Risk Factor For Systemic Diseases Research Articles

Generalized Pustular Psoriasis and Systemic Organ Dysfunctions.

This review explores the intricate relationship between generalized pustular psoriasis (GPP) and various systemic diseases, shedding light on the broader impacts of this severe skin condition beyond its primary dermatological manifestations. GPP is identified as not only a profound contributor to skin pathology but also a significant risk factor for systemic diseases affecting cardiovascular, hepatic, renal, pulmonary, and skeletal systems, as well as associated with an increased incidence of anemia, depression, anxiety, and arthritis. The research highlights the complex interplay of cytokines, particularly IL-17 and IL-36, which are central to the pathophysiology of GPP and implicated in the exacerbation of systemic conditions. Key findings indicate a higher incidence of cardiovascular events in GPP patients compared to those with other severe forms of psoriasis, notably with a stronger correlation between myocardial infarction history and GPP development. Liver disturbances, frequently reversible upon psoriasis remission, suggest a cytokine-mediated link to hepatic health. Renal dysfunction appears elevated in GPP sufferers, with IL-17 and IL-36 potentially driving renal fibrosis. Similarly, interstitial lung disease and osteoporosis in GPP patients underscore the systemic reach of inflammatory processes initiated in the skin. The associations with anemia, depression, anxiety, and arthritis further complicate the clinical management of GPP, requiring a multidisciplinary approach. The study concludes that managing GPP effectively requires a holistic approach that addresses both the cutaneous and systemic dimensions of the disease, advocating for continued research into the mechanisms that connect GPP with broader health implications to refine therapeutic strategies.

Oral health and multimorbidity: is diet the chicken or the egg?

Oral health is a critical component of overall health and well-being, not just the absence of disease. The objective of this review paper is to describe relationships among diet, nutrition and oral and systemic diseases that contribute to multimorbidity. Diet- and nutrient-related risk factors for oral diseases include high intakes of free sugars, low intakes of fruits and vegetables and nutrient-poor diets which are similar to diet- and nutrient-related risk factors for systemic diseases. Oral diseases are chronic diseases. Once the disease process is initiated, it persists throughout the lifespan. Pain and tissue loss from oral disease leads to oral dysfunction which contributes to impaired biting, chewing, oral motility and swallowing. Oral dysfunction makes it difficult to eat nutrient-dense whole grains, fruits and vegetables associated with a healthy diet. Early childhood caries (ECC) associated with frequent intake of free sugars is one of the first manifestations of oral disease. The presence of ECC is our 'canary in the coal mine' for diet-related chronic diseases. The dietary sugars causing ECC are not complementary to an Eatwell Guide compliant diet, but rather consistent with a diet high in energy-dense, nutrient-poor foods - typically ultra-processed in nature. This diet generally deteriorates throughout childhood, adolescence and adulthood increasing the risk of diet-related chronic diseases. Recognition of ECC is an opportunity to intervene and disrupt the pathway to multimorbidities. Disruption of this pathway will reduce the risk of multimorbidities and enable individuals to fully engage in society throughout the lifespan.

Obstructive Sleep Apnea Among Obese Children in Tabuk City, Saudi Arabia.

Introduction Obstructive sleep apnea (OSA) is prevalent among children, impacting their well-being. Obesity and related morbidity may lead to serious health disorders. In obese children, OSA may be a risk factor for systemic diseases that negatively affect their quality of life. This study explored the correlation between obesity and OSA among children aged five to 14 years in Tabuk, Saudi Arabia. Methods This cross-sectional study employed an online questionnaire for the parents of 517 children, assessing sociodemographic variables, medical history, and OSA symptoms. The data analysis used Statistical Product and Service Solutions (SPSS; IBM SPSS Statistics for Windows, Armonk, NY) software, employing descriptive and inferential statistics. Results The children were predominantly male (281, 54.4%) and from Tabuk (405, 78.3%), with 158 (30.6%) classified as obese. Symptoms such as snoring (191, 36.9%), daytime fatigue (195, 37.7%), and impact on daily activities (79, 15.3%) were prevalent. OSA scores significantly correlated with BMI categories (p < 0.001), family history of OSA (p < 0.001), and medical conditions including diabetes, hypertension, and high cholesterol (p < 0.05). Correlations showed weak positive associations of age (ρ = 0.159) and height (ρ = 0.229) with OSA score, whereas a strong correlation existed between weight (ρ = 0.531) and OSA score (p < 0.001). Conclusion Obesity demonstrated a strong association with OSA severity among children in Tabuk. Higher BMI categories, a family history of OSA, and certain medical conditions correlated significantly with increased OSA scores. Although age and height displayed weaker associations, weight emerged as a major contributing factor to OSA severity. These findings emphasize the importance of addressing obesity in managing pediatric OSA, advocating for early interventions to mitigate its impact on children's health and well-being.

