Clinical, microbiological and oxidative stress evaluation of periodontitis patients treated with two regimens of systemic antibiotics, adjunctive to non-surgical therapy: A placebo-controlled randomized clinical trial

Boia,Simina; Boariu,Marius; Baderca,Flavia; Rusu,Darian; Muntean,Delia; Horhat,Florin; Boia,Eugen-Radu; Borza,Claudia; Anghel,Andrei; Stratul,Ştefan-Ioan

doi:10.3892/etm.2019.7856

Clinical, microbiological and oxidative stress evaluation of periodontitis patients treated with two regimens of systemic antibiotics, adjunctive to non-surgical therapy: A placebo-controlled randomized clinical trial

Authors:
- Simina Boia
- Marius Boariu
- Flavia Baderca
- Darian Rusu
- Delia Muntean
- Florin Horhat
- Eugen-Radu Boia
- Claudia Borza
- Andrei Anghel
- Ştefan-Ioan Stratul
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Affiliations: Department of Periodontology, Faculty of Dental Medicine, ‘Victor Babeş’ University of Medicine and Pharmacy, Timişoara 300041, Romania, Department of Endodontics, Faculty of Dental Medicine, ‘Victor Babeş’ University of Medicine and Pharmacy, Timişoara 300041, Romania, Department of Histology, Faculty of Medicine, ‘Victor Babeş’ University of Medicine and Pharmacy, Timişoara 300041, Romania, Department of Microbiology, Faculty of Medicine, ‘Victor Babeş’ University of Medicine and Pharmacy, Timişoara 300041, Romania, Department of ENT, Faculty of Medicine, ‘Victor Babeş’ University of Medicine and Pharmacy, Timişoara 300041, Romania, Department of Pathophysiology Faculty of Medicine, ‘Victor Babeş’ University of Medicine and Pharmacy, Timişoara 300041, Romania, Department of Biochemistry, Faculty of Medicine, ‘Victor Babeş’ University of Medicine and Pharmacy, Timişoara 300041, Romania
Published online on: August 5, 2019 https://doi.org/10.3892/etm.2019.7856
Pages: 5001-5015
Copyright: © Boia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Aim of research was to evaluate and compare the clinical and microbiological effects of two different regimens of amoxicillin (AMX) and metronidazole (MTZ) combined with non‑surgical periodontal therapy in patients with chronic periodontitis (CP), and identify antibiotic‑resistant bacteria and changes in oxidative stress (OS). Forty-six patients with generalized CP were randomly assigned to group A [scaling and root planing within 24 h (SRP) + placebo for 7 days), group B [SRP + AMX + MTZ, both 500 mg three times daily (TID), 3 days), and group C [SRP + AMX + MTZ, both 500 mg TID, 7 days). Periodontal pocket depth (PPD‑primary outcome), clinical attachment level (CAL), full‑mouth bleeding scores (FMBS), plaque scores (FMPS), blood and subgingival plaque were assessed at baseline and after three months. OS was evaluated via derivatives of reactive oxygen metabolites (d‑ROMs) and assessments of biological antioxidant potential (BAP). Bacterial profiling was performed by PCR. Antibiotic resistance was evaluated in cultures. PPD, CAL, number of sites with PPD ≥6 mm, their PPD, CAL and FMBS decreased (P<0.05) in all groups, as well as FMPS in groups A and B, and d‑ROMs in group C. There were significant differences among groups regarding decreases in the frequency of detection for Aa and Tf. For Aa, there were differences between groups A and C (P=0.048) and between groups B and C (P=0.048), but not between groups A and B; whereas for Tf, groups A and B were different from group C (P<0.001), but not from each other (P=0.920). No resistance to AMX was identified prior to treatment; two strains were resistant after treatment. Before treatment, 13 strains were resistant to MTZ, and 2 were resistant after. One strain in the same patient was sensitive prior to treatment, and later became resistant to both antibiotics. SRP with a 7‑day course of antibiotic therapy was more effective for improving clinical parameters, in decrease of detection of several periopathogens, and in improvement of OS when compared to a 3‑day regimen. Resistance was found in fewer strains after treatment than before.

