of 5-10 mm were randomly allocated into the test or control group. Probing pocket depth, clinical attachment level, gingival index (GI), bleeding on probing (BOP) and full mouth plaque score were measured at baseline. Subjects received oral hygiene instruction, single episode of scaling and root planing and subgingival application of the green tea gel (test group) or the placebo gel (control group). The gel was repeatedly applied at 1 and 2 weeks later. The parameters were recorded again at the 1st, 3rd and 6th month after the last gel application. The results showed that all parameters were improved in both groups compared to baseline. The test group exhibited significantly higher reduction in BOP at the 3rd month (p = 0.003) and significantly lower GI at the 1st month (p < 0.001) and 3rd month (p < 0.001) when compared with the control group. Thus, green tea gel could provide a superior benefit in reducing bleeding on probing and gingival inflammation when used as an adjunct to non-surgical periodontal treatment. ( TRIAL REGISTRATION MU-IRB 2008/153.0511, ClinicalTrials.gov NCT00918060).
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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: 6] [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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Tariq M, Iqbal Z, Ali J, Baboota S, Parveen R, Mirza M, Ahmad S, Sahni J. Development and Validation of a Stability-Indicating High-Performance Thin-Layer Chromatographic Method for the Simultaneous Quantification of Sparfloxacin and Flurbiprofen in Nanoparticulate Formulation. JPC-J PLANAR CHROMAT 2014. [DOI: 10.1556/jpc.27.2014.2.10] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Teles R, Teles F, Frias-Lopez J, Paster B, Haffajee A. Lessons learned and unlearned in periodontal microbiology. Periodontol 2000 2014; 62:95-162. [PMID: 23574465 PMCID: PMC3912758 DOI: 10.1111/prd.12010] [Citation(s) in RCA: 242] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Periodontal diseases are initiated by bacterial species living in polymicrobial biofilms at or below the gingival margin and progress largely as a result of the inflammation elicited by specific subgingival species. In the past few decades, efforts to understand the periodontal microbiota have led to an exponential increase in information about biofilms associated with periodontal health and disease. In fact, the oral microbiota is one of the best-characterized microbiomes that colonize the human body. Despite this increased knowledge, one has to ask if our fundamental concepts of the etiology and pathogenesis of periodontal diseases have really changed. In this article we will review how our comprehension of the structure and function of the subgingival microbiota has evolved over the years in search of lessons learned and unlearned in periodontal microbiology. More specifically, this review focuses on: (i) how the data obtained through molecular techniques have impacted our knowledge of the etiology of periodontal infections; (ii) the potential role of viruses in the etiopathogenesis of periodontal diseases; (iii) how concepts of microbial ecology have expanded our understanding of host-microbe interactions that might lead to periodontal diseases; (iv) the role of inflammation in the pathogenesis of periodontal diseases; and (v) the impact of these evolving concepts on therapeutic and preventive strategies to periodontal infections. We will conclude by reviewing how novel systems-biology approaches promise to unravel new details of the pathogenesis of periodontal diseases and hopefully lead to a better understanding of their mechanisms.
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Preventive Effects of a Kampo Medicine, Kakkonto, on Inflammatory Responses via the Suppression of Extracellular Signal-Regulated Kinase Phosphorylation in Lipopolysaccharide-Treated Human Gingival Fibroblasts. ISRN PHARMACOLOGY 2014; 2014:784019. [PMID: 24693448 PMCID: PMC3945151 DOI: 10.1155/2014/784019] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2013] [Accepted: 01/08/2014] [Indexed: 12/04/2022]
Abstract
Periodontal disease is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss in severe clinical cases. The chemical mediator prostaglandin E2 (PGE2) and cytokines such as interleukin- (IL-)6 and IL-8 have been known to play important roles in inflammatory responses and tissue degradation. In the present study, we investigated the effects of a kampo medicine, kakkonto (TJ-1), on the production of prostaglandin E2 (PGE2), IL-6, and IL-8 by human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) from Porphyromonas gingivalis. Kakkonto concentration dependently suppressed LPS-induced PGE2 production but did not alter basal PGE2 levels. In contrast, kakkonto significantly increased LPS-induced IL-6 and IL-8 production. Kakkonto decreased cyclooxygenase- (COX-)1 activity to approximately 70% at 1 mg/mL but did not affect COX-2 activity. Kakkonto did not affect cytoplasmic phospholipase A2 (cPLA2), annexin1, or LPS-induced COX-2 expression. Kakkonto suppressed LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation, which is known to lead to ERK activation and cPLA2 phosphorylation. These results suggest that kakkonto decreased PGE2 production by inhibition of ERK phosphorylation which leads to inhibition of cPLA2 phosphorylation and its activation. Therefore, kakkonto may be useful to improve gingival inflammation in periodontal disease.