Porphyromonas gingivalis-induced periodontitis could contribute to cognitive impairment in Sprague-Dawley rats via the P38 MAPK signaling pathway.

Periodontitis is one of the most common oral diseases and has been shown to be a risk factor for systemic diseases. Our aim was to investigate the relationship between periodontitis and cognitive impairment and to explore the role of the P38 MAPK signaling pathway in this process. We established a periodontitis model by ligating the first molars of SD rats with silk thread and injecting Porphyromonas gingivalis (P. gingivalis) or P. gingivalis plus the P38 MAPK inhibitor SB203580 at the same time for ten weeks. We assessed alveolar bone resorption and spatial learning and memory using microcomputed tomography and the Morris water maze test, respectively. We used transcriptome sequencing to explore the genetic differences between the groups. The gingival tissue, peripheral blood and hippocampal tissue were assessed for the cytokines TNF-α, IL-1β, IL-6, IL-8 and C reactive protein (CRP) with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). We observed the presence of P. gingivalis in the hippocampus of rats by paraffin-fluorescence in situ hybridization (FISH). We determined the activation of microglia by immunofluorescence. Finally, Western blot analysis was employed to determine the expression of amyloid precursor protein (APP), β-site APP-cleaving enzyme 1 (BACE1) and P38MAPK pathway activation. We demonstrated that silk ligature-induced periodontitis plus injection of P. gingivalis into subgingival tissue could lead to memory and cognitive impairment. Transcriptome sequencing results suggested that there were neurodegenerative diseases in the P. gingivalis group, and the MWM test showed that periodontitis reduced the spatial learning and memory ability of mild cognitive impairment (MCI) model rats. We found high levels of inflammatory factors (TNF-α, IL-1β, IL-6, and IL-8) and CRP in the gingiva, peripheral blood and hippocampus, and the expression of APP and BACE1 was upregulated, as was the P38 MAPK pathway activation. Activated microglia and the presence of P. gingivalis were also found in the hippocampus. P38 MAPK inhibitors mitigated all of these changes. Our findings strongly suggest that topical application of P. gingivalis increases the inflammatory burden in the peripheral and central nervous systems (CNS) and that neuroinflammation induced by activation of P38 MAPK leads to impaired learning and memory in SD rats. It can also modulate APP processing. Therefore, P38 MAPK may serve as a linking pathway between periodontitis and cognitive impairment.

Clinical Microbial Identification of Severe Oral Infections by MALDI-TOF Mass Spectrometry in Stockholm County: an 11-Year (2010 to 2020) Epidemiological Investigation.