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1	Egelberg J: Periodontics the Scientific Way, Synopses of Clinical Studies1. 3rd. Odonto Science; Malmo: pp. 121999
2	Cugini MA, Haffajee AD, Smith C, Kent RL Jr and Socransky SS: The effect of scaling and root planing on the clinical and microbiological parameters of periodontal diseases: 12-month results. J Clin Periodontol. 27:30–36. 2000. View Article : Google Scholar : PubMed/NCBI
3	Carvalho LH, D'Avila GB, Leão A, Haffajee AD, Socransky SS and Feres M: Scaling and root planing, systemic metronidazole and professional plaque removal in the treatment of chronic periodontitis in a Brazilian population. I. Clinical results. J Clin Periodontol. 31:1070–1076. 2004. View Article : Google Scholar : PubMed/NCBI
4	Cosgarea R, Juncar R, Heumann C, Tristiu R, Lascu L, Arweiler N, Stavropoulos A and Sculean A: Non-surgical periodontal treatment in conjunction with 3 or 7 days systemic administration of amoxicillin and metronidazole in severe chronic periodontitis patients. A placebo-controlled randomized clinical study. J Clin Periodontol. 43:767–777. 2016. View Article : Google Scholar : PubMed/NCBI
5	Renvert S, Wikström M, Dahlén G, Slots J and Egelberg J: Effect of root debridement on the elimination of Actinobacillus actinomycetemcomitans and Bacteroides gingivalis from periodontal pockets. J Clin Periodontol. 17:345–350. 1990. View Article : Google Scholar : PubMed/NCBI
6	Mombelli A, Gmür R, Gobbi C and Lang NP: Actinobacillus actinomycetemcomitans in adult periodontitis. I. Topographic distribution before and after treatment. J Periodontol. 65:820–826. 1994. View Article : Google Scholar : PubMed/NCBI
7	Marsh PD: Dental plaque: Biological significance of a biofilm and community life-style. J Clin Periodontol. 32 (Suppl 6):7–15. 2005. View Article : Google Scholar : PubMed/NCBI
8	van Winkelhoff AJ, Rodenburg JP, Goené RJ, Abbas F, Winkel EG and de Graaff J: Metronidazole plus amoxycillin in the treatment of Actinobacillus actinomycetemcomitans associated periodontitis. J Clin Periodontol. 16:128–131. 1989. View Article : Google Scholar : PubMed/NCBI
9	Pavicić MJ, van Winkelhoff AJ, Douqué NH, Steures RW and de Graaff J: Microbiological and clinical effects of metronidazole and amoxicillin in Actinobacillus actinomycetemcomitans-associated periodontitis. A 2-year evaluation. J Clin Periodontol. 21:107–112. 1994. View Article : Google Scholar : PubMed/NCBI
10	Flemmig TF, Milián E, Karch H and Klaiber B: Differential clinical treatment outcome after systemic metronidazole and amoxicillin in patients harboring Actinobacillus actinomycetemcomitans and/or Porphyromonas gingivalis. J Clin Periodontol. 25:380–387. 1998. View Article : Google Scholar : PubMed/NCBI
11	Goutoudi P, Diza E and Arvanitidou M: Effect of periodontal therapy on crevicular fluid interleukin-1beta and interleukin-10 levels in chronic periodontitis. J Dent. 32:511–520. 2004. View Article : Google Scholar : PubMed/NCBI
12	Guerrero A, Griffiths GS, Nibali L, Suvan J, Moles DR, Laurell L and Tonetti MS: Adjunctive benefits of systemic amoxicillin and metronidazole in non-surgical treatment of generalized aggressive periodontitis: A randomized placebo-controlled clinical trial. J Clin Periodontol. 32:1096–1107. 2005. View Article : Google Scholar : PubMed/NCBI
13	Ehmke B, Moter A, Beikler T, Milian E and Flemmig TF: Adjunctive antimicrobial therapy of periodontitis: Long-term effects on disease progression and oral colonization. J Periodontol. 76:749–759. 2005. View Article : Google Scholar : PubMed/NCBI