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Shiloah J, Bland PS, Scarbecz M, Patters MR, Stein SH, Tipton DA. The effect of long-term aspirin intake on the outcome of non-surgical periodontal therapy in smokers: a double-blind, randomized pilot study. J Periodontal Res 2013; 49:102-9. [DOI: 10.1111/jre.12085] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/09/2013] [Indexed: 01/18/2023]
Affiliation(s)
- Jacob Shiloah
- Department of Periodontology; College of Dentistry; University of Tennessee Health Science Center; Memphis TN USA
| | - Paul S. Bland
- Department of Periodontology; College of Dentistry; University of Tennessee Health Science Center; Memphis TN USA
| | - Mark Scarbecz
- Department of Periodontology; College of Dentistry; University of Tennessee Health Science Center; Memphis TN USA
| | - Mark R. Patters
- Department of Periodontology; College of Dentistry; University of Tennessee Health Science Center; Memphis TN USA
| | - Sydney H. Stein
- Department of Periodontology; College of Dentistry; University of Tennessee Health Science Center; Memphis TN USA
| | - David A. Tipton
- Department of Periodontology; College of Dentistry; University of Tennessee Health Science Center; Memphis TN USA
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Koontongkaew S, Meesuk L, Aupaphong V, Ayudhaya TDN, Poachanukoon O. Inhibitory effect of Zingiber cassumunar extracts on lipopolysaccharide-induced cyclooxygenase-2 and matrix metalloproteinase expression in human gingival fibroblasts. J Periodontal Res 2012; 48:507-16. [PMID: 23278498 DOI: 10.1111/jre.12033] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/19/2012] [Indexed: 11/27/2022]
Abstract
BACKGROUND AND OBJECTIVE Lipopolysaccharides (LPS) induce the production of proinflammatory mediators such as prostaglandins and matrix metalloproteinases (MMPs) in human gingival fibroblasts (HGFs). Zingiber cassumunar is a medicinal plant that possesses anti-inflammatory properties. The aim of this study was to determine the effects of the Z. cassumunar extract on the expression of cyclooxygenase (COX)-1, COX-2 and MMP-2 in HGFs challenged with LPS. MATERIAL AND METHODS HGFs were treated with LPS in the presence or absence of Z. cassumunar extracts. The levels of expression of COX-1, COX-2 and MMP-2 mRNAs and of COX-1, COX-2 and MMP-2 proteins were detected by reverse transcription-polymerase chain reaction and western blotting, respectively. MMP-2 activities in cell-culture supernatants were determined using gelatin zymography. MAPK activation was evaluated by western blotting. RESULTS LPS treatment of HGFs resulted in the activation of ERK1/2, p38 and JNK. Z. cassumunar extracts significantly inhibited the phosphorylation of ERK1/2 and JNK in HGFs stimulated with LPS. A lesser inhibitory effect was observed for the phosphorylation of p38. RT-PCR and western blot analyses showed that Z. cassumunar extracts inhibited the LPS-induced expression of COX-2 mRNA and COX-2 protein, respectively, but not of COX-1 mRNA or COX-1 protein. Pretreatment of HGFs with Z. cassumunar also attenuated the induction of MMP-2 with LPS. CONCLUSION Our results indicate that Z. cassumunar extracts inhibit COX-2 and MMP-2 production by LPS-activated human gingival fibroblasts through blocking the proinflammatory signaling pathway involving ERK1/2, JNK and p38.
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Affiliation(s)
- S Koontongkaew
- Oral Biology Laboratory, Faculty of Dentistry, Thammasat University, Klong Luang, Prathumthani, Thailand.
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Gu Y, Walker C, Ryan ME, Payne JB, Golub LM. Non-antibacterial tetracycline formulations: clinical applications in dentistry and medicine. J Oral Microbiol 2012; 4:19227. [PMID: 23071896 PMCID: PMC3471324 DOI: 10.3402/jom.v4i0.19227] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2012] [Revised: 09/06/2012] [Accepted: 09/11/2012] [Indexed: 12/22/2022] Open
Abstract
In 1983, it was first reported that tetracyclines (TCs) can modulate the host response, including (but not limited to) inhibition of pathologic matrix metalloproteinase (MMP) activity, and by mechanisms unrelated to the antibacterial properties of these drugs. Soon thereafter, strategies were developed to generate non-antibacterial formulations (subantimicrobial-dose doxycycline; SDD) and compositions (chemically modified tetracyclines; CMTs) of TCs as host-modulating drugs to treat periodontal and other inflammatory diseases. This review focuses on the history and rationale for the development of: (a) SDD which led to two government-approved medications, one for periodontitis and the other for acne/rosacea and (b) CMTs, which led to the identification of the active site of the drugs responsible for MMP inhibition and to studies demonstrating evidence of efficacy of the most potent of these, CMT-3, as an anti-angiogenesis agent in patients with the cancer, Kaposi's sarcoma, and as a potential treatment for a fatal lung disease (acute respiratory distress syndrome; ARDS). In addition, this review discusses a number of clinical studies, some up to 2 years' duration, demonstrating evidence of safety and efficacy of SDD formulations in humans with oral inflammatory diseases (periodontitis, pemphigoid) as well as medical diseases, including rheumatoid arthritis, post-menopausal osteopenia, type II diabetes, cardiovascular diseases, and a rare and fatal lung disease, lymphangioleiomyomatosis.
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Affiliation(s)
- Ying Gu
- Department of General Dentistry, School of Dental Medicine, Stony Brook Medicine, Stony Brook University, Stony Brook, NY, USA
| | - Clay Walker
- Department of Oral Biology, School of Dental Medicine, University of Florida at Gainesville, Gainesville, FL, USA
| | - Maria E. Ryan
- Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook Medicine, Stony Brook University, Stony Brook, NY, USA
| | - Jeffrey B. Payne
- Department of Surgical Specialties, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE, USA
| | - Lorne M. Golub
- Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook Medicine, Stony Brook University, Stony Brook, NY, USA
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Srinivas M, Medaiah S, Girish S, Anil M, Pai J, Walvekar A. The effect of ketoprofen in chronic periodontitis: A clinical double-blind study. J Indian Soc Periodontol 2011; 15:255-9. [PMID: 22028513 PMCID: PMC3200022 DOI: 10.4103/0972-124x.85670] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2011] [Accepted: 08/21/2011] [Indexed: 11/21/2022] Open
Abstract
Background: The objective of this double-blind clinical trial was to evaluate the effects of the nonsteroidal anti-inflammatory drug (NSAID), ketoprofen, on patients with chronic periodontitis. Materials and Methods: Two similar local drug delivery preparations of a poloxamen gel containing 1.5% ketoprofen and a placebo were indigenously prepared for this purpose. Ten subjects aged 33-55 years with moderate to severe chronic periodontitis were recruited and were monitored for a period of 90 days. Three sites in each patient (total 30 sites) with a probing pocket depth of 5-8 mm were selected and divided randomly into three groups: 1) group A: scaling and rootplaning (SRP) + drug A; 2) group B: SRP + drug B; and 3) group C: SRP. Clinical parameters and blood smear (from intracrevicular blood) were assessed to determine the differential count and Arneth index. All parameters were assessed at baseline, 30 days and 90 days, respectively. Results: Highly significant values were achieved for plaque index (P=0.00), and significant values were obtained for gingival index (P=0.044). Reduction in bleeding on probing was found to be highly significant. Probing depth and clinical attachment level showed no inter group variation. Conclusion: The results of this double-blind trial indicate that the combined effect of locally delivered ketoprofen with SRP was more effective in controlling periodontal disease than SRP alone.
