|Year : 2022 | Volume
| Issue : 3 | Page : 579-583
Evaluation of efficacy of hi-ora mouthrinse as against 0.12% chlorhexidine in treatment of patients with chronic gingivitis: A randomized-controlled trial
Anitha Akkaloori1, Maher Al Shayeb2, Praveena Raman3, Kurian Punnoose4, Prajna Pattanaik5, Reghunathan S Preethanath6, J Suresh Babu7, C Swarnalatha7, Abhishek Singh Nayyar8
1 Department of Public Health Dentistry, Government Dental College and Hospital, Hyderabad, Telangana, India
2 Department of Clinical Sciences, College of Dentistry, Center for Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
3 Department of Oral Medicine and Radiology, Sathyabama Dental College and Hospital, Chennai, Tamil Nadu, India
4 Department of Oral and Maxillofacial Surgery, College of Dentistry, University of Ha'il, Ha'il, Saudi Arabia
5 Department of Conservative Dentistry and Endodontics, Institute of Dental Sciences, Bhubaneswar, Odisha, India
6 Department of Preventive Dental Sciences, College of Dentistry, Jazan University, Jazan, Saudi Arabia
7 Department of Preventive Dental Sciences, Division of Periodontology, College of Dentistry, University of Ha'il, Ha'il, Saudi Arabia
8 Department of Oral Medicine and Radiology, Saraswati Dhanwantari Dental College and Hospital and Post Graduate Research Institute, Parbhani, Maharashtra, India
|Date of Submission||15-Aug-2022|
|Date of Decision||25-Aug-2022|
|Date of Acceptance||29-Aug-2022|
|Date of Web Publication||2-Nov-2022|
Dr. Anitha Akkaloori
Department of Public Health Dentistry, Government Dental College and Hospital, Hyderabad, Telangana
Source of Support: None, Conflict of Interest: None
Background: The present study was planned to compare the efficacy of Hi-Ora mouthrinse as against 0.12% chlorhexidine (CHX) in treatment of patients with chronic gingivitis. Materials and Methods: The present study was designed as a randomized controlled trial including 90 patients with chronic gingivitis who were divided into three groups including Group A in which 0.12% CHX was prescribed, Group B in which patients were prescribed Hi-Ora, and Group C in which normal saline was prescribed after oral prophylaxis while the mean gingival index (GI) and plaque index (PI) scores were recorded after 1 week. Inter-group comparisons between different groups were done with the help of Independent t-test and Tukey's post hoc test while P < 0.05 was considered statistically significant. Results: In the present study, the mean GI score (postintervention) was found to be 0.71 ± 0.27 in CHX, 0.68 ± 0.17 in Hi-Ora, and 1.59 ± 0.55 in the normal saline group with the results being statistically significant (P < 0.0001). Similarly, the mean PI score in the present study was found to be 0.81 ± 0.34 in the CHX group with the corresponding values being 0.79 ± 0.28 in Hi-Ora and 1.86 ± 0.61 in the normal saline group with statistically significant results (P < 0.0001). Conclusions: The results of the present study suggested Hi-Ora to be equally efficacious as 0.12% CHX in reducing the mean GI and PI scores in patients with chronic gingivitis.
