Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1) or alternatively activated (M2). However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states. Induction of specific macrophage functions is closely related to the surrounding environment that acts as a relevant orchestrator of macrophage functions. This phenomenon, termed polarization, results from cell/cell, cell/molecule interaction, governing macrophage functionality within the hosting tissues. Here, we summarized relevant cellular and molecular mechanisms driving macrophage polarization in “distant” pathological conditions, such as cancer, type 2 diabetes, atherosclerosis, and periodontitis that share macrophage-driven inflammation as a key feature, playing their dual role as killers (M1-like) and/or builders (M2-like). We also dissect the physio/pathological consequences related to macrophage polarization within selected chronic inflammatory diseases, placing polarized macrophages as a relevant hallmark, putative biomarkers, and possible target for prevention/therapy.

Inflammation, altered immune cell phenotype, and functions are key features shared by diverse chronic diseases, including cardiovascular, neurodegenerative diseases, diabetes, metabolic syndrome, and cancer. Natural killer cells are innate lymphoid cells primarily involved in the immune system response to non-self-components but their plasticity is largely influenced by the pathological microenvironment. Altered NK phenotype and function have been reported in several pathological conditions, basically related to impaired or enhanced toxicity. Here we reviewed and discussed the role of NKs in selected, different, and “distant” chronic diseases, cancer, diabetes, periodontitis, and atherosclerosis, placing NK cells as crucial orchestrator of these pathologic conditions.

SummaryAim. The aim of this study was to determine the concentration and the variations of salivary glucose in healthy patients who were sampled at five different intervals during the day. Materials and methods. Samples of un-stimulated saliva have been collected from 21 healthy patients using the drooling technique and they were divided into two categories. In the first category, patients were asked not to toothbrush their teeth in the 8 hours prior to collection of the salivary sample. Patients in the second category were instead asked to toothbrush 90 minutes before the collection of the first sample of saliva. The glucose concentration was measured in all patients via an enzymatic spectrophotometry. Patients have been selected following a strict inclusion criteria, which included <5% of plaque presence e according to the plaque Index and a total absence of oral disease that could possibly interfere with sample taking or oral fluid analysis. The average age of patients was 22,4±2,6 years old of which 45% were female and 55% were male. Samples were collected five times between 8 am and 12 pm, before and after breakfast. Data was statistically analyzed using the Skewness/Kurtosis Test, Shapiro-Wilk Test, Kruskal Wallis Test and Linear Regression Model, considering values of p<0,05 to be significant. Results.The average rate of un-stimulated salivary flow was 0,53±0,21 ml/min. There were no significant differences between salivary glucose values and salivary flow in female and male patients. However, we observed a typical trend which recurred for each patient and resembled a "pseudo-glycemic curve". Conclusions. The collected data suggests that glucose concentration results did not show statistically significant differences (p>0,078) which could however be due to the little number of patients assessed, nonetheless there is a trend, recalling a "pseudo-glycemic curve" not referable to changes in flow rates, probably due to glucose catabolism and shunt.

Background: A newly available gel containing hyaluronic acid (HA) and polyvinylpyrrolidone was tested for efficacy on traumatic oral ulcers (TOU) caused by fixed orthodontic appliances. Methods: A double-blind RCT was conducted to test the new gel versus a placebo. According to the sample size calculation, a total of 60 patients were considered sufficient and randomly allocated to one of the two groups out of a pool of 100 total patients who initially agreed to participate in the study. A VAS scale test and lesion measurements at T0, T1, and T2 were performed on the patients. Results: A total of 70 patients developed TOU, with 8 drop-outs; the intergroup comparison showed a statistically significant greater dimension of the lesion in the control group at T2 when compared to the test group. The pain experienced by the patients belonging to the test group was significantly lower than the pain in the patients in the control group Conclusions: Under the limitations of the study, the new formula might provide faster healing with less pain experienced by the patient when compared to a placebo.

This study compared the analgesic and anti-inflammatory efficacy of intra-alveolar administration of a thermosetting gel containing Doxycycline Hyclate 3% + Ketorolac Tromethamine 0.5% (Tg-DHKT) (Thermosetting gel, Monteresearch, Bollate, Italy) on patient discomfort after third molar surgery. This study was a single-blind, randomized clinical trial, including two study groups of39 and 41 patients each, who required surgical removal of a single mandibular impacted third molar. After the extraction the test group received an intra-alveolar injection with Tg-DHKT and the second group a thermosetting gel containing only Doxycycline Hyclate 3% (Tg-DH). Each patient's symptoms (pain, swelling, reddening, bleeding and body temperature) was assessed with a follow-up questionnaire (PoSSe scale). Nimesulide 100 mg, a painkiller, every 8 hours was prescribed to the Control and Test groups if necessary (maximum 3 doses); if they needed to assume it they were asked to mark it on the questionnaire. Results showed that on the second day after surgery pain, oedema and reddening decreased faster in the Control group (Tg-DH). There was no difference between the two groups when postoperative bleeding was evaluated. In both groups bleeding decreased in the same way, probably due to the mechanical characteristics of the gel itself. 46% of patients of the Test group did not require to take any painkiller at home. Our data demonstrate that the use of Tg-DHKT is less effective in the prevention of postoperative symptoms after third molar extraction compared to Tg-DH. However, almost half of patients in the Test group did not need to take more pain medication at home, suggesting that a single postoperative local administration of Tg-DHKT is a safe and effective concept for controlling pain, oedema and inflammation after third molar extraction.The surgical removal of impacted third molars is one of the most frequently performed procedures in oral surgery and afterwards complications such as post-operative pain, swelling and trismus may occur, and in some cases fever, during the first few postoperative days. As prostaglandins are presumed to be a primary mediator of acute postsurgical inflammatory changes, these patients, are therefore ideal clinical subjects for studying the effect of antiinflammatory agents on sequelae ofteeth extractions.