Changes in Salivary Parameters of Oral Immunity after Biologic Therapy for Inflammatory Bowel Disease

We previously observed that inflammatory bowel disease (IBD) may compromise oral host defense, as assessed by decreased salivary levels of immunoglobulin A (IgA) and myeloperoxidase (MPO). Biologic therapy with inhibitors of cytokines or adhesion molecules is increasingly used for patients with IBD. Little is known, however, about how this treatment modality affects the release and properties of saliva. Here, we aimed to determine how biologic therapy in patients who had not responded to previous standard treatment with conventional drugs affected the salivary concentration of IgA and MPO. To this end, unstimulated whole mixed saliva was collected before treatment or after 10–12 weeks of therapy from 27 patients with Crohn’s disease (CD) and 24 patients with ulcerative colitis (UC). After the induction phase of therapy with biologics, salivary levels of IgA and MPO increased significantly in UC, but not in CD patients. These increases were approximately 8-fold and 6-fold, for IgA and MPO, respectively. Moreover, these effects occurred in UC patients who responded successfully to therapy, but not in those who failed to improve. Furthermore, the relative increases in salivary IgA and MPO correlated with the relative decrease in UC severity, as assessed by the Mayo scale. These data indicate that the successful therapy with biologics in UC patients results also in improved oral host defense. However, it remains to be determined why such an effect does not occur during therapy for CD.

Inflammaging: Role in pathogenesis and molecular diagnostics of age-related dilated cardiomyopathy

Актуальность. В патогенезе дилатационной кардиомиопатии (ДКМП) у лиц старших возрастных групп важную роль играет инфламэйджинг и нарушение мелатонинобразующей функции эпифиза. Важной задачей молекулярной медицины является поиск сигнальных молекул - маркеров ДКМП. Цель работы - провести сравнительную оценку концентрации IL-1β, IL-6, Klotho, Sirt3, FGF23 и мелатонина в слюне у пациентов старших возрастных групп с ДКМП и без неё. Методы. Определение концентрации сигнальных молекул в слюне осуществляли методом иммуноферментного анализа с последующей статистической обработкой полученных данных. Результаты. У пациентов с ДКМП пожилого и старческого возраста концентрация маркеров инфламэйджинга (IL-1β, IL-6) в слюне повышалась в 8,6-19,1 раза по сравнению с этими показателями у лиц без ДКМП. Концентрация белка Klotho, ингибирующего синтез провоспалительных цитокинов, в слюне пациентов с ДКМП пожилого и старческого возраста была в 4,2-7,6 раза ниже по сравнению с этим показателем у лиц без ДКМП. У пациентов с ДКМП пожилого и старческого возраста концентрация в слюне мелатонина и регулируемого им Sirt3 была в 2,1-4,3 раза ниже по сравнению с этим показателем у лиц без ДКМП. Концентрация FGF23 в слюне не зависела от возраста пациентов и наличия ДКМП. Заключение. В патогенезе ДКМП у лиц старших возрастных групп важную роль играет инфламэйджинг. Об этом свидетельствует снижение синтеза белка Klotho и повышение уровня провоспалительных цитокинов IL-1β и IL-6. Другим звеном патогенеза ДКМП является снижение синтеза мелатонина и, как следствие, нарушение функции сигнального пути Mst1/Sirt3. Исследование концентрации IL-1β, IL-6, Klotho, SIRT3 и мелатонина в слюне может применяться для молекулярной диагностики ДКМП у лиц пожилого и старческого возраста. Background. Inflammaging and disorder of melatonin synthesis in the pineal gland play an important role in the pathogenesis of dilated cardiomyopathy (DC) in elderly and old people. An important objective of molecular medicine is searching for signal molecules, markers of DC. The aim of this work was to compare concentrations of IL-1β, IL-6, Klotho, Sirt3, FGF23, and melatonin in saliva of elderly and old DC patients and persons without DC. Methods. Concentrations of signal molecules were measured in saliva by ELISA. Results. Salivary concentrations of inflammaging markers (IL-1β, IL-6) in elderly and old DC patients were 8.6-19.1 times higher than in persons without DC. Salivary concentration of Klotho protein, an inhibitor of pro-inflammatory cytokine synthesis, was increased 4.2-7.6 times in elderly and old DC patients compared to the values in persons without DC. Salivary concentrations of melatonin and melatonin-regulated Sirt3 were decreased 2.1-4.3 times in elderly and old DC patients compared to the values in persons without DC. Salivary concentration of FGF23 did not depend on the age or presence of DC. Conclusion. Inflammaging plays in important role in the pathogenesis of DC in elderly and old people as evidenced by decreased synthesis of Klotho and increased levels of the pro-inflammatory cytokines IL-1β and IL-6. Another step in the DC pathogenesis is decreased melatonin synthesis and the resultant dysregulation of the Mst1/Sirt3 signaling way. Measuring concentrations of IL-1β, IL-6, Klotho, SIRT3, and melatonin in saliva can be used for molecular diagnostics of DC in elderly and old people.