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Affiliation(s)
- M Srinivas
- Department of Periodontics, Coorg Institute of Dental Sciences, Coorg, Karnataka, India
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Al-Hezaimi K, Al-Askar M, Selamhe Z, Fu JH, Alsarra IA, Wang HL. Evaluation of novel adhesive film containing ketorolac for post-surgery pain control: a safety and efficacy study. J Periodontol 2010; 82:963-8. [PMID: 21138358 DOI: 10.1902/jop.2010.100553] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Prescribing analgesics after periodontal surgery is a common practice. However, it can become a challenge for patients with systemic diseases or who are on long-term medications. Ketorolac tromethamine (KT), a non-steroidal anti-inflammatory drug, is incorporated into an adhesive film to overcome the limitations associated with oral, intravenous, intramuscular, or sublingual routes of drug administration. This study evaluates the analgesic effect of a KT adhesive film for pain management after periodontal surgery. METHODS Aqueous solvents of two bioadhesive polymers (hydroxypropyl methylcellulose and polyacrylic acid), together with 30 mg of KT, were used to formulate the adhesive film. Sixty-eight patients, who each received a free gingival graft, were randomly divided into treatment and control groups. In the treatment group, the prepared adhesive film was applied over the surgical site, whereas in the control group adhesive film without KT was placed initially. Two hours after surgery, the KT adhesive film was applied on the surgical site in the control group. A visual analog scale was used to assess the degree of pain encountered at 0, 1, 2, 3, 4, 5, 24, and 48 hours post-surgery. RESULTS The treatment group reported a significant reduction of pain intensity during the first 2 hours after surgery (P <0.05). After the KT adhesive film was applied in the control group, pain intensity was reduced to a non-significant level by the third hour after surgery. No adverse reaction or undesirable gastrointestinal side effect was observed. CONCLUSION Adhesive film containing 30 mg of KT was effective in controlling post-surgical pain with no observable gastrointestinal effects.
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Affiliation(s)
- Khalid Al-Hezaimi
- Eng. A.B. Research Chair for Growth Factors and Bone Regeneration, Division of Periodontics, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
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Ara T, Honjo KI, Fujinami Y, Hattori T, Imamura Y, Wang PL. Preventive effects of a kampo medicine, orento on inflammatory responses in lipopolysaccharide treated human gingival fibroblasts. Biol Pharm Bull 2010; 33:611-6. [PMID: 20410594 DOI: 10.1248/bpb.33.611] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
In the present study, we investigated the effects of a Kampo medicine Orento (TJ-120) on the production of prostaglandin E(2) (PGE(2)), interleukin (IL)-6 and IL-8 by human gingival fibroblasts (HGFs) treated with lipopolysaccharide from Porphyromonas gingivalis (PgLPS). HGFs proliferation was dose-dependently decreased with Orento at days 3 and 7. However, treatment with PgLPS (10 ng/ml), Orento (up to 1 mg/ml) and their combinations for 24 h did not affect the viability of HGFs. Orento suppressed PgLPS-induced PGE(2) production in a dose-dependent manner but did not alter basal PGE(2) level. In contrast, Orento did not alter PgLPS-induced IL-6 and IL-8 productions. These alterations by Orento were similar to those by a mitogen-activated protein kinase kinase (MAPKK/MEK) inhibitor, PD98059. A Orento showed no effect on cyclooxygenase (COX)-1 and COX-2 activities, and increased cytoplasmic phospholipase A(2) (cPLA(2)) expression and increased PgLPS-induced COX-2 expression. Orento suppressed PgLPS-induced mobility retardation of cPLA(2) band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels, that is cPLA(2) phosphorylation and its activation, while Orento alone did not alter cPLA(2) phosphorylation. Orento suppressed PgLPS-induced extracellular signal-regulated kinase (ERK) phosphorylation, which is known to lead to ERK activation and cPLA(2) phosphorylation. These results suggest that Orento decreased PGE(2) production by inhibition of cPLA(2) phosphorylation and its activation via inhibition of ERK phosphorylation, and also that Orento may be useful to improve gingival inflammation in periodontal disease.
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Affiliation(s)
- Toshiaki Ara
- Department of Pharmacology, Matsumoto Dental University, Japan
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Nakazono Y, Ara T, Fujinami Y, Hattori T, Wang PL. Preventive Effects of a Kampo Medicine, Hangeshashinto on Inflammatory Responses in Lipopolysaccharide-Treated Human Gingival Fibroblasts. J HARD TISSUE BIOL 2010. [DOI: 10.2485/jhtb.19.43] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Karakawa A, Fukawa Y, Okazaki M, Takahashi K, Sano T, Amano H, Yamamoto M, Yamada S. Diclofenac sodium inhibits NFkappaB transcription in osteoclasts. J Dent Res 2009; 88:1042-7. [PMID: 19828894 DOI: 10.1177/0022034509346147] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
A non-steroidal anti-inflammatory drug, diclofenac, acts efficiently against inflammation; however, down-regulation of diclofenac on bone remodeling has raised concerns. The inhibitory mechanisms of diclofenac are poorly understood. We hypothesized that diclofenac down-regulates osteoclast differentiation and activation via inhibition of the translocation of phosphorylated nuclear factor kappa B (NFkappaB). When osteoclasts prepared from mouse hematopoietic stem cells were treated with diclofenac, tartrateresistant acid phosphatase-positive multinucleated cells decreased in a concentration-dependent manner. Pit formation assay revealed the abolition of osteoclastic bone resorption; levels of cathepsin K transcripts, an osteoclastic resorption marker, were down-regulated time-dependently. Diclofenac induced the accumulation of the inhibitor of kappa B in cytosol, which led to suppression of the nuclear translocation of NFkappaB and phosphorylated NFkappaB. These results suggest that the novel mechanism of diclofenac for bone remodeling is associated with phosphorylated NFkappaB reduction, which regulates osteoclast differentiation and activation.
