Background and Objective Melatonin is synthesized naturally by pineal gland and responsible for regulation of sleep/waking cycle. It showed appreciated anti‐inflammatory and antioxidant properties. The aim of this randomized clinical trial (RCT) was to assess the additive effect of melatonin supplementation in insomniac individuals with generalized chronic periodontitis (gCP) after scaling and root planing (SRP). Material and Methods Seventy‐four gCP patients with primary insomnia participated in this 6‐month RCT and randomized into two groups. Melatonin group included 38 patients who were subjected to SRP with a 2‐month regimen of 10 mg oral melatonin capsule once daily before bedtime. In the control group, SRP was performed for 36 participants provided with matching placebo capsules. The primary treatment outcome was the measurement of clinical attachment level gain (CAL gain) after 3 and 6 months of therapy, whereas the measurements of pocket depth reduction (PD reduction), bleeding on probing (BOP %), and the changes in salivary TNF‐α levels and Athens insomnia scale (AIS) scores represented the secondary endpoints. Results Melatonin group showed significantly greater CAL gain and PD reduction measurements compared to the control group at 3 and 6 months of therapy, P < 0.01. Likewise, salivary TNF‐α levels and AIS scores were significantly lower in the melatonin group compared to placebo group. BOP% improved significantly in both groups without any difference. However, salivary TNF‐α levels exhibited no correlation with other clinical variables in both melatonin and placebo groups. Conclusion Daily dietary 10 mg of melatonin supplementation might serve as a viable adjunct to SRP that yielded significantly greater CAL gain and PD reduction and lower salivary TNF‐α levels and AIS scores in gCP patients with primary insomnia.

There is a significant prevalence of subjects with periodontitis presenting with other inflammatory conditions such as coronary heart disease, insulin resistance and arthritis. This pattern of disease presentation underscores the importance of inflammatory loading from chronic diseases, in driving their pathogeneses in a multidirectional manner. Pro-inflammatory cytokines and other agents play an important role in this process; for example, a single nucleotide polymorphism of the TNF-α gene is associated with significant periodontal attachment loss in patients with coronary heart disease. Changes in gene expression associated with inflammation and lipid metabolism in response to oral infection with the periodontal pathogen Porphyromonas gingivalis (Pg) have been demonstrated in mouse models, independent of the demonstration of atherosclerotic lesions. Insulin resistance is considered to be a chronic low-grade inflammatory condition, associated with altered glucose tolerance, hypertriglyceridemia, central obesity and coronary heart disease. It is accompanied by elevated levels of IL-1, IL-6 and TNF-α also relevant to the progression of periodontitis. There is evidence that uncontrolled periodontal disease contributes to maintenance of systemic diseases, including rheumatoid arthritis (RA), with increased risk of periodontitis in subjects with RA. The periodontal pathogen Pg is significant in contributing to citrullination of proteins resulting in immune dysregulation and autoimmune responses, seen in RA. However, they are both multifactorial chronic diseases with complex etiopathogeneses that affect their presentation. Consistent but weak associations are seen for surrogate markers of periodontitis such as tooth loss, with multiple systemic conditions. Effective treatment of periodontitis would be important in reducing systemic inflammatory loading from chronic local inflammation and in achieving systemic health. Lack of a consistent cause and effect relationship in all subjects would be influenced by genetic, epigenetic and other subject variables, although there are clear mechanisms that link the associations. This article includes an appraisal of patents and their applications.

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Common risk markers for periodontitis and prevalent systemic comorbidities indicate similarities in their progression and molecular mechanisms involved. Resultant pro-oxidant disease profiles provide scope for attenuating their pathogeneses with appropriate adjunctive antioxidants. Levels of oxidative stress markers 8-hydroxy-deoxguanosine (8-HOdG) and malondialdehyde (MDA) are significantly higher in periodontitis and other chronic inflammatory conditions. There is a clear link between periodontitis and diseases associated with significant systemic inflammatory loading, such as metabolic syndrome. Micro- and macro-nutrients have proven to be effective in curbing molecular mechanisms that generate reactive oxygen and nitrogen species. A Mediterranean diet rich in fruits, vegetables, legumes, whole grain, nuts, fish, olive oil and red wine in moderation, could be attributed to the lower occurrence of cardiovascular disease, insulin resistance and other inflammatory diseases in this region. A significant number of naturally occurring flavonoids have been identified in these products. Flavonoids comprising flavonols, flavones and isoflavones are potent free radical scavengers, effective in inhibiting lipid peroxidation, with anti-atherosclerotic and antihypertensive effects.The phenolic compound oleocanthal isolated in virgin olive oil has similar anti-inflammatory actions to that of ibuprofen. The anti-atherogenic effects of MUFA and PUFA in nuts, enhance endothelial function by reducing total cholesterol, oxidized LDL, hs-CRP, sVCAM-1 levels, lipids, lipoproteins and inflammatory markers. Epigenetics influenced by environmental factors and interactions between genes and nutrients, are important considerations in influencing these effects. Using antioxidants as therapeutic adjuncts could enhance the antioxidant capacity of an inherent glutathione system and overcome oxidative effects, thereby mitigating therapeutic side-effects.

Renal transplant recipients (RTRs) are regarded to be predisposed to oral candidiasis. This study was undertaken to evaluate the activity of hydrolytic enzymes in strains causing oral candidiasis in RTR. A total of 123 Candida albicans and 10 Candida krusei strains were isolated from 200 RTRs (39 RTRs suffered from symptomatic candidiasis, the remaining patients had no clinical symptoms of infection). All fungi were identified based on routine mycological procedures. Because of a small number of non-albicans strains, only C. albicans isolates were compared for enzymatic activity. The activity of 19 hydrolytic enzymes was assessed by API ZYM(®) test. The usage of mycophenolate mofetil was connected with higher ratio of clinically apparent oral candidiasis compared to immunosuppressive regimens without this drug (74.4% vs. 46.8%, respectively, P < 0.01). Candida albicans from RTRs showed higher enzymatic activity compared with strains from immunocompetent patients. Only two enzymes were found to be more active in C. albicans causing symptomatic candidiasis in RTRs (cystine arylamidase: P = 0.001, and α-fucosidase: P = 0.01) compared with saprophytic strains. Atrophic candidiasis showed higher activity of esterase lipase (C8) and α-mannosidase compared with the pseudomembraneous type. We suggest that the enhanced enzymatic activity is responsible for higher invasiveness of Candida residing in the oral cavity of RTRs.