Growing evidence suggests that oral infections can modify the course of systemic diseases. To date, epidemiological data on microbial oral infections are scarce. Here, we performed a comprehensive analysis of the trend and microbial diversity in oral infection specimens referred for clinical microbiology analysis from 2010 to 2020. The microbes were isolated by culture and were identified via matrix-assisted laser desorption ionization-time of flight mass spectrometry technology (MALDI-TOF MS) throughout the study period. A total of 1,014 referred samples from dental clinics in Stockholm County with dentoalveolar abscesses and jaw osteomyelitis being the main reason were identified. Overall, the microbial composition was dominated by Firmicutes (51%), followed by Bacteroidetes (19%), Proteobacteria (12%), and Actinobacteria (5%). At the genus level, Streptococcus spp. (36%), Prevotella spp. (18%), and Staphylococcus spp. (11%) were among the most frequently reported. Interestingly, a strong increase in trend was noted for Streptococcus anginosus, Streptococcus mitis, Streptococcus sanguinis, Eikenella corrodens, Actinomyces spp., Aggregatibacter aphrophilus, Staphylococcus epidermidis, and Granulicatella adiacens during the study time (R = 0.66 to 0.89, P < 0.05), and a minor increase was noted for Enterococcus faecalis and Klebsiella spp., whereas steady levels were noted for most of the others. The present study shows the diversity of bacteria that have been involved in dental infections during the last decade in the capital of Sweden, as well as the emerging oral microbiota trend, with clear clinical implications on the oral-systemic link. IMPORTANCE Oral diseases and associated microbes are a risk factor for systemic diseases and can change the courses of these diseases. To date, epidemiological data on microbial oral infections are scarce, and longitudinal reports are lacking. We present for the first time the microbial composition of severe oral bacterial infections determined via the MALDI-TOF mass spectrometry technique in a comprehensive study between 2010 and 2020 (11 years) in Stockholm County. The trend and microbial diversity of oral infections were analyzed on referred clinical microbiological samples and were processed by standardized protocols. Trend increase was noted for Streptococcus anginosus, Streptococcus mitis, Streptococcus sanguinis, Eikenella corrodens, Actinomyces spp., Aggregatibacter aphrophilus, Staphylococcus epidermidis, Granulicatella adiacens, Enterococcus faecalis, and Klebsiella spp. Our results provide new insights into the diversity and trend of oral microbiota that were involved in serious oral infections over the past decade in the capital of Sweden and may influence the oral-systemic link.

Nanoparticulate cell-free DNA scavenger for treating inflammatory bone loss in periodontitis

Periodontitis is a common type of inflammatory bone loss and a risk factor for systemic diseases. The pathogenesis of periodontitis involves inflammatory dysregulation, which represents a target for new therapeutic strategies to treat periodontitis. After establishing the correlation of cell-free DNA (cfDNA) level with periodontitis in patient samples, we test the hypothesis that the cfDNA-scavenging approach will benefit periodontitis treatment. We create a nanoparticulate cfDNA scavenger specific for periodontitis by coating selenium-doped hydroxyapatite nanoparticles (SeHANs) with cationic polyamidoamine dendrimers (PAMAM-G3), namely G3@SeHANs, and compare the activities of G3@SeHANs with those of soluble PAMAM-G3 polymer. Both G3@SeHANs and PAMAM-G3 inhibit periodontitis-related proinflammation in vitro by scavenging cfDNA and alleviate inflammatory bone loss in a mouse model of ligature-induced periodontitis. G3@SeHANs also regulate the mononuclear phagocyte system in a periodontitis environment, promoting the M2 over the M1 macrophage phenotype. G3@SeHANs show greater therapeutic effects than PAMAM-G3 in reducing proinflammation and alveolar bone loss in vivo. Our findings demonstrate the importance of cfDNA in periodontitis and the potential for using hydroxyapatite-based nanoparticulate cfDNA scavengers to ameliorate periodontitis.

A cross-sectional study assessing the relationship between non-alcoholic fatty liver disease and periodontal disease

The risk factors for non-alcoholic fatty liver disease (NAFLD) progression are not completely known. Porphyromonasgingivalis infection is a risk factor for systemic diseases. We investigated the association of P.gingivalis infection with the risk of non-alcoholic steatohepatitis progression. Here, hematological tests, periodontal examination, and saliva collection were performed for 164 patients with NAFLD. P.gingivalis was identified in saliva using polymerase chain reaction. Hepatic steatosis and stiffness were evaluated using vibration-controlled transient elastography (VCTE) and magnetic resonance imaging. In patients with NAFLD, P.gingivalis positivity (P.gingivalis ratio ≥ 0.01%) in saliva correlated with liver stiffness determined using magnetic resonance elastography (MRE; p < 0.0001). A P.gingivalis ratio of 0.01% corresponds to 100,000 cells/mL and indicates the proportion of P.gingivalis in the total number of bacteria in the oral cavity. Patients with NAFLD and advanced fibrosis on MRE showed significantly elevated endotoxin activity; those who had > 10 periodontal pockets with depths ≥ 4 mm had significantly increased hepatic stiffness on both VCTE and MRE.