Keywords: Chlorhexidine, gingivitis, Hi-Ora, normal saline, randomized-controlled trial
|How to cite this article:|
Akkaloori A, Al Shayeb M, Raman P, Punnoose K, Pattanaik P, Preethanath RS, Babu J S, Swarnalatha C, Nayyar AS. Evaluation of efficacy of hi-ora mouthrinse as against 0.12% chlorhexidine in treatment of patients with chronic gingivitis: A randomized-controlled trial. J Datta Meghe Inst Med Sci Univ 2022;17:579-83
|How to cite this URL:|
Akkaloori A, Al Shayeb M, Raman P, Punnoose K, Pattanaik P, Preethanath RS, Babu J S, Swarnalatha C, Nayyar AS. Evaluation of efficacy of hi-ora mouthrinse as against 0.12% chlorhexidine in treatment of patients with chronic gingivitis: A randomized-controlled trial. J Datta Meghe Inst Med Sci Univ [serial online] 2022 [cited 2023 Feb 1];17:579-83. Available from: http://www.journaldmims.com/text.asp?2022/17/3/579/360215
| Introduction|| |
Plaque is considered to be the prime etiological factor in gingival inflammation while several factors have been shown to modulate clinical expression of gingival inflammation in response to plaque accumulation. The common features of plaque-induced gingivitis include clinical signs and symptoms of inflammation confined to free marginal and attached gingiva that do not extend to the other periodontal tissues, namely, cementum, alveolar bone and periodontal ligament, reversibility of inflammatory changes on the removal of the plaque biofilm, presence of high bacterial plaque burden needed to initiate inflammation and stable attachment levels on periodontium which may or may not have experienced loss of attachment or, alveolar bone., The diagnostic criteria for gingivitis are based largely on clinical features while radiographs do not have a role to define gingivitis since the condition is confined only to gingival soft tissues. Clinical signs of gingivitis include swelling with loss of knife-edged gingival margins and blunting of papillae, erythema, and bleeding and discomfort on probing or, a tendency for spontaneous bleeds on even slightest of the provocations based on the severity of inflammation. Under the classification system of the American Academy of Periodontology (AAP), gingivitis is defined as an inflammatory condition which is confined to the tissues of marginal gingiva while if untreated, it can involve periodontal tissues resulting in eventual tooth loss. Although there are no objective clinical criteria for defining the severity of gingivitis, the gingival index (GI) by Löe can be used to describe the extent of gingivitis (mild, moderate, and severe) based on clinical signs and symptoms.
Chlorhexidine (CHX) gluconate, developed in the 1950s, is still considered the gold standard and one of the most effective anti-plaque agents available with a broad spectrum antimicrobial activity, although, long-term usage of the same is limited by its disagreeable taste and tendency to lead to staining of the teeth. CHX is a cationic bis-biguanide which gets adsorbed to a variety of negatively charged sites in the oral cavity including mucous membranes, salivary pellicle, and plaque biofilms. Moreover, CHX has a distinct ability to be retained on to the tissues after adsorption for several hours aiding in preventing plaque re-growth and bacterial colonization. There is no dearth of studies that have proven the efficacy of CHX for its potent and broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria, and even, fungi, and certain viruses. Commercially available mouthrinses containing CHX, though have been reported with certain disadvantages with altered/metallic taste, irritation of soft tissues, and staining of teeth over a period of time as the major complaints in such patients.,
Recently, there have been few studies which have validated herbal mouthrinses as an effective substitute to CHX. In a similar context, Hi-Ora mouthrinse used in the present study has been reported with proven anti-plaque and antimicrobial properties. It has active herbal ingredients in the form of Miswak (Salvadora persica), Bibhitaka (Terminalia bellerica), Gandha Purataila, and Nagavalli (Piper betle) which are proven to have significant anti-plaque, antimicrobial, antiseptic, and analgesic properties. Furthermore, the alkaloid present in Miswak (S. Persica), Salvadorine, yields trimethylamine on hydrolytic cleavage exerting bactericidal effect while simultaneously having a stimulatory action on the gingiva. Tannins present in Miswak inhibit the action of enzyme glucosyltransferase reducing plaque build-up while sulfur compounds have an independent antibacterial effect. The silica present in Miswak, also, acts as a mild abrasive and remove stains on teeth. The present study was planned to compare the efficacy of Hi-Ora mouthrinse as against 0.12% CHX in the treatment of patients with chronic gingivitis.
| Materials and Methods|| |
Setting and design
The present study was designed as a randomized-controlled trial in the department of periodontology over a period of 1 year to evaluate the anti-plaque efficacy of Hi-Ora mouthrinse as against 0.12% CHX in patients with chronic gingivitis. Each step in the present trial was followed as per the Consolidated Standards of Reporting Trials 2010 guidelines, while before commencement, the study protocol was submitted for approval and ethical clearance was obtained from the Institutional Research and Ethics Committee through letter approval no. SIDS/IEC/07-377-2021. Furthermore, the patients who fulfilled the inclusion criteria were explained in detail about the research protocol and a written informed consent was obtained from them before their inclusion in the study.
Sample size estimation
The formula used for sample size estimation was as follows:
Standard deviation in the 1st Group S1 = 0.2198
Standard deviation in the 2nd Group S2 = 0.1987
Mean difference between 1st and 2nd sample = 0.1644
Effect size = 0.785663082437276
Alpha Error (%) = 5
Power (%) = 85
Sided = 2
Number needed (n) = 30 in each group to achieve 5% alpha error and 85% power.