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Affiliation(s)
- A Karakawa
- Department of Pharmacology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
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Pinho MDN, Pereira LB, de Souza SLS, Palioto DB, Grisi MFDM, Novaes AB, Taba M. Short-term effect of COX-2 selective inhibitor as an adjunct for the treatment of periodontal disease: a clinical double-blind study in humans. Braz Dent J 2009; 19:323-8. [PMID: 19180322 DOI: 10.1590/s0103-64402008000400007] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2008] [Accepted: 03/13/2008] [Indexed: 11/21/2022] Open
Abstract
Adjunctive therapeutic strategies that modulate the inflammatory mediators can play a significant role in periodontal therapy. In this double-blind, placebo-controlled study, 60 subjects diagnosed as periodontitis patients were evaluated for 28 days after periodontal treatment combined with selective cyclooxygenase-2 (COX-2) inhibitor. The experimental group received scaling and root planning (SRP) combined with the Loxoprofen antiinflammatory drug (SRP+Loxoprofen). The control group received SRP combined with placebo (SRP+placebo). Plaque index (PI), probing pocket depth (PD) and bleeding on probing (BOP) were monitored with an electronic probe at baseline and after 14 and 28 days. Both groups displayed clinical improvement in PD, PI and BOP. They also showed statistically similar values (p>0.05) of PD reduction on day 14 (0.4 mm) and on day 28 (0.6 mm). At the baseline, few deeper sites (>or=7 mm) from SRP+Loxoprofen group were responsible and most PD reduction was observed after 14 days (p<0.05). The percentage of remaining deep pockets (>or=7 mm) after 14 days in the SRP+Loxoprofen group was significantly lower (p<0.05) than in the SRP+placebo group. Loxoprofen presents potential effect as an adjunct of periodontal disease treatment, but long-term clinical trials are necessary to confirm its efficacy.
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Affiliation(s)
- Márcia de Noronha Pinho
- Department of Oral and Maxillofacial Surgery and Traumatology and Periodontology, Dental School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil
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Azoubel MCF, Sarmento VA, Cangussú V, Azoubel E, Bittencourt S, Cunha FQ, Ribeiro RA, Brito GAC. Adjunctive benefits of systemic etoricoxib in non-surgical treatment of aggressive periodontitis: short-term evaluation. J Periodontol 2008; 79:1719-25. [PMID: 18771374 DOI: 10.1902/jop.2008.080019] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND This pilot study assessed the effect of short-duration treatment with etoricoxib as adjuvant therapy to scaling and root planing (SRP) on the clinical and radiographic parameters and prostaglandin E(2) (PGE(2)) levels in aggressive periodontitis. METHODS Subjects were randomly allocated to test or control treatment (n = 10 in each group) and submitted to SRP and treatment with etoricoxib, 120 mg/day, or placebo for 7 days. Probing depth, clinical attachment level (CAL), gingival recession, visible plaque index, bleeding on probing, linear distance (LD) from the cemento-enamel junction to the alveolar crest, and analysis of the gray levels were recorded before and 1 month after the therapies. The prostaglandin E(2) (PGE(2)) level in the gingival crevicular fluid (GCF) was measured by radioimmunoassay at the beginning of the study and 7 and 30 days after treatment. RESULTS No significant difference in the clinical parameters was observed between the groups at the end of the experimental period, although both groups presented significant improvement in all variables examined. There was a decrease in CAL from 5.54 +/- 0.47 mm to 3.59 +/- 0.53 mm in the test group and from 5.92 +/- 1.10 mm to 3.69 +/- 0.80 mm in the control group. A significant reduction in PGE(2) was found after 7 days of treatment. LD differed between the groups. CONCLUSION Etoricoxib did not promote additional improvement in the clinical parameters; however, it produced an initial reduction in the PGE(2) levels in the GCF, which could be related to the discrete improvement in the bone condition.
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Affiliation(s)
- Maria Cecília F Azoubel
- Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
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Topical application of Garcinia mangostana L. pericarp gel as an adjunct to periodontal treatment. Complement Ther Med 2008; 16:262-7. [DOI: 10.1016/j.ctim.2007.12.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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Vardar-Sengul S, Buduneli E, Turkoglu O, Buduneli N, Atilla G, Wahlgren J, Sorsa T, Baylas H. The Effects of Selective COX-2 Inhibitor/Celecoxib and Omega-3 Fatty Acid on Matrix Metalloproteinases, TIMP-1, and Laminin-5γ2-Chain Immunolocalization in Experimental Periodontitis. J Periodontol 2008; 79:1934-41. [DOI: 10.1902/jop.2008.080001] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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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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Ara T, Maeda Y, Fujinami Y, Imamura Y, Hattori T, Wang PL. Preventive effects of a Kampo medicine, Shosaikoto, on inflammatory responses in LPS-treated human gingival fibroblasts. Biol Pharm Bull 2008; 31:1141-4. [PMID: 18520044 DOI: 10.1248/bpb.31.1141] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
In the present study, we investigated the anti-inflammatory effects of a Kampo medicine Shosaikoto (TJ-9) using in vitro periodontal disease model, in which human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) from Porphyromonas gingivalis (PgLPS) produce IL-6, IL-8 and prostaglandin E2 (PGE2). Treatment with PgLPS (10 ng/ml), TJ-9 (up to 1 mg/ml) and their combinations for 24 h did not affect the viability of HGFs. Moreover, TJ-9 did not alter LPS-induced IL-6 and IL-8 productions. However, TJ-9 significantly suppressed LPS-induced PGE2 production in a dose-dependent manner but TJ-9 alone did not affect basal PGE2 level. Western blotting demonstrated that TJ-9 decreased cyclooxygenase-2 (COX-2) expression in a dose-dependent manner but not phospholipase A2. Moreover, TJ-9 selectively and dose-dependently inhibited COX-2 activity. These results suggest that TJ-9 decreased PGE2 production by inhibition of both COX-2 expression and activity and that TJ-9 may be useful to improve gingival inflammation in periodontal disease.