14	Cionca N, Giannopoulou C, Ugolotti G and Mombelli A: Amoxicillin and metronidazole as an adjunct to full-mouth scaling and root planing of chronic periodontitis. J Periodontol. 80:364–371. 2009. View Article : Google Scholar : PubMed/NCBI
15	Cionca N, Giannopoulou C, Ugolotti G and Mombelli A: Microbiologic testing and outcomes of full-mouth scaling and root planing with or without amoxicillin/metronidazole in chronic periodontitis. J Periodontol. 81:15–23. 2010. View Article : Google Scholar : PubMed/NCBI
16	Ribeiro EP, Bittencourt S, Zanin IC, Bovi Ambrosano GM, Sallum EA, Nociti FH Jr, Gonçalves RB and Casati MZ: Full-mouth ultrasonic debridement associated with amoxicillin and metronidazole in the treatment of severe chronic periodontitis. J Periodontol. 80:1254–1264. 2009. View Article : Google Scholar : PubMed/NCBI
17	Yek EC, Cintan S, Topcuoglu N, Kulekci G, Issever H and Kantarci A: Efficacy of amoxicillin and metronidazole combination for the management of generalized aggressive periodontitis. J Periodontol. 81:964–974. 2010. View Article : Google Scholar : PubMed/NCBI
18	Rodrigues AS, Lourenção DS, Lima Neto LG, Pannuti CM, Hirata RD, Hirata MH, Lotufo RF and De Micheli G: Clinical and microbiologic evaluation, by real-time polymerase chain reaction, of non-surgical treatment of aggressive periodontitis associated with amoxicillin and metronidazole. J Periodontol. 83:744–752. 2012. View Article : Google Scholar : PubMed/NCBI
19	Rooney J, Wade WG, Sprague SV, Newcombe RG and Addy M: Adjunctive effects to non-surgical periodontal therapy of systemic metronidazole and amoxycillin alone and combined. A placebo controlled study. J Clin Periodontol. 29:342–350. 2002. View Article : Google Scholar : PubMed/NCBI
20	Matarazzo F, Figueiredo LC, Cruz SE, Faveri M and Feres M: Clinical and microbiological benefits of systemic metronidazole and amoxicillin in the treatment of smokers with chronic periodontitis: A randomized placebo-controlled study. J Clin Periodontol. 35:885–896. 2008. View Article : Google Scholar : PubMed/NCBI
21	Mestnik MJ, Feres M, Figueiredo LC, Duarte PM, Lira EA and Faveri M: Short-term benefits of the adjunctive use of metronidazole plus amoxicillin in the microbial profile and in the clinical parameters of subjects with generalized aggressive periodontitis. J Clin Periodontol. 37:353–365. 2010. View Article : Google Scholar : PubMed/NCBI
22	Mestnik MJ, Feres M, Figueiredo LC, Soares G, Teles RP, Fermiano D, Duarte PM and Faveri M: The effects of adjunctive metronidazole plus amoxicillin in the treatment of generalized aggressive periodontitis: A 1-year double-blinded, placebo-controlled, randomized clinical trial. J Clin Periodontol. 39:955–961. 2012. View Article : Google Scholar : PubMed/NCBI
23	Heller D, Varela VM, Silva-Senem MX, Torres MC, Feres-Filho EJ and Colombo AP: Impact of systemic antimicrobials combined with anti-infective mechanical debridement on the microbiota of generalized aggressive periodontitis: A 6-month RCT. J Clin Periodontol. 38:355–364. 2011. View Article : Google Scholar : PubMed/NCBI
24	Silva MP, Feres M, Sirotto TA, Soares GM, Mendes JA, Faveri M and Figueiredo LC: Clinical and microbiological benefits of metronidazole alone or with amoxicillin as adjuncts in the treatment of chronic periodontitis: A randomized placebo-controlled clinical trial. J Clin Periodontol. 38:828–837. 2011. View Article : Google Scholar : PubMed/NCBI