The present study included 90 patients diagnosed with mild-to-moderate gingivitis in an age range of 20–45 years. The patients were diagnosed with gingivitis on the basis of established clinical criteria of change in color, contour, consistency, texture, size, and position of gingiva in addition to a tendency for bleeding on probing and/or, spontaneous bleeds with bleeding gums, metallic/altered taste, pain/soreness, halitosis, difficulty in eating, appearance of swollen red gums, and reduced oral health-related quality of life as the major complaints of the patients.,, The selected patients were allotted to the specified groups based on a simple randomization technique while patients with minimum of 10 teeth in each arch were included in this study. The patients who were diagnosed with any stage or, grade of periodontitis (according to the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions co-presented by the AAP and the European Federation of Periodontology), patients who presented with known hypersensitivity to mouthrinses, patients with systemic diseases and pregnant and lactating females were excluded from the study. The patients who were unwilling to participate in the study or, expressed their inability to complete the treatment protocol were, also, excluded.
The selected patients were divided into three groups with 30 patients in each group using simple randomization process including Group A in which 0.12% CHX (Hexidine® 60 ml, ICPA Health Products Ltd., Mumbai, India) was prescribed, Group B in which patients were prescribed Hi-Ora (Himalaya Drug Company, Bengaluru, India) and Group C in which normal saline was prescribed (as control) after oral prophylaxis. Hi-Ora mouthrinse (Himalaya Drug Company, Bengaluru, India) consisted of the extracts of Pilu (S. persica) 5 mg, Bibhitaka (T. bellerica) 10 mg, Nagavalli (P. betle) 10 mg, essential oils, namely, Gandhapura taila (Gaultheria fragrantissima) 1.2 mg, Ela (Elettaria cardamomum) 0.2 mg, flavoring agents, Peppermint satva (Mentha) 1.6 mg, and Yavani satva (Trachyspermum ammi) 0.4 mg in 30 ml w/v. The mean GI Loe and Silness and plaque index (PI) Silness and Loe scores were recorded after 1 week while postprocedural instructions included brushing twice a day with a soft brush with the prescribed rinse to be used after brushing postmeals., The subjects were advised to swish the prescribed mouthrinse (10 ml twice a day for 1 week) around in the mouth for a duration of 30 s and then, spit it out. The subjects were, also, advised to use the mouthrinse in the prescribed strength and not to mix water before using. There were no drop-outs reported in the study while the patients complied with the instructions given as assessed on re-call visit of patients.
For the purpose of scoring in case of GI, the gingival tissues surrounding each tooth were divided into four main areas including the disto-labial, labial, mesio-labial, and lingual margins of gingiva while the teeth and associated soft tissues were lightly air dried and then, wiped with cotton rolls before assessment. For the purpose of scoring for the PI, an explorer was passed across the tooth surface in the cervical third and near the entrance to gingival sulcus while findings were recorded. Furthermore, during the assessment, the examination for the PI scores was preceded by examination for the GI scores since manipulation of gingival tissues, in case of inflammation, led to bleeding on provocation.
The mean GI and PI scores were recorded by single observer who was a periodontist and blinded for the groups to avoid recording bias.
Statistical analysis used
The data were analyzed using SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). Independent t-test was used to assess whether the means of two groups were statistically different from one other while Tukey's post hoc test, also, known as Tukey's Honest Significant Difference test was used to assess the significance of differences between different pairs of group means P < 0.05 was considered statistically significant.
| Results|| |
The present study was designed as a randomized-controlled trial including 90 patients with chronic gingivitis in an age range of 20–45 years divided into three groups with 30 patients in each group using a simple randomization process including Group A in which 0.12% CHX was prescribed, Group B in which patients were prescribed Hi-Ora and Group C in which normal saline was prescribed (as control) after oral prophylaxis. In addition, there were no dropouts reported in the study. [Table 1] reveals the comparison of the mean GI scores in the groups using Independent t-test wherein the mean GI score (postintervention) was found to be 0.71 ± 0.27 in CHX, 0.68 ± 0.17 in Hi-Ora, and 1.59 ± 0.55 in the normal saline group with the results being statistically significant (P < 0.0001) [Table 1]. Likewise, [Table 2] reveals the comparison of the mean PI scores in the groups with the mean PI score in the CHX group being 0.81 ± 0.34 with the corresponding values being 0.79 ± 0.28 in Hi-Ora and 1.86 ± 0.61 in the normal saline group with statistically significant results (P < 0.0001) [Table 2]. On inter-group comparisons using Tukey's post hoc test, the results were found to be statistically significant when compared between CHX and normal saline and Hi-Ora and normal saline groups (P < 0.0001), though insignificant when compared between CHX and Hi-Ora for both GI (P = 0.886) and PI (P = 0.928) scores [Table 3].