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Affiliation(s)
- Toshiaki Ara
- Department of Pharmacology, Matsumoto Dental University, Shiojiri, Nagano, Japan
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Pablos AB, Ramalho SA, König B, Furuse C, de Araújo VC, Cury PR. Effect of meloxicam and diclofenac sodium on peri-implant bone healing in rats. J Periodontol 2008; 79:300-6. [PMID: 18251644 DOI: 10.1902/jop.2008.070301] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND This study evaluated the effects of diclofenac sodium and meloxicam on peri-implant bone healing. METHODS Thirty male rats were divided into three groups: the control group (CG) received no drug; the diclofenac sodium group (DSG) received 1.07 mg/kg twice a day for 5 days; and the meloxicam group (MG) received 0.2 mg/kg daily for 5 days. A screw-shaped titanium implant was placed in the tibia. Fluorochromes, oxytetracycline (OxT), calcein (CA), and alizarin (AL), were injected at 7, 14, and 21 days, respectively, after implantation, and the animals were sacrificed 28 days after implant placement. The percentages of OxT-, CA-, and AL-labeled bone as well as the percentages of bone-to-implant contact (BIC), cortical bone area (CBA), and trabecular bone area (TBA) within the implant threads were evaluated. RESULTS Bone healing was delayed in the DSG during the first 14 days after implant placement (OxT-labeled bone: DSG: 5.3% +/- 7.3% versus CG: 13.2% +/- 9.8%, P = 0.002, and versus MG:14.4% +/- 13.1%, P = 0.05). The percentages of BIC (DSG: 49.6% +/- 21.9%; MG: 67.1% +/- 22.8%; and CG: 68.1% +/- 22.8%) and CBA (DSG: 63.7% +/- 21.2%; MG: 82.7% +/- 12.4%; CG: 84.9% +/- 10.6%) were lower in the DSG compared to the MG and CG (P <0.001). The percentage of TBA was significantly greater in the DSG compared to the MG and CG (DSG: 36.3% +/- 21.2% versus MG: 17.3% +/- 12.7% and versus CG: 15.1% +/- 10.6%; P <0.001). CONCLUSION Diclofenac sodium seemed to delay peri-implant bone healing and to decrease BIC, whereas meloxicam had no negative effect on peri-implant bone healing.
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Affiliation(s)
- Alethéia B Pablos
- Department of Implantology, São Leopoldo Mandic Dental Research Center, Campinas, SP, Brazil.
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Luan Q, Desta T, Chehab L, Sanders V, Plattner J, Graves D. Inhibition of Experimental Periodontitis by a Topical Boron-based Antimicrobial. J Dent Res 2008; 87:148-52. [DOI: 10.1177/154405910808700208] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
AN0128 is a boron-containing compound with antibacterial and anti-inflammatory properties. To test its potential effectiveness in treating periodontal disease, we induced experimental periodontitis in the rat by placing ligatures and assessed the impact of AN0128 and positive and negative controls by micro-CT and histologic measurements. The formation of an inflammatory infiltrate was measured in hematoxylin-and-eosin-stained sections. Daily application of AN0128 (1%) compared with controls reduced bone loss by 38 to 44% (P < 0.05), while vehicle alone had no effect (P > 0.05). The reduction in bone loss with AN0128 was similar to that achieved with a NSAID, ketorolac, and Total toothpaste containing triclosan. AN0128 also reduced the level of gingival inflammation 42% compared with the ligature only (P < 0.05), whereas vehicle alone had no effect (P > 0.05). The results indicate that AN0128 significantly reduces the formation of an inflammatory infiltrate and reduces bone loss, measured histologically and by micro-CT.
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Affiliation(s)
- Q. Luan
- Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, Boston, MA 02118, USA
- Anacor Pharmaceuticals, Inc., Palo Alto, CA 94303, USA
- Department of Periodontology, Peking University School of Stomatology, Beijing, China 100081
| | - T. Desta
- Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, Boston, MA 02118, USA
- Anacor Pharmaceuticals, Inc., Palo Alto, CA 94303, USA
- Department of Periodontology, Peking University School of Stomatology, Beijing, China 100081
| | - L. Chehab
- Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, Boston, MA 02118, USA
- Anacor Pharmaceuticals, Inc., Palo Alto, CA 94303, USA
- Department of Periodontology, Peking University School of Stomatology, Beijing, China 100081
| | - V.J. Sanders
- Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, Boston, MA 02118, USA
- Anacor Pharmaceuticals, Inc., Palo Alto, CA 94303, USA
- Department of Periodontology, Peking University School of Stomatology, Beijing, China 100081
| | - J. Plattner
- Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, Boston, MA 02118, USA
- Anacor Pharmaceuticals, Inc., Palo Alto, CA 94303, USA
- Department of Periodontology, Peking University School of Stomatology, Beijing, China 100081
| | - D.T. Graves
- Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, Boston, MA 02118, USA
- Anacor Pharmaceuticals, Inc., Palo Alto, CA 94303, USA
- Department of Periodontology, Peking University School of Stomatology, Beijing, China 100081
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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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Kim DM, Koszeghy KL, Badovinac RL, Kawai T, Hosokawa I, Howell TH, Karimbux NY. The Effect of Aspirin on Gingival Crevicular Fluid Levels of Inflammatory and Anti-Inflammatory Mediators in Patients With Gingivitis. J Periodontol 2007; 78:1620-6. [PMID: 17668982 DOI: 10.1902/jop.2007.070011] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Inflammatory and anti-inflammatory mediators may play a significant role in patients with gingivitis. The purpose of this study was to assess the short-term effects of the systemic administration of two different concentrations of aspirin (81 and 325 mg/day, by mouth) on clinical periodontal parameters and gingival crevicular fluid (GCF) levels of 15-epi-lipoxin A4 (15-epi-LXA4), lipoxin A4, leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and interleukin (IL)-6 and -1beta in a sample of naturally occurring gingivitis patients. METHODS At day 0, after initial screening for entry, baseline periodontal parameters, including bleeding on probing (BOP), periodontal probing depths (PDs), and plaque index (PI) were measured, and GCF was sampled from 12 intrasulcular sites with filter paper strips for the measurement of six types of inflammatory and anti-inflammatory mediators using competitive enzyme immunoassay and enzyme-linked immunosorbent assay (prevalues). Forty-seven subjects were assigned randomly to one of three treatment groups: placebo (15 subjects); aspirin, 81 mg (16 subjects); and aspirin, 325 mg (16 subjects) once daily. On day 7, subjects were recalled for the measurement of periodontal parameters and collection of GCF samples for the measurement of six types of mediators (postvalues). RESULTS Changes in inflammatory and anti-inflammatory mediator levels were not statistically significant for any of the three treatment groups. However, when pre- and postvalues were compared in the subjects receiving aspirin, 325 mg, there was a negative trend in the relationship between 15-epi-LXA4 and PGE2, whereas the relationship between LTB4 and PGE2 was not as strong. This might indicate that the subjects responding to aspirin-mediated PGE2 suppression effects produced higher 15-epi-LXA4 in GCF than non-responders. No statistically significant differences in PD and PI between pre- and postvalues were found for any of the three treatment groups. However, the results demonstrated a significant increase in BOP when aspirin, 325 mg was compared to placebo (P <0.001) and aspirin, 81 mg (P = 0.001). CONCLUSIONS Aspirin can have an affect on BOP in naturally occurring gingivitis patients. Although most of the inflammatory mediators did not show significantly detectable changes after aspirin treatment for 7 days, the trend of aspirin-associated increases of 15-epi-LXA4 implied that this recently discovered aspirin-dependent eicosanoid may be associated with the increased incidence of BOP observed in the subjects who received aspirin therapy.