25	Feres M, Soares GM, Mendes JA, Silva MP, Faveri M, Teles R, Socransky SS and Figueiredo LC: Metronidazole alone or with amoxicillin as adjuncts to non-surgical treatment of chronic periodontitis: A 1-year double-blinded, placebo-controlled, randomized clinical trial. J Clin Periodontol. 39:1149–1158. 2012. View Article : Google Scholar : PubMed/NCBI
26	Griffiths GS, Ayob R, Guerrero A, Nibali L, Suvan J, Moles DR and Tonetti MS: Amoxicillin and metronidazole as an adjunctive treatment in generalized aggressive periodontitis at initial therapy or re-treatment: A randomized controlled clinical trial. J Clin Periodontol. 38:43–49. 2011. View Article : Google Scholar : PubMed/NCBI
27	Jorgensen MG and Slots J: Responsible use of antimicrobials in periodontics. J Calif Dent Assoc. 28:185–193. 2000.PubMed/NCBI
28	Newman MG, Tkei HH, Klokkevold PR and Carranza FA: Newman and Carranza's Clinical Periodontology.1. 13th. Elsevier; Amsterdam: 2019
29	Vogelman B and Craig WA: Kinetics of antimicrobial activity. J Pediatr. 108:835–840. 1986. View Article : Google Scholar : PubMed/NCBI
30	Cosgarea R, Heumann C, Juncar R, Tristiu R, Lascu L, Salvi GE, Arweiler NB and Sculean A: One year results of a randomized controlled clinical study evaluating the effects of non-surgical periodontal therapy of chronic periodontitis in conjunction with three or seven days systemic administration of amoxicillin/metronidazole. PLoS One. 12:e01795922017. View Article : Google Scholar : PubMed/NCBI
31	Laxminarayan R, Duse A, Wattal C, Zaidi AK, Wertheim HF, Sumpradit N, Vlieghe E, Hara GL, Gould IM, Goossens H, et al: Antibiotic resistance-the need for global solutions. Lancet Infect Dis. 13:1057–1098. 2013. View Article : Google Scholar : PubMed/NCBI
32	Mah MW and Memish ZA: Antibiotic resistance. An impending crisis. Saudi Med J. 21:1125–1129. 2000.PubMed/NCBI
33	Rams TE, Degener JE and van Winkelhoff AJ: Antibiotic resistance in human chronic periodontitis microbiota. J Periodontol. 85:160–169. 2014. View Article : Google Scholar : PubMed/NCBI
34	van Winkelhoff AJ, Tijhof CJ and de Graaff J: Microbiological and clinical results of metronidazole plus amoxicillin therapy in Actinobacillus actinomycetemcomitans-associated periodontitis. J Periodontol. 63:52–57. 1992. View Article : Google Scholar : PubMed/NCBI
35	van Winkelhoff AJ, Herrera D, Oteo A and Sanz M: Antimicrobial profiles of periodontal pathogens isolated from periodontitis patients in The Netherlands and Spain. J Clin Periodontol. 32:893–898. 2005. View Article : Google Scholar : PubMed/NCBI
36	Feres M, Haffajee AD, Allard K, Som S, Goodson JM and Socransky SS: Antibiotic resistance of subgingival species during and after antibiotic therapy. J Clin Periodontol. 29:724–735. 2002. View Article : Google Scholar : PubMed/NCBI
37	Maestre JR, Bascones A, Sánchez P, Matesanz P, Aguilar L, Giménez MJ, Pérez-Balcabao I, Granizo JJ and Prieto J: Odontogenic bacteria in periodontal disease and resistance patterns to common antibiotics used as treatment and prophylaxis in odontology in Spain. Rev Esp Quimioter. 20:61–67. 2007.PubMed/NCBI
38	Lakhssassi N, Elhajoui N, Lodter JP, Pineill JL and Sixou M: Antimicrobial susceptibility variation of 50 anaerobic periopathogens in aggressive periodontitis: An interindividual variability study. Oral Microbiol Immunol. 20:244–252. 2005. View Article : Google Scholar : PubMed/NCBI