Native α-Synuclein, 3-Nitrotyrosine Proteins, and Patterns of Nitro-α-Synuclein-Immunoreactive Inclusions in Saliva and Submandibulary Gland in Parkinson’s Disease

Background. Salivary α-synuclein (aSyn) and its nitrated form, or 3-nitrotyrosine-α-synuclein (3-NT-αSyn), hold promise as biomarkers for idiopathic Parkinson’s disease (IPD). Nitrative stress that is characterized by an excess of 3-nitrotyrosine proteins (3-NT-proteins) has been proposed as a pathogenic mechanism in IPD. The objective is to study the pathological role of native αSyn, 3-NT-αSyn, and 3-NT-proteins in the saliva and submandibulary glands of patients with IPD. Methods. The salivary and serum αSyn and 3-NT-proteins concentration is evaluated with ELISA in patients and controls. Correlations of αSyn and 3-NT-proteins content with clinical features of the disease are examined. Immunohistochemical 3-NT-αSyn expression in submandibulary gland sections is analyzed. Results. (a) Salivary concentration and saliva/serum ratios of native αSyn and 3-NT-proteins are similar in patients and controls; (b) salivary αSyn and 3-NT-proteins do not correlate with any clinical feature; and (c) three patterns of 3-NT-αSyn-positive inclusions are observed on histological sections: rounded “Lewy-type” aggregates of 10–25 µm in diameter, coarse deposits with varied morphology, and spheroid inclusions or bodies of 3–5 µm in diameter. “Lewy-type” and coarse inclusions are observed in the interlobular connective tissue of the gland, and small-sized bodies are located within the cytoplasm of duct cells. “Lewy-type” inclusions are only observed in patients, and the remaining patterns of inclusions are observed in both the patients and controls. Conclusions. The patients’ saliva presents a similar concentration of native αSyn and 3-nitrotyrosine-proteins than that of the controls, and no correlations with clinical features are found. These findings preclude the utility of native αSyn in the saliva as a biomarker, and they indicate the absence of nitrative stress in the saliva and serum of patients. As regards nitrated αSyn, “Lewy-type” inclusions expressing 3-NT-αSyn are observed in the patients, not the controls—a novel finding that suggests that a biopsy of the submandibulary gland, if proven safe, could be a useful technique for diagnosing IPD. Finally, to our knowledge, this is also the first description of 3-NT-αSyn-immunoreactive intracytoplasmic bodies in cells that are located outside the nervous system. These intracytoplasmic bodies are present in duct cells of submandibulary gland sections from all subjects regardless of their pathology, and they can represent an aging or involutional change. Further immunostaining studies with different antibodies and larger samples are needed to validate the data.

Multifocal Analysis of Acute Pain After Third Molar Removal

Background: To analyze the pain modulation capacity profile in a Brazilian population, the relationship between opioid receptor (OPRM1) and Catechol-O-methyltransferase (COMT) 1polymorphisms and pain modulation capacity was determined through preoperative pain modulation tests and acute postoperative pain control evaluation, swelling, and trismus in 200 volunteers undergoing lower third molar removal.Methods: Psychologic and clinical parameters were measured. Patient DNA was sequenced for single nucleotide polymorphisms in OPRM1 and COMT, and the salivary concentration of interleukin (IL)-2 (IL)-6, interferon (IFN)-γ and tumor necrosis factor (TNF)-α was evaluated. Primary outcomes were the influence of all predictors on the fluctuation of pain intensity using a visual analogue scale (VAS), and swelling and trismus on the 2nd and 7th postoperative days. Preoperative pain modulation capacity (CPM), pain catastrophizing scale (PCS), body mass index (BMI), and surgery duration and difficulty were evaluated.Results: Salivary concentration of IFN-γ and IL-2 as well as the duration of surgery influenced the fluctuation of postoperative pain in the VAS, and in the sum of the differences in pain intensity test at 8, 48, and 96 h. BMI influenced swelling, while both BMI and COMT haplotype influenced trismus on the 2nd postoperative day.Conclusion: Polymorphisms in COMT, salivary concentrations of IL-2 and IFN-γ, BMI, and duration of surgery were predictors for pain fluctuation, swelling, and trismus on the 2nd day after lower third molar extraction. This therapy was effective in controlling inflammatory symptomatology after lower third molar extraction and ibuprofen was well tolerated by patients.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT03169127.