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Affiliation(s)
- David M Kim
- Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA.
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Abstract
Topically administered non-steroidal anti-inflammatory drugs (NSAIDs) inhibit periodontal bone loss, but little is known about the mechanism by which they penetrate oral epithelium. Active transporters could potentially play a role in this process. In this study, we used a cell line derived from oral epithelium to investigate a role for transporters and to characterize conditions that enhance epithelial penetration. Using fluorescence to monitor uptake, we demonstrated that SCC-25 cell monolayers transport naproxen with a Michaelis constant (K(m)) and maximum velocity (V(max)) of 164 microg/mL and 0.94 ng/min/microg protein, respectively. At steady state, the intra-cellular/extracellular concentration ratio was 3.4. Naproxen accumulation was more efficient at acidic pH than under neutral or alkaline conditions. Small proportions of glycerol, Pluronic F-127, and glucosylceramide enhanced naproxen entry. The individual and combined effects of glycerol and Pluronic F-127 were of lesser magnitude than those obtained with glucosylceramide or at pH 6.3. Thus, SCC-25 cells possess transporters for naproxen.
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Affiliation(s)
- R R Fitzgerald
- Section of Periodontology, College of Dentistry, The Ohio State University Health Sciences Center, 305 West 12th Avenue, P.O. Box 182357, Columbus, OH 43218-2357, USA
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Kirkwood KL, Cirelli JA, Rogers JE, Giannobile WV. Novel host response therapeutic approaches to treat periodontal diseases. Periodontol 2000 2007; 43:294-315. [PMID: 17214846 PMCID: PMC2570321 DOI: 10.1111/j.1600-0757.2006.00166.x] [Citation(s) in RCA: 129] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Keith L Kirkwood
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA
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Toker H, Marakoglu I, Poyraz O. Effect of meloxicam on gingival crevicular fluid IL-1beta and IL1 receptor antagonist levels in subjects with chronic periodontitis, and its effects on clinical parameters. Clin Oral Investig 2006; 10:305-10. [PMID: 16896836 DOI: 10.1007/s00784-006-0062-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2005] [Accepted: 06/13/2006] [Indexed: 11/25/2022]
Abstract
The aim of the present study was to determine the effects of meloxicam after initial periodontal treatment on interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1ra) in gingival crevicular fluid (GCF) and clinical parameters in the chronic periodontitis patients. Data were obtained from 30 patients with chronic periodontitis. Fifteen chronic periodontitis patients received 7.5 mg meloxicam, and 15 patients received placebo tablets in a 1x1 regimen for 1 month. All subjects were nonsmokers and had not received any periodontal therapy. The plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment level (CAL) were recorded. The GCF was collected using a paper strip: eluted and enzyme-linked immunoabsorbent assays (ELISAs) were performed to determine the cytokine levels. The clinical data and GCF samples were obtained after periodontal therapy and 1 month after periodontal therapy. The PI, GI, PD, and GCF IL-1ra decreased significantly (p<0.05) in meloxicam group at first month when comparing the initial levels. While decrease of the PI was statistically significant in control group (p<0.05), statistically significant changes were not determined in the other clinical parameters and GCF cytokine levels (p>0.05). There were no significant differences between two groups in any of the investigated parameters. Our observations did not reveal any influence of meloxicam on levels of IL-1beta and IL-1ra in chronic periodontitis. Additional clinical studies are advisable to determine whether COX-2 selective drugs alter periodontal disease outcome with greater safety.
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Affiliation(s)
- Hulya Toker
- Department of Periodontology, Cumhuriyet University Faculty of Dentistry, Sivas, 58140, Turkey.
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Tseng LL, Cheng HH, Huang CJ, Liu SI, Kuo CC, Chen WC, Huang JK, Hsu SS, Chang HT, Kao CH, Ho CM, Jan CR. Dual effect of flurbiprofen on cell proliferation and agonist-induced Ca(2+) movement in human osteosarcoma cells. Basic Clin Pharmacol Toxicol 2006; 98:160-7. [PMID: 16445589 DOI: 10.1111/j.1742-7843.2006.pto_279.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
In human MG63 osteosarcoma cells, the effect of flurbiprofen on intracellular Ca(2+) concentrations ([Ca(2+)](i)) and proliferation was explored. The proliferation was enhanced by 20-120 microM flurbiprofen, and was decreased by 140-200 microM flurbiprofen. The effect of flurbiprofen on the increases in cytosolic free Ca(2+) levels ([Ca(2+)](i)) induced by ATP, bradykinin, histamine and thapsigargin (an inhibitor of the endoplasmic reticulum Ca(2+) ATPase), was examined. In cell preincubated with 20 or 80 microM flurbiprofen, the [Ca(2+)](i) increases induced by all agonists were attenuated. In the presence of 20 microM flurbiprofen, the decreased [Ca(2+)](i) responses with the agonists were attributed to a defective Ca(2+) influx because this decrease was unobserved in agonists-induced [Ca(2+)](i) increases in the absence of extracellular Ca(2+). In the presence of 80 microM flurbiprofen, both the Ca(2+) influx component and the Ca(2+) releasing (from organelles) component were defective. These results suggest that flurbiprofen could alter proliferation and inhibit [Ca(2+)](i) increases.