39	Dehelean CA, Soica C, Pinzaru I, Coricovac D, Danciu C, Pavel I, Borcan F, Spandidos DA, Tsatsakis AM and Baderca F: Sex differences and pathology status correlated to the toxicity of some common carcinogens in experimental skin carcinoma. Food Chem Toxicol. 95:149–158. 2016. View Article : Google Scholar : PubMed/NCBI
40	Pricop R, Cristea VC, Gheorghe I, Tatu AL, Mihaescu G and Chifiriuc MC: Matrix-assisted laser desorption/ionization time-of-flight mas spectrometry (MALDI-TOF MS) reveals the anaerobic Slakia exigua as unique etiology of a dental abscess. Biointerface Res Appl Chem. 7:1995–1997. 2017.
41	Oktay S, Chukkapalli SS, Rivera-Kweh MF, Velsko IM, Holliday LS and Kesavalu L: Periodontitis in rats induces systemic oxidative stress that is controlled by bone-targeted antiresorptives. J Periodontol. 86:137–145. 2015. View Article : Google Scholar : PubMed/NCBI
42	Căruntu C, Boda D, Musat S, Căruntu A and Mandache E: Stress-induced mast cell activation in glabrous and hairy skin. Mediators Inflamm. 2014:1059502014. View Article : Google Scholar : PubMed/NCBI
43	Dahiya P, Kamal R, Gupta R, Bhardwaj R, Chaudhary K and Kaur S: Reactive oxygen species in periodontitis. J Indian Soc Periodontol. 17:411–416. 2013. View Article : Google Scholar : PubMed/NCBI
44	Robinson JM: Reactive oxygen species in phagocytic leukocytes. Histochem Cell Biol. 130:281–297. 2008. View Article : Google Scholar : PubMed/NCBI
45	Tóthová L and Celec P: Oxidative stress and antioxidants in the diagnosis and therapy of periodontitis. Front Physiol. 8:10552017. View Article : Google Scholar : PubMed/NCBI
46	Tsai CC, Chen HS, Chen SL, Ho YP, Ho KY, Wu YM and Hung CC: Lipid peroxidation: A possible role in the induction and progression of chronic periodontitis. J Periodontal Res. 40:378–384. 2005. View Article : Google Scholar : PubMed/NCBI
47	Konopka T, Król K, Kopeć W and Gerber H: Total antioxidant status and 8-hydroxy-2-deoxyguanosine levels in gingival and peripheral blood of periodontitis patients. Arch Immunol Ther Exp (Warsz). 55:417–422. 2007. View Article : Google Scholar : PubMed/NCBI
48	Akalin FA, Baltacioğlu E, Alver A and Karabulut E: Lipid peroxidation levels and total oxidant status in serum, saliva and gingival crevicular fluid in patients with chronic periodontitis. J Clin Periodontol. 34:558–565. 2007. View Article : Google Scholar : PubMed/NCBI
49	Chapple IL, Brock GR, Milward MR, Ling N and Matthews JB: Compromised GCF total antioxidant capacity in periodontitis: Cause or effect? J Clin Periodontol. 34:103–110. 2007. View Article : Google Scholar : PubMed/NCBI
50	Armitage GC: Development of a classification system for periodontal diseases and conditions. Ann Periodontol. 4:1–6. 1999. View Article : Google Scholar : PubMed/NCBI
51	Tonetti MS, Pini-Prato G and Cortellini P: Effect of cigarette smoking on periodontal healing following GTR in infrabony defects. A preliminary retrospective study. J Clin Periodontol. 22:229–234. 1995. View Article : Google Scholar : PubMed/NCBI
52	Miller PD Jr: A classification of marginal tissue recession. Int J Periodontics Restorative Dent. 5:8–13. 1985.PubMed/NCBI
53	Hamp SE, Nyman S and Lindhe J: Periodontal treatment of multirooted teeth. Results after 5 years. J Clin Periodontol. 2:126–135. 1975. View Article : Google Scholar : PubMed/NCBI