Salivary MRP-8/14 and the presence of periodontitis-associated bacteria in children with bonded maxillary expansion treatment

Objectives The aim of this study was to investigate changes in saliva concentration of the inflammatory marker MRP-8/14 and the presence of some periodontitis-associated bacteria in patients with mixed dentition treated with a rigid acrylic, bonded maxillary expander. Methods Fifteen patients in mixed dentition treated with a bonded palatal expander were enrolled in this longitudinal study. Saliva samples were taken before the therapy, as well as in 2 weeks and 3, 6, 9, and 12 months after the beginning of the therapy. In each sample, the levels of MRP-8/14 were determined by ELISA and the presence of 11 bacteria was detected by PCR followed by DNA-DNA hybridization. Results Salivary concentration of MRP-8/14 and the amount of Tannerella forsythia, Treponema denticola, and Eikenella corrodens were significantly increased during treatment with bonded maxillary expander. These changes were transient and the maximal levels of MRP-8/14 and periodontitis-associated pathogens were observed 6–9 months after the beginning of the therapy. Conclusion Therapy with bonded maxillary results in higher MRP-8/14 levels and increased prevalence of some periodontitis-associated bacteria, namely T. forsythia, T. denticola, and E. corrodens. The results suggest the detection of salivary MRP-8/14 levels may be a potential tool to reflect the oral health status in children with fixed orthodontic treatment. Clinical relevance Our data suggest that the treatment with bonded maxillary expander might influence the oral health status and should be accompanied by the careful control of the oral health during the therapy.

Degree of Agreement Between Infant Serum and Salivary Concentration of Leptin and Adiponectin and Its Association With Infants’ Feeding

Background: Leptin and adiponectin, two adipokines involved in glucose and lipid metabolism, have been linked to regulation of growth in early infancy, energy balance, and metabolic disorders in childhood. The aim of this study was to determine if concentrations of leptin and adiponectin could be measured reliably in infants’ saliva, to evaluate the degree of agreement with infant serum levels, and to explore their association with infant feeding status. Methods: A total of 34 infants were recruited after birth and followed for 20 weeks. After log-transformation of the values, a Bland-Altman graphical approach was used to summarize the direction of the difference between the serum and saliva values. Repeated measures mixed modeling was used to evaluate differences over time in these outcomes by feeding status. Results: Mean concentration of salivary leptin and adiponectin in infants was 3.7 ( SD = .8) ng/mL and 2.9 ( SD = 0.7) ng/mL, respectively. The degree of agreement between serum and saliva for log-transformed leptin and adiponectin values were relatively robust, albeit with a non-zero bias between the two methods, given that serum values were greater than corresponding saliva values for both adipokines in all infants. Each of the four repeated measures mixed models (one for each adipokine measure) had a significant main effect; however, the interaction between time and feeding status was not significant in any of the models. Conclusion: This study demonstrated that leptin and adiponectin can be measured in infant saliva, but in some cases leptin concentrations may be more difficult to detect.

Concentration in Saliva and Antibacterial Effect of Xylitol Chewing Gum: In Vivo and In Vitro Study

Purpose. The saliva concentration of xylitol released from two chewing gums was recorded, the first containing xylitol as the only sweetener (100% xylitol) and the second containing only 22% of the polyol. In addition, the in vitro antibacterial effect of the two chewing gums was evaluated. Materials and Methods. The salivary concentration of Xylitol in 32 subjects was determined before and at 0.30, 1.00, 2.00, 5.00, and 10.00 min while using the chewing gums, and at 15.00, 20.00, and 25.00 min after the gums were discarded. In vitro antibacterial activity was determined on a pooled subgingival plaque sample obtained from four patients with periodontal disease. Cariogenic and periodontal bacteria were evaluated before and 15 min, 60 min, and 24 h after gum contact. Results. Using the 100% xylitol chewing gum, saliva levels increased bimodally, one peak after 30 s (1.49 ± 1.41 logμg/L) and a second one at a 10-min evaluation (1.41 ± 1.11 logμg/L); the 22% chewing gum peaked only two minute after contact (1.21 ± 1.24 logμg/L). Overall, a statistically significantly higher salivary concentration of xylitol was detected using the 100% xylitol gum. All bacteria decreased after the addition of the two chewing gums; the 100% gum achieved a greater decrease than the 22% gum. Conclusion. The use of both chewing gums increased the concentrations of xylitol in saliva, with a statistically significantly higher concentration using the 100% xylitol gum. Cariogenic and periodontal bacteria were reduced by both chewing gums; 100% xylitol gum produced the highest and longest lasting effect. This study opens up to the use of xylitol against periodontal disease.