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Affiliation(s)
- Li-Ling Tseng
- Department of Dentistry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 813
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Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are used to manage pain and inflammatory disorders. We hypothesized that gingival fibroblasts actively accumulate NSAIDs and enhance their levels in gingival connective tissue. Using fluorescence to monitor NSAID transport, we demonstrated that cultured gingival fibroblasts transport naproxen in a saturable, temperature-dependent manner with a K(m) of 127 mug/mL and a V(max) of 1.42 ng/min/mug protein. At steady state, the intracellular/extracellular concentration ratio was 1.9 for naproxen and 7.2 for ibuprofen. Naproxen transport was most efficient at neutral pH and was significantly enhanced upon cell treatment with TNF-alpha. In humans, systemically administered naproxen attained steady-state levels of 61.9 mug/mL in blood and 9.4 mug/g in healthy gingival connective tissue, while ibuprofen attained levels of 2.3 mug/mL and 1.5 mug/g, respectively. Thus, gingival fibroblasts possess transporters for NSAIDs that are up-regulated by an inflammatory mediator, but there is no evidence that they contribute to elevated NSAID levels in healthy gingiva.
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Affiliation(s)
- M.M. Zavarella
- Sections of Periodontology, The Ohio State University Health Sciences Center, 305 West 12th Avenue, P.O. Box 182357, Columbus, OH 43218-2357, USA
| | - O. Gbemi
- Oral Biology, College of Dentistry, The Ohio State University Health Sciences Center, 305 West 12th Avenue, P.O. Box 182357, Columbus, OH 43218-2357, USA
| | - J.D. Walters
- Sections of Periodontology, The Ohio State University Health Sciences Center, 305 West 12th Avenue, P.O. Box 182357, Columbus, OH 43218-2357, USA
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Affiliation(s)
- Robin A Seymour
- School of Dental Sciences, University of Newcastle upon Tyne, UK
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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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Vardar S, Buduneli E, Baylas H, Berdeli AH, Buduneli N, Atilla G. Individual and combined effects of selective cyclooxygenase-2 inhibitor and omega-3 fatty acid on endotoxin-induced periodontitis in rats. J Periodontol 2005; 76:99-106. [PMID: 15830643 DOI: 10.1902/jop.2005.76.1.99] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND The present study was planned to evaluate the individual and combined effects of selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, and omega-3 fatty acid on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), leukotriene B4 (LTB4), and platelet activating factor (PAF) in endotoxin-induced periodontitis in rats. METHODS Experimental periodontitis was induced by repeated injection of Escherichia coli endotoxin (LPS). Forty-four adult male Sprague-Dawley rats were divided into five study groups: saline control, LPS, celecoxib, omega-3 fatty acid, and combination celecoxib and omega-3 fatty acid. Celecoxib and omega-3 fatty acid were given either as a single agent or as a combination therapy during 14 days of the study period. At the end of the 2-week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE2, PGF2alpha, and LTB4 levels by enzyme immunoassay and for PAF levels by radioimmunoassay. The defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by using parametric tests. RESULTS LPS injection resulted in significantly more bone loss than the saline controls (P<0.05) and significant elevations in the gingival tissue levels of all the analyzed mediators except PGF2alpha. Individual administration of celecoxib revealed significant reductions in PGE2 and PAF levels (P <0.05), while omega-3 fatty acid provided significant reduction in PGE2, PGF2alpha, and LTB4 levels compared to the LPS group (P <0.05). Combined administration of celecoxib and omega-3 fatty acid exhibited significantly lower values than those of the LPS group in all the analyzed membrane phospholipid mediators (P <0.05), which approximated the levels in the saline control group (P>0.05). CONCLUSIONS The results of the present study indicate that celecoxib and omega-3 fatty acid, when used individually, show a rather partial effect on the control of the analyzed mediators, but when combined they show a synergic effect and provide significant reductions in the gingival tissue levels of PGE2, PGF2alpha, LTB4, and PAF in LPS-induced experimental periodontitis. These findings may pioneer further clinical human studies investigating the possible place of celecoxib and omega-3 fatty acid in periodontal treatment.
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Affiliation(s)
- Saynur Vardar
- School of Dentistry, Department of Periodontology, Ege University, Izmir, Turkey.
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Vardar S, Buduneli E, Türkoğlu O, Berdeli AH, Baylas H, Başkesen A, Atilla G. Therapeutic versus prophylactic plus therapeutic administration of omega-3 fatty acid on endotoxin-induced periodontitis in rats. J Periodontol 2005; 75:1640-6. [PMID: 15732866 DOI: 10.1902/jop.2004.75.12.1640] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND The aim of the present study was 1) to evaluate the possible effects of therapeutic usage of omega-3 fatty acid on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), platelet activating factor (PAF), and leukotriene B4 (LTB4) in endotoxin-induced periodontitis in rats and 2) to investigate whether prophylactic usage provides any additional benefits to therapeutic doses of omega-3 fatty acid. METHODS Experimental periodontitis was induced by repeated injection of Escherichia coli lipopolysaccharide (LPS). Thirty-six adult male Sprague-Dawley rats were divided into four study groups: 1) saline controls; 2) LPS; 3) therapeutic omega-3 fatty acid (TO3); and 4) prophylactic plus therapeutic omega-3 fatty acid (P + TO3) groups. In TO3 group, omega-3 fatty acid was given for 15 days following induction of experimental periodontitis. In P + TO3 group, omega-3 fatty acid was started 15 days before baseline, and then periodontitis was induced at baseline and omega-3 fatty acid was continued for 15 days after baseline. On day 15 after baseline, all rats were anesthetized and sacrificed. PGE2, PGF2alpha, and LTB4 levels in gingival tissue samples were analyzed by enzyme immunoassay and PAF levels were analyzed by radioimmonoassay. Data were evaluated statistically by using parametric tests. RESULTS LPS injection resulted in significant amount of bone loss (P<0.05). Neither therapeutic nor prophylactic plus therapeutic administration of omega-3 fatty acid with the doses and duration of therapy used in the present study was effective in preventing endotoxin-induced alveolar bone loss. TO3 group exhibited significant decreases in the gingival tissue levels of PGE2, PGF2alpha, LTB4, and PAF compared to the LPS group (P<0.05). PGE2 and PGF2alpha levels in TO3 group were similar to those of the saline group (P>0.05), while LTB4 and PAF levels were statistically higher than the saline group (P<0.05). Prophylactic plus therapeutic usage of omega-3 fatty acid provided similar levels of all these mediators to those of the saline controls (P>0.05). CONCLUSIONS Therapeutic omega-3 fatty acid significantly reduced the gingival tissue levels of PGE2, PGF2alpha, LTB4, and PAF in experimental periodontitis. Furthermore, prophylactic usage of omega-3 fatty acid provided additional beneficial effects to the therapeutic administration by decreasing the gingival tissue levels of these mediators to levels of healthy tissue. These findings should be verified by longitudinal clinical trials investigating clinical and biochemical periodontal parameters to better define the possible role of omega-3 fatty acids in periodontal treatment.