54	Quirynen M, Bollen CML, Vandekerckhove BN, Dekeyser C, Papaioannou W and Eyssen H: Full- vs. partial-mouth disinfection in the treatment of periodontal infections: Short-term clinical and microbiological observations. J Dent Res. 74:1459–1467. 1995. View Article : Google Scholar : PubMed/NCBI
55	Slots J: Selective medium for isolation of Actinobacillus actinomycetemcomitans. J Clin Microbiol. 15:606–609. 1982.PubMed/NCBI
56	Tatu AL, Merezeanu N, Pântea O, Gheorghe I, Popa M, Banu O, Cristea VC, Chifiriuc MC, Lazăr V and Marutescu L: Resistance features of Pseudomonas aeruginosa strains isolated from patients with infectious complications of cardiovascular surgery. Biointerface Res Appl Chem. 7:2004–2008. 2017.
57	Gheorghe I, Tatu AL, Lupu I, Thamer O, Cotar AI, Pircalabioru GG, Popa M, Cristea VC, Lazar V and Chifiriuc MC: Molecular characterization of virulence and resistance features in Staphylococcus aureus clinical strains isolated from cutaneous lesions in patients with drug adverse reactions. Rom Biotechnol Lett. 22:12321–12327. 2017.
58	R Core Team, . A language and Environment for Statistical ComputingFoundation for Statistical Computing; Vienna: pp. 2012017
59	Gamer M, Lemon J, Fellows I and Singh P: irr: Various Coefficients of Interrater Reliability and Agreement. R package version 0.84.1. 2019.
60	Hettmansperger TP and McKean JW: Robust nonparametric statistical methods.1. 2nd. Chapman & Hall; Boca Raton, FL: 2011
61	Kloke J and McKean J: Npsm R package nonparametric statistical methods using RCRC Press; Boca Raton, FL: pp. 2872019
62	Winkel EG, Van Winkelhoff AJ, Timmerman MF, Van der Velden U and Van der Weijden GA: Amoxicillin plus metronidazole in the treatment of adult periodontitis patients. A double-blind placebo-controlled study. J Clin Periodontol. 28:296–305. 2001. View Article : Google Scholar : PubMed/NCBI
63	Heta S and Robo I: The side effects of the most commonly used group of antibiotics in periodontal treatments. Med Sci (Basel). 6:E62018.PubMed/NCBI
64	Rodrigues RM, Gonçalves C, Souto R, Feres-Filho EJ, Uzeda M and Colombo AP: Antibiotic resistance profile of the subgingival microbiota following systemic or local tetracycline therapy. J Clin Periodontol. 31:420–427. 2004. View Article : Google Scholar : PubMed/NCBI
65	Fiehn NE and Westergaard J: Doxycycline-resistant bacteria in periodontally diseased individuals after systemic doxycycline therapy and in healthy individuals. Oral Microbiol Immunol. 5:219–222. 1990. View Article : Google Scholar : PubMed/NCBI
66	Feres M, Haffajee AD, Goncalves C, Allard KA, Som S, Smith C, Goodson JM and Socransky SS: Systemic doxycycline administration in the treatment of periodontal infections (II). Effect on antibiotic resistance of subgingival species. J Clin Periodontol. 26:784–792. 1999. View Article : Google Scholar : PubMed/NCBI
67	Walker CB: The acquisition of antibiotic resistance in the periodontal microflora. Periodontol 2000. 10:79–88. 1996. View Article : Google Scholar : PubMed/NCBI
68	Herrera D, Roldán S, O'Connor A and Sanz M: The periodontal abscess (II). Short-term clinical and microbiological efficacy of 2 systemic antibiotic regimes. J Clin Periodontol. 27:395–404. 2000. View Article : Google Scholar : PubMed/NCBI
69	Ardila CM, Granada MI and Guzmán IC: Antibiotic resistance of subgingival species in chronic periodontitis patients. J Periodontal Res. 45:557–563. 2010.PubMed/NCBI
70	Boda D, Negrei C, Nicolescu F and Balalau C: Assessment of some oxidative stress parameters in methotrexate treated psoriasis patients. Farmacia. 62:704–710. 2014.