Oral health in patients with severe inflammatory dermatologic and rheumatologic disease.

Poor oral health (OH) is a risk factor for systemic disease and lower quality of life (QoL). Patients with inflammatory dermatologic/rheumatologic diseases report more oral discomfort, dry mouth, and periodontal disease than controls. Medications used to treat these conditions can also adversely affect OH. The aim was to assess the OH of patients with chronic inflammatory dermatologic/rheumatologic diseases treated with systemic/biologic therapy, compared to controls. Patients with chronic inflammatory dermatologic/rheumatologic diseases treated with systemic/biologic therapy were recruited from outpatient clinics across two university hospitals. All patients had a standardized World Health Organisation OH assessment performed consisting of an OH exam and questionnaire. Age- and sex-matched controls without chronic inflammatory disease were recruited from a pigmented lesion clinic. Charts of patients with chronic inflammatory dermatologic/rheumatologic diseases were reviewed to assess OH documentation. One hundred patients were examined (50 cases and 50 controls). Patients with inflammatory dermatologic/rheumatologic diseases (cases) had poorer periodontal status (mean loss of attachment 6.9mm vs. 1.9mm controls, p=0.01), more missing teeth (mean 7.7 vs. 4.4 controls, p=0.029), more dry mouth (82% vs. 20% controls, p=0.001), and less frequent tooth brushing (60% vs. 80% controls, p=0.037). Of 250 patient charts which were reviewed, 98.4% (n=246) had no documentation of OH. Patients with severe inflammatory dermatologic/rheumatologic conditions have poorer OH and OH-related QoL. Clinicians should appreciate the risk of poor OH in this cohort and have a low threshold for involving OH professionals in care pathways for severe inflammatory disease.

&lt;strong&gt;The effect of Indian jujube leaves extract in inhibiting the growth of &lt;em&gt;Porphyromonas gingivalis&lt;/em&gt;&lt;/strong&gt;

Introduction: Periodontitis is an inflammatory disease that destroys tooth-supporting tissues and is associated with increased risk factors for systemic diseases. The main pathogen of periodontitis is the bacteria P. gingivalis, a Gram-negative, anaerobic, pleomorphic, coccobacillus, non-motile, and saccharolytic. The leaves of Indian jujube (Ziziphus mauritiana Lam.) have the main bioactive compounds such as saponins, tannins, and flavonoids which have antimicrobial activities against pathogenic microorganisms. This study aims to analyse various concentrations of the ethanol extract of Indian jujube leaves against P. gingivalis. Methods: The method used in this study was the disc diffusion test based on the Clinical and Laboratory Standard Institute. P. gingivalis preparation and the fresh leaves of Indian jujube collected from one of the plantations in Probolinggo, East Java. In this study, tests used various concentrations of Indian jujube leaves extract, namely 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100%. Data antibacterial activity was classified according to David and Stout’s inhibition zone classification. Results: Indian jujube leaves extract with a concentration between 10-30% had weak antibacterial activity, 40-60% had moderate antibacterial activity, and 70-100% had strong antibacterial activity. The largest inhibitory zone diameter against P. gingivalis was found at a concentration of 100%. Conclusion: Indian jujube leaves extract starting from a concentration of 70% can inhibit the growth of P. gingivalis with strong antibacterial activity.

Antibacterial activity of ethanol extract of Beluntas leaves on Streptococcus mutans, Porphyromonas gingivalis, and Enterococcus faecalis