|Table 1: Comparison of mean gingival index scores in groups using Independent t-test|
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|Table 2: Comparison of mean plaque index scores in groups using Independent t-test|
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|Table 3: Inter-group comparisons of mean gingival index and plaque index scores in groups using Tukey's posthoc test|
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| Discussion|| |
In the present study, the mean GI score (postintervention) was found to be 0.71 ± 0.27 in CHX, 0.68 ± 0.17 in Hi-Ora, and 1.59 ± 0.55 in the normal saline group with the results being statistically significant (P < 0.0001). Similarly, the mean PI score in the present study was found to be 0.81 ± 0.34 in the CHX group with the corresponding values being 0.79 ± 0.28 in Hi-Ora and 1.86 ± 0.61 in the normal saline group with statistically significant results (P < 0.0001). The results of the present study, thus, suggested Hi-Ora to be the most effective rinse in reducing the mean GI and PI scores among all three groups. Similar results were obtained in the study conducted by Jaidka et al. who observed the maximum anti-plaque, anti-gingivitis, and antibacterial effects in case of Hi-Ora group while the minimum effect in case of CHX group in contradiction to the previous studies which indicated CHX to be the gold standard and one of the most effective chemical anti-plaque agents.
The results of the present study were, also, found to be in accordance with the findings of the study conducted by Asiri et al. who observed a significant reduction in the GI and PI scores in both the groups using Hi-Ora and CHX concluding with the possibility of herbal mouthrinses to be used as an efficient replacement for CHX in the pretext of the inherent adverse effects seen with long-term usage of CHX. Similar results were obtained in the studies conducted by Bhat et al, Shetty et al and Gupta et al who observed no significant difference in the antimicrobial properties of herbal mouthrinses and CHX concluding both to be equally effective in inhibiting microbial growth. Also, there were fewer adverse effects observed in case of herbal mouthrinse group in these studies. Amongst these, Hi-Ora was used as herbal mouthrinse in the studies conducted by Bhat et al and Shetty et al while the herbal mouthrinse used in the study conducted by Gupta et al was a combination of 50% conc. of T. chebula and remaining 50% Cinnamon extract. Furthermore, CHX was reported to lead to potential side effects which limited its acceptability as against the herbal mouthrinse.
Pathan et al., also, found no statistically significant difference between Hi-Ora and CHX groups in their study when their effect was observed on select organisms in the in vitro and ex vivo models used in their study. In yet another study conducted by Subramaniam and Gupta, the authors found Hi-Ora to be effective in decreasing oral microbial load in chronic gingivitis patients in their study. The results of the present study as well were found to be statistically significant when compared between CHX and normal saline and Hi-Ora and normal saline groups (P < 0.0001), though insignificant between groups using CHX and Hi-Ora for both GI (P = 0.886) and PI (P = 0.928) scores in accordance with the findings of the studies conducted by Bhat et al., Shetty et al., Gupta et al. and Pathan et al. who observed no significant difference between Hi-Ora and CHX groups in their studies. In a similar study conducted by Malhotra et al., the authors supported the fact that though herbal mouthrinse (Herboral) was less effective than CHX, it was more acceptable to patients as an alternative to CHX.
Contrary to the findings of these studies, though Parwani et al. observed the least GI and PI scores in 0.2% CHX group followed by herbal mouthrinse group while the highest in the normal saline group. Herbal mouthrinse used in the study conducted by Parwani et al. was composed of babool chaal/Acacia arabica (20% w/v) as astringent, darim leaves/Punica granatum (10% w/v) as astringent, chameli leaves/Jasminum grandiflorum (10% w/v) as an anti-microbial, mulethi/Glycyrrhiza glabra (5% w/v) as astringent and neem/Azadirachta indica (2% w/v) as an astringent and anti-microbial agent while other contents (in small quantities) included alum (1.5% w/v), suhaga (1% w/v), kapoor (0.5% w/v), laung (1% w/v), and menthol (0.5% w/v).