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Affiliation(s)
- Saynur Vardar
- Ege University, School of Dentistry, Department of Periodontology, Izmir, Turkey.
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Nassar CA, Nassar PO, Nassar PM, Spolidorio LC. Selective cyclooxygenase-2 inhibition prevents bone resorption. Braz Oral Res 2005; 19:36-40. [PMID: 16229354 DOI: 10.1590/s1806-83242005000100007] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The aim of the present work was to evaluate the effect of a selective cyclooxygenase-2 (COX-2) inhibitor (meloxicam) on the alveolar bone loss progression in experimentally induced periodontitis. Forty (40) Wistar rats were separated into 8 experimental groups (n = 5). Cotton ligatures were placed at the gingival margin level of the lower right first molars of some rats. Four groups were treated for 5 or 15 days with an oral dose of 15 mg/kg of body weight/day of the selective COX-2 inhibitor. The other groups were used as positive control (sham) or negative control in each experimental period. Standardized digital radiographs were taken after sacrifice at 5 and 15 days to measure the amount of bone loss at the mesial root surface of the first molar tooth in each rat. The treatment with meloxicam did not induce weight alteration or other visible systemic manifestations. One way analysis of variance (ANOVA) indicated that groups treated with meloxicam, after 5 days, had significantly less alveolar bone loss (p < 0.05) when compared with control groups. On the other hand, no significant differences in bone loss were observed after 15 days of treatment with meloxicam. These data provide evidence that systemic therapy with meloxicam can modify the progression of experimentally induced periodontitis in rats during the initial experimental period.
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Affiliation(s)
- Carlos Augusto Nassar
- Department of Periodontology, School of Dentistry of Cascavel, State University of Paraná
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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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Deinzer R, Waschul B, Herforth A. Effects of experimental gingivitis on crevicular PGE2 in a split mouth trial. J Clin Periodontol 2004; 31:501-5. [PMID: 15191583 DOI: 10.1111/j.1600-051x.2004.00506.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVE The study aimed to analyse the effects of experimental gingivitis on crevicular prostaglandin E(2) (PGE(2)). An increase of PGE(2) was expected. METHODS Fourteen medical students refrained for 28 days from any oral hygiene procedures in two antagonistic quadrants while they maintained close to perfect oral hygiene in the remaining quadrants. Crevicular fluid samples were taken at baseline and at days 7, 14, 21 and 28 of experimental gingivitis both from quadrants with and without oral hygiene. PGE(2)-concentrations (ng/ml) and absolute levels (pg/sample) were analysed for quadrants with and without oral hygiene. RESULTS Comparison of quadrants with and without oral hygiene by repeated measures anova revealed no effects of experimental gingivitis both on crevicular PGE(2)-concentrations and absolute levels. CONCLUSION The study does not support the notion that experimental gingivitis induces an increase of crevicular PGE(2). The data are discussed in the context of other studies on PGE(2) concentrations in gingivitis. Close inspection of these studies reveals no clear evidence for an increase of local PGE(2) in gingivitis.
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Affiliation(s)
- Renate Deinzer
- Institute of Medical Psychology, University of Duesseldorf, Germany.
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Mulshine JL, Atkinson JC, Greer RO, Papadimitrakopoulou VA, Van Waes C, Rudy S, Martin JW, Steinberg SM, Liewehr DJ, Avis I, Linnoila RI, Hewitt S, Lippman SM, Frye R, Cavanaugh PF. Randomized, Double-Blind, Placebo-Controlled Phase IIB Trial of the Cyclooxygenase Inhibitor Ketorolac as an Oral Rinse in Oropharyngeal Leukoplakia. Clin Cancer Res 2004; 10:1565-73. [PMID: 15014005 DOI: 10.1158/1078-0432.ccr-1020-3] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE Nonselective cyclooxygenase (COX) inhibitors have been reported to decrease the frequency of upper aerodigestive cancers. Ketorolac tromethamine oral rinse has been shown to resolve another COX-dependent process, periodontal disease, without incurring gastrointestinal side effects. This trial evaluated if a topically delivered oral rinse containing ketorolac was as safe as and more effective than oral rinse alone in reducing the area of oral leukoplakia. EXPERIMENTAL DESIGN 57 patients were randomized (2:1 ratio) in a double-blind, placebo-controlled study of ketorolac (10 ml of a 0.1% ketorolac rinse solution; n = 38) or placebo (10 ml of rinse solution; n = 19) given twice daily for 30 s over 90 days. Primary end point was evaluated visually obtaining bidimensional measurement of the size of leukoplakia lesion(s) at entry and at 90 days. Secondary end point was histological assessment of the leukoplakia as sampled by serial punch biopsy and independently reviewed by three pathologists. RESULTS The patients included 67% males, 11% non-Caucasian, and 86% used tobacco with no significant differences between the two arms. Both rinses were well tolerated with good compliance, and there was no significant difference in adverse events (P = 0.27). Major response rate (complete response and partial response) was 30% for ketorolac and 32% for the placebo arm. There was no significant difference in change in histology between the two arms. CONCLUSION Local delivery of a COX-containing oral rinse was well tolerated but produced no significant reduction in the extent of leukoplakia compared with the placebo. However, the favorable response rate to placebo arm remains unexplained and additional investigation of the tissue penetration with ketorolac is warranted.
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Affiliation(s)
- James L Mulshine
- Intervention Section, Cell and Cancer Biology Branch, Department of Pathology and Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1906, 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: 147] [Impact Index Per Article: 7.0] [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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