Introduction: Individuals with poor oral health have a greater risk factor for systemic diseases. Caries, periodontal disease, and root canal infections are a common dental and oral diseases caused by dominance of Streptococcus mutans, Porphyromonas gingivalis, and Enterococcus faecalis bacteria (S. mutans, P. gingivalis, and E. faecalis). An alternative way to prevent dental and oral diseases is to use herbal medicine as one of the active ingredients for mouthwash or toothpaste. One of the herbs that can be used is Beluntas leaves (Pluchea indica (L.) Less leaves). The objective of study was to analyze the antibacterial activity of ethanol extract of Pluchea indica (L.) Less leaves on the growth of Streptococcus mutans, Porphyromonas gingivalis, and Enterococcus faecalis. Methods: This research was experimental laboratory with post test only control design, using disk diffusion method. There were five concentrations (2.5, 3.5, 4.5, 5.5 and 6.5%, positive controls, and negative controls. Data analysis was performed using One Way Anova and post Hoc test. Results: The ethanol extract of Pluchea indica (L.) Less leaves has moderate-strong antibacterial activity against Streptococcus mutans, Porphyromonas gingivalis, and Enterococcus faecalis. The largest diameter of inhibitory zone in Enterococcus faecalis at a concentration of 6.5% followed by Streptococcus mutans and Porphyromonas gingivalis at the same concentration and the smallest diameter of inhibition zone in Porphyromonas gingivalis, followed by Enterococcus faecalis and Streptococcus mutans at 2.5% concentration. Conclusion: The ethanol extract of Pluchea indica (L.) Less leaves with a concentration of 2.5, 3.5, 4.5, 5.5, and 6.5% has antibacterial activity in inhibiting the growth of Streptococcus mutans, Porphyromonas gingivalis, and Enterococcus faecalis.

Clinic epidemiological evaluation of co morbidities in patients with psoriasis in a tertiary care hospital

Background: Psoriasis is a common disease presented to the dermatology clinics. There are several reports concerning co morbidities in patients with psoriasis. Some of them include diabetes mellitus, hypertension, dyslipidemia, obesity, IHD, ulcerative colitis. Hence, we in the present study tried to evaluate the existing comorbidities in patients diagnosed with psoriasis in presenting to our hospital. Methods: This study was conducted in the Department of Dermatology, Venereology, and Leprosy, Prathima Institute of Medical Sciences, Karimnagar. This case-control study evaluated the prevalence of diabetes mellitus, hypertension, obesity, dyslipidemia and metabolic syndrome in patients with psoriasis. The existence of hypertension, diabetes mellitus, dyslipidemia, obesity was determined by standard criteria. The data was recorded and analyzed using SPSS version 17 for p values. Results: BSL (Blood Sugar Level) derangement as increased fasting BSL was observed in 23 (23%) cases compared to 8(8%) controls. There was a statistically significant difference between psoriatic cases and controls. The total number of male patients with raised waist circumference was 24 (33.8%) compared to 9(13.2%) controls. There was a statistically significant association of raised waist circumference in psoriasis cases compared to controls, the p-value was &lt;0.004. The existence of metabolic syndrome was 27% in the study group and 8% in the control group the p values were &lt;0.004 and significant. Conclusion: The results of the present shows that there is a significant prevalence of psoriasis in males as compared to females. There is a significant association of metabolic syndrome in patients with psoriasis. Hence all the patients with psoriasis need to be evaluated for metabolic syndrome which may be a risk factor for systemic diseases.

Relationship between NAFLD and Periodontal Disease from the View of Clinical and Basic Research, and Immunological Response.

Periodontal disease is an inflammatory disease caused by pathogenic oral microorganisms that leads to the destruction of alveolar bone and connective tissues around the teeth. Although many studies have shown that periodontal disease is a risk factor for systemic diseases, such as type 2 diabetes and cardiovascular diseases, the relationship between nonalcoholic fatty liver disease (NAFLD) and periodontal disease has not yet been clarified. Thus, the purpose of this review was to reveal the relationship between NAFLD and periodontal disease based on epidemiological studies, basic research, and immunology. Many cross-sectional and prospective epidemiological studies have indicated that periodontal disease is a risk factor for NAFLD. An in vivo animal model revealed that infection with periodontopathic bacteria accelerates the progression of NAFLD accompanied by enhanced steatosis. Moreover, the detection of periodontopathic bacteria in the liver may demonstrate that the bacteria have a direct impact on NAFLD. Furthermore, Porphyromonas gingivalis lipopolysaccharide induces inflammation and accumulation of intracellular lipids in hepatocytes. Th17 may be a key molecule for explaining the relationship between periodontal disease and NAFLD. In this review, we attempted to establish that oral health is essential for systemic health, especially in patients with NAFLD.

Endotoxemia by Porphyromonas gingivalis Alters Endocrine Functions in Brown Adipose Tissue.