71	Tamaki N, Tomofuji T, Ekuni D, Yamanaka R, Yamamoto T and Morita M: Short-term effects of non-surgical periodontal treatment on plasma level of reactive oxygen metabolites in patients with chronic periodontitis. J Periodontol. 80:901–906. 2009. View Article : Google Scholar : PubMed/NCBI
72	Rahman K: Studies on free radicals, antioxidants, and co-factors. Clin Interv Aging. 2:219–236. 2007.PubMed/NCBI
73	Nakayama K, Terawaki H, Nakayama M, Iwabuchi M, Sato T and Ito S: Reduction of serum antioxidative capacity during hemodialysis. Clin Exp Nephrol. 11:218–224. 2007. View Article : Google Scholar : PubMed/NCBI
74	Kim JH, Baik HW, Yoon YS, Joung HJ, Park JS, Park SJ, Jang EJ, Park SW, Kim SJ, Kim MJ, et al: Measurement of antioxidant capacity using the biological antioxidant potential test and its role as a predictive marker of metabolic syndrome. Korean J Intern Med (Korean Assoc Intern Med). 29:31–39. 2014.
75	Tamaki N, Tomofuji T, Maruyama T, Ekuni D, Yamanaka R, Takeuchi N and Yamamoto T: Relationship between periodontal condition and plasma reactive oxygen metabolites in patients in the maintenance phase of periodontal treatment. J Periodontol. 79:2136–2142. 2008. View Article : Google Scholar : PubMed/NCBI
76	Machida T, Tomofuji T, Ekuni D, Yamane M, Yoneda T, Kawabata Y, Kataoka K, Tamaki N and Morita M: Longitudinal relationship between plasma reactive oxygen metabolites and periodontal condition in the maintenance phase of periodontal treatment. Dis Markers. 2014:4892922014. View Article : Google Scholar : PubMed/NCBI
77	D'Aiuto F, Nibali L, Parkar M, Patel K, Suvan J and Donos N: Oxidative stress, systemic inflammation, and severe periodontitis. J Dent Res. 89:1241–1246. 2010. View Article : Google Scholar : PubMed/NCBI
78	Boda D: Cellomics as integrative omics for cancer. Curr Proteomics. 10:237–245. 2013. View Article : Google Scholar
79	Gupta A, Govila V and Saini A: Proteomics - The research frontier in periodontics. J Oral Biol Craniofac Res. 5:46–52. 2015. View Article : Google Scholar : PubMed/NCBI
80	Calenic B, Greabu M, Caruntu C, Nicolescu MI, Moraru L, Surdu-Bob CC, Badulescu M, Anghel A, Logofatu C and Boda D: Oral keratinocyte stem cells behavior on diamond like carbon films. Rom Biotechnol Lett. 21:11914–11922. 2016.