Similarly, Biswas et al. and Vaish et al. also, observed CHX to be more efficacious in terms of improvement of GI and PI scores than herbal mouthrinse (Herboral), though both CHX and herbal mouthrinse were found to be equally effective in reducing bleeding on probing, a significant clinical indicator in assessing the severity of gingivitis in the affected patients. Furthermore, unlike CHX, herbal mouthrinse was not associated with discoloration of teeth or, unpleasant taste and was found to be better accepted by patients as against CHX. Nevertheless, the results obtained in the present study emphasize the need for further studies in this regard to substantiate the clinical efficacy of herbal mouthrinses with similar or, higher antimicrobial efficacy than CHX to overcome the well-known disadvantages associated with long-term use of CHX which is undoubtedly still considered the gold standard anti-plaque agents available.
Future research directions
A shorter follow-up period was one of the major limitations of the present study which mandates further longitudinal studies with larger sample sizes and follow-up durations to validate the sustainability of effects seen and consistency of results obtained in the present study. In addition, the recent introduction of molecular biology opens up new vistas and a new search of the role of potential biomarkers in diagnosis as well as in assessing the treatment outcomes in the gingival and periodontal disease over a period of time. The present study, thus, paves way for further studies in this regard wherein the improvement in clinical markers can, further, be correlated with the biomarkers of gingival and periodontal disease validating the success of treatment and efficacy of new therapeutic agents used during treatment.,,,,,,,
| Conclusions|| |
The results of the present study suggested Hi-Ora to be equally efficacious as 0.12% CHX in reducing the mean GI and PI scores in patients with chronic gingivitis, however, further multi-centric, randomized-controlled clinical and microbial trials with larger sample sizes are mandated to identify the exact mechanism of action in improving the clinical parameters and against different organisms to come to valid conclusions. The substantivity of herbal mouthrinses, also, needs further investigation for deriving long-term clinical benefits.
From the planning of the study to the conduct (data acquisition and analysis) and maintaining meticulous follow-up of the patients enrolled. Also, from manuscript preparation to editing and revisions done.
Ethical policy and institutional review board statement
The study protocol was approved by the Institutional Ethics Committee through letter approval number SIDS/IEC/07-377-2021.
Patient declaration of consent
(If in vivo study/case reports): A written, informed consent was obtained from each participant before their inclusion in the study.
The authors gratefully acknowledge all the patients who participated and contributed for the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Murakami S, Mealey BL, Mariotti A, Chapple ILC. Dental plaque-induced gingival conditions. J Periodontol 2018;89 Suppl 1:S17-27.
Trombelli L, Farina R, Silva CO, Tatakis DN. Plaque-induced gingivitis: Case definition and diagnostic considerations. J Clin Periodontol 2018;45 Suppl 20:S44-67.
Trombelli L, Farina R, Silva CO, Tatakis DN. Plaque-induced gingivitis: Case definition and diagnostic considerations. J Periodontol 2018;89 Suppl 1:S46-73.
Chapple ILC, Mealey BL, Van Dyke TE, Bartold PM, Dommisch H, Eickholz P, et al.
Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 world workshop on the classification of periodontal and peri-implant diseases and conditions. J Periodontol 2018;89 Suppl 1:S74-84.
Löe H. The gingival index, the plaque index and the retention index systems. J Periodontol 1967;38:l610-6.
Mali AM, Behal R, Gilda SS. Comparative evaluation of 0.1% turmeric mouthwash with 0.2% chlorhexidine gluconate in prevention of plaque and gingivitis: A clinical and microbiological study. J Indian Soc Periodontol 2012;16:386-91.
Narayan A, Mendon C. Comparing the effect of different mouthrinses on de novo plaque formation. J Contemp Dent Pract 2012;13:460-3.
Chow SC, Liu JP. Design and Analysis of Clinical Trials: Concepts and Methodologies. 2nd
Ed. New York: John Wiley and Sons; 1998.
Schulz KF, Altman DG, Moher D, Consort Group. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials. BMC Med 2010;8:18.
Loe h, silness j. Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontol Scand 1963;21:533-51.
Silness J, loe H. Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condtion. Acta Odontol Scand 1964;22:121-35.
Jaidka S, Somani R, Bajaj N, Jaidka R, Sharma S, Singh A. Comparative evaluation of various mouthwashes for their effect on oral health: An in-vivo
study. Int J Oral Care Res 2015;3:56-62.