Improvement of obesity is important for increasing longevity. The characteristics, size, and function of adipocytes are altered in patients with obesity. Adipose tissue is not only an energy storage but also an endocrine organ. Alteration of endocrine activities in adipose tissue, among them the functional decline of brown adipose tissue (BAT), is associated with obesity. Periodontal disease is a risk factor for systemic diseases since endotoxemia is caused by periodontal bacteria. However, the effect of periodontal disease on obesity remains unclear. Thus, this study aimed to investigate the effect of endotoxemia due to Porphyromonas gingivalis, a prominent cause of periodontal disease, on the BAT. Herein, endotoxemia was induced in 12-week-old C57BL/6J mice through intravenous injection of sonicated 108 CFU of P. gingivalis (Pg) or saline (control [Co]) once. Eighteen hours later, despite no inflammatory M1 macrophage infiltration, inflammation-related genes were upregulated exclusively in the BAT of Pg mice compared with Co mice. Although no marked histological changes were observed in adipose tissues, expressions of genes related to lipolysis, Lipe and Pnpla2 were downregulated after P. gingivalis injection in BAT. Furthermore, expression of Pparg and Adipoq was downregulated only in the BAT but not in the white adipose tissues, along with downregulation of Ucp1 and Cidea expression, which are BAT-specific markers, in Pg mice. Microarray analysis of the BAT showed 106 differentially expressed genes between Co and Pg mice. Gene set enrichment analysis revealed that the cholesterol homeostasis gene set and PI3/Akt/mTOR signaling gene set in BAT were downregulated, whereas the TGF-β signaling gene set was enriched in Pg mice. Overall, intravenous injection of sonicated P. gingivalis altered the endocrine functions of the BAT in mice. This study indicates that endotoxemia by P. gingivalis potentially affects obesity by disrupting BAT function.

Bone marrow stem cells therapy alleviates vascular injury in a chronic obstructive pulmonary disease‑obstructive sleep apnea overlap syndrome rat model.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are highly prevalent potential risk factors for systemic disease. Previous studies have reported that COPD and OSA are major independent risk factors for cardio- or cerebrovascular diseases. The present study aimed to investigate the role of bone marrow mesenchymal stem cells (BMSCs) on vascular injury in a COPD-OSA overlap syndrome (OS) rat model. Rats were randomly divided into three groups: Sham, OS model and BMSC. BMSC localization in major organs was detected via confocal laser fluorescence microscopy, and the aortic tissue pathological changes and related genes were measured using hematoxylin & eosin and Masson staining. Genes associated with vascular endothelial cell injury, including endothelin 1, vascular cell adhesion molecule 1 and endothelial nitric oxide synthase, were detected via reverse transcription-quantitative PCR and western blotting. Apoptosis of vascular endothelial cells was detected using TUNEL and immunofluorescence assays. The endothelial cell marker CD31 in injured vessels was analyzed via immunohistochemistry. BMSCs migrated into the heart, liver, spleen, lung, kidney, brain and aorta in the OS model. The green fluorescence expression of BMSCs demonstrated the highest level in the lung, followed by the aorta. Aortic tissue had a more severe vascular injury and increased apoptosis in the model group compared with the BMSC group. Vascular endothelial cell apoptosis was decreased in the BMSC group compared with the model group. The findings suggested that BMSCs could repair vascular injury by inhibiting endothelial cell damage and apoptosis. These data provide a theoretical basis for the treatment of cardiovascular diseases caused by OS with BMSCs.

IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood-Brain Barrier.

Background: Periodontal disease (PD) is a risk factor for systemic diseases, including neurodegenerative diseases. The role of the local and systemic inflammation induced by PD in neuroinflammation currently remains unclear. The present study investigated the involvement of periodontal inflammation in neuroinflammation and blood–brain barrier (BBB) disruption. Methods: To induce PD in mice (c57/BL6), a ligature was placed around the second maxillary molar. Periodontal, systemic, and neuroinflammation were assessed based on the inflammatory cytokine mRNA or protein levels using qPCR and ELISA. The BBB permeability was evaluated by the mRNA levels and protein levels of tight junction-related proteins in the hippocampus using qPCR and immunofluorescence. Dextran tracing in the hippocampus was also conducted to examine the role of periodontal inflammation in BBB disruption. Results: The TNF-α, IL-1β, and IL-6 levels markedly increased in gingival tissue 1 week after ligation. The IL-6 serum levels were also increased by ligature-induced PD. In the hippocampus, the IL-1β mRNA expression levels were significantly increased by ligature-induced PD through serum IL-6. The ligature-induced PD decreased the claudin 5 expression levels in the hippocampus, and the neutralization of IL-6 restored its levels. The extravascular 3-kDa dextran levels were increased by ligature-induced PD. Conclusions: These results suggest that the periodontal inflammation-induced expression of IL-6 is related to neuroinflammation and BBB disruption in the hippocampus, ultimately leading to cognitive impairment. Periodontal therapy may protect against neurodegenerative diseases.

Periodontitis Induced by P. gingivalis-LPS Is Associated With Neuroinflammation and Learning and Memory Impairment in Sprague-Dawley Rats.

BackgroundPeriodontitis is one of the most common oral diseases and is a potential risk factor for systemic diseases. In this study, we aimed to investigate the association between periodontitis and learning and memory impairment.MethodsWe established a periodontitis model by topical application of Porphyromonas gingivalis lipopolysaccharide (P. gingivalis-LPS) into the palatal gingival sulcus of the maxillary first molars of 10-week-old male rats for a 10-week period. We assessed alveolar bone resorption using micro–computed tomography analysis and learning and memory ability using the Morris water maze test. We determined the levels of cytokines [interleukin (IL)-1β, IL-6, IL-8, and IL-21] and LPS in the peripheral blood and cortex, as well as toll-like receptor 4 (TLR4)/NF-κB signaling pathway activation, using reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot. We determined activation of microglia and astrocytes, expression of Aβ1-42, APP and Tau by immunohistochemistry. Finally, we measured the expression of amyloid precursor protein (APP) and its key secretases, as well as the Aβ1-40/1-42 ratio, by RT-PCR, western blot, and ELISA.ResultsWe found that periodontitis induced learning and memory impairment in the rats. Further, we observed that it induced significant alveolar bone resorption. There was an increase in the levels of inflammatory cytokines and LPS. Moreover, we confirmed TLR4/NF-κB signaling pathway activation. We also observed activated microglia and astrocytes with enlarged cell bodies and irregular protrusions. Finally, we observed the promotion of β- and γ-secretases APP processing.ConclusionOur findings indicated that periodontitis was associated with learning and memory impairment, probably induced by neuroinflammation via activating the TLR4/NF-κB signaling pathway. Furthermore, abnormal APP processing could be involved in this progress.

Serum migration inhibitory factor levels in periodontal health and disease, its correlation with clinical parameters.

Periodontal infections are an important risk factor for systemic disease and are driven primarily by the cytokines. Migration Inhibitory Factor (MIF) is a key cytokine which mediates acute and chronic inflammation alongside, a molecular link between chronic inflammation and immune mediated conditions. Hence, the present study was carried to measure the serum MIF levels in periodontal health, disease and to correlate the levels with the clinical parameters. Sixty subjects were divided into three groups (each group n = 20) based on the gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL) as group I healthy; group II gingivitis; and group III chronic periodontitis. The serum MIF level was measured using quantitative sandwich enzyme immunoassay technique. Highest level was detected in Group III with a mean of 71.8 ng/ml and the lowest in group I (6.1 ng/ml). Serum MIF levels did not correlate with the clinical parameters. Increased serum MIF levels in chronic periodontitis patients suggest its role as an inflammatory biomarker and may have a role in inflating the systemic inflammation. Summary: Serum Migration inhibitory factor can be used as an inflammatory marker for periodontal disease.

Saliva and Serum Immune Responses in Apical Periodontitis.