Asiri FY, Alomri OM, Alghmlas AS, Gufran K, Sheehan SA, Shah AH. Evaluation of the efficacy of a commercially available herbal mouthwash on dental plaque and gingivitis: A double-blinded, parallel, randomized, controlled trial. J Int Oral Health 2016;8:224-6. [Full text]
Bhat N, Mitra R, Reddy JJ, Oza S, Vinayak KM. Evaluation of efficacy of chlorhexidine and a herbal mouthwash on dental plaque: An in-vitro
comparative study. Int J Pharm Bio Sci 2013;4:625-32.
Shetty S, Pillai S, Sridharan S, Satyanarayana A, Rahul A. Comparative efficacy of chlorhexidine and a herbal mouth rinse in patients with gingival inflammation: A clinical and microbiologic study. Asian J Pharm Technol Innov 2013;1:1-8.
Gupta D, Nayan S, Tippanawar HK, Patil GI, Jain A, Momin RK, et al.
Are herbal mouthwash efficacious over chlorhexidine on the dental plaque? Pharmacognosy Res 2015;7:277-81.
Pathan MM, Bhat KG, Joshi VM. Comparative evaluation of the efficacy of a herbal mouthwash and chlorhexidine mouthwash on select periodontal pathogens: An in vitro
and ex vivo
study. J Indian Soc Periodontol 2017;21:270-5.
] [Full text]
Subramaniam P, Gupta T. Efficacy of a herbal mouthrinse on oral microbial load in down syndrome children. Int J Herb Med 2013;1:50-4.
Malhotra R, Grover V, Kapoor A, Saxena D. Comparison of the effectiveness of a commercially available herbal mouthrinse with chlorhexidine gluconate at the clinical and patient level. J Indian Soc Periodontol 2011;15:349-52.
] [Full text]
Parwani SR, Parwani RN, Chitnis PJ, Dadlani HP, Prasad SV. Comparative evaluation of anti-plaque efficacy of herbal and 0.2% chlorhexidine gluconate mouthwash in a 4-day plaque re-growth study. J Indian Soc Periodontol 2013;17:72-7.
] [Full text]
Biswas G, Anup N, Acharya S, Kumawat H, Vishnani P, Swasti T. Evaluation of the efficacy of 0.2% chlorhexidine versus herbal oral rinse on plaque induced gingivitis: A randomized clinical trial. IOSR J Nurs Health Sci 2014;3:58-63.
Vaish S, Ahuja S, Dodwad V, Parkash H. Comparative evaluation of 0.2% chlorhexidine versus herbal oral rinse on plaque induced gingivitis. J Indian Assoc Public Health Dent 2012;10:55-62. [Full text]
Isola G, Polizzi A, Alibrandi A, Williams RC, Lo Giudice A. Analysis of galectin-3 levels as a source of coronary heart disease risk during periodontitis. J Periodontal Res 2021;56:597-605.
Isola G, Lo Giudice A, Polizzi A, Alibrandi A, Murabito P, Indelicato F. Identification of the different salivary Interleukin-6 profiles in patients with periodontitis: A cross-sectional study. Arch Oral Biol 2021;122:104997.
Isola G. Advances in biomarkers and diagnostics in periodontitis and oral diseases. Int J Environ Res Public Health 2021;18:1886.
Isola G, Polizzi A, Patini R, Ferlito S, Alibrandi A, Palazzo G. Association among serum and salivary A. Actinomycetemcomitans specific immunoglobulin antibodies and periodontitis. BMC Oral Health 2020;20:283.
Isola G, Polizzi A, Alibrandi A, Indelicato F, Ferlito S. Analysis of endothelin-1 concentrations in individuals with periodontitis. Sci Rep 2020;10:1652.
de Morais EF, Pinheiro JC, Leite RB, Santos PP, Barboza CA, Freitas RA. Matrix metalloproteinase-8 levels in periodontal disease patients: A systematic review. J Periodontal Res 2018;53:156-63.
Zhang L, Li X, Yan H, Huang L. Salivary matrix metalloproteinase (MMP)-8 as a biomarker for periodontitis: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore) 2018;97:e9642.
Gursoy UK, Könönen E, Pradhan-Palikhe P, Tervahartiala T, Pussinen PJ, Suominen-Taipale L, et al
. Salivary MMP-8, TIMP-1, and ICTP as markers of advanced periodontitis. J Clin Periodontol 2010;37:487-93.
[Table 1], [Table 2], [Table 3]