Apical periodontitis is an inflammatory reaction at the apex of an infected tooth. Its microbiota resembles that of marginal periodontitis and may induce local and systemic antibodies binding to bacteria- and host-derived epitopes. Our aim was to investigate the features of the adaptive immune response in apical periodontitis. The present Parogene cohort (n = 453) comprises patients with cardiac symptoms. Clinical and radiographic oral examination was performed to diagnose apical and marginal periodontitis. A three-category endodontic lesion score was designed. Antibodies binding to the bacteria- and host-derived epitopes were determined from saliva and serum, and bacterial compositions were examined from saliva and subgingival samples. The significant ORs (95% CI) for the highest endodontic scores were observed for saliva IgA and IgG to bacterial antigens (2.90 (1.01–8.33) and 4.91 (2.48–9.71)/log10 unit), saliva cross-reacting IgG (2.10 (1.48–2.97)), serum IgG to bacterial antigens (4.66 (1.22–10.1)), and Gram-negative subgingival species (1.98 (1.16–3.37)). In a subgroup without marginal periodontitis, only saliva IgG against bacterial antigens associated with untreated apical periodontitis (4.77 (1.05–21.7)). Apical periodontitis associates with versatile adaptive immune responses against both bacterial- and host-derived epitopes independently of marginal periodontitis. Saliva immunoglobulins could be useful biomarkers of oral infections including apical periodontitis—a putative risk factor for systemic diseases.

Development of guidelines for improving oral health in individuals with Parkinson's disease.

The purpose of this project was to develop evidence-based clinical practice guidelines (CPGs) for the management of oral health (OH) for patients with Parkinson's disease (PD). Individuals with PD have significantly poorer OH than the general population. Poor OH is a risk factor for systemic diseases, including cardiovascular disease, diabetes, and respiratory infections. After an extensive literature review was completed, available evidence was evaluated for inclusion in the initial draft of the guidelines. The draft was then reviewed for content validity by experts in the areas of dentistry, dental hygiene and neurology using the Delphi method. After consensus among the content experts, final guidelines were completed. The final CPG was presented to individuals with PD and their caregivers at a support group. Participants were asked to review the information in the guidelines for 2weeks and then submit a survey regarding the usefulness of the CPG. The CPG was also evaluated by practicing nurse practitioners (NPs) and dental hygienists using the AGREE II tool. Twenty people from the PD support group participated in the educational intervention, and surveys were received from 14 participants. Overall, participants agreed or strongly agreed with each statement related to the applicability and usefulness of the guidelines. The CPG was evaluated using the AGREE II tool, and scores were >80% in all domains with an overall score of 97.1%. Development of these guidelines represent an initial step in improving the oral health and overall health of individuals with PD.

The correlation between pancreatic dysfunction markers and selected indices of periodontitis.

Periodontitis is a major risk factor of systemic diseases with inflammatory etiology. Numerous studies have established the connection between periodontal condition and diabetes, but there are no reports in the literature on the relationship between periodontitis and other pancreas conditions. The activity of pancreatic enzymes is an important parameter of pancreatic damage, and is also a diagnostic marker of acute and chronic pancreatitis, and the bleeding index determines the periodontitis activity. To date, the periodontal status in both of the above-mentioned conditions has not been examined. The objective of the study was to provide a clinical evaluation of oral cavity hygiene and the condition of periodontal tissues in patients diagnosed with pancreatic adenocarcinoma or chronic pancreatitis and in the control group, and to assess the correlation between the activity of periodontitis and the concentration of glycated hemoglobin HbA1c, lipase activity and pancreatic amylase in serum from the examined groups. The serum activity levels of amylase, lipase and HbA1c concentration were correlated with periodontitis activity markers in patients diagnosed with chronic pancreatitis (n = 41), pancreatic cancer (n = 29) and in the control group (n = 50). In the group with chronic pancreatitis, we have found a positive association between the bleeding on probing (BOP) and the amylase activity (r = 0.64) as well as the lipase (r = 0.62; p < 0.05). The patients diagnosed with pancreatic cancer evinced a higher value of the inflammatory response index, namely 1.51, than the other studied groups (H = 24.94; p = 0.01). Patients diagnosed with chronic pancreatitis evinced the highest periodontitis activity indices: BOP: 62.53% (H = 61.31; p = 0.01) and probing depth (PD): 4.14 ±0.89 mm (H = 22.43; p < 0.0001). The study showed that periodontitis in patients with pancreatic cancer is independent of the state of oral hygiene. In the group of patients with chronic pancreatitis, the observed positive correlation between the bleeding index and the enzyme activity suggests interaction between the examined diseases.