Histological evaluation of nonsurgical periodontal treatment with and without the use of sodium hypochlorite / amino acids and cross-linked hyaluronic acid gels in dogs.

OBJECTIVES: To evaluate periodontal wound healing following scaling and root planing (SRP) in conjunction with the application of sodium hypochlorite/amino acids and cross-linked hyaluronic acid (xHyA) gels in dogs. MATERIALS AND METHODS: In four beagle dogs, 2-wall intrabony defects were created and metal strips were placed around the teeth. Clinical parameters were measured 4 weeks after plaque accumulation. The experimental root surfaces were subjected to SRP with either the subgingival application of a sodium hypochlorite/amino acid gel and a xHyA gel (test group) or SRP alone (control group) using a split-mouth design. Clinical parameters were re-evaluated at 6 weeks. The animals were sacrificed at 8 weeks for histological analysis. RESULTS: The test group showed significant improvements in all clinical parameters compared to the control group. Histologically, the test group exhibited statistically significantly greater new bone formation [i.e., length of newly formed bone, new bone area] compared with the control group (p < 0.05). Furthermore, statistically significantly greater formation of new attachment [i.e., linear length of new cementum adjacently to newly formed bone with inserting collagen fibers] and new cementum was detected in the test group compared with the control group at 8 weeks (p < 0.05 and p < 0.01, respectively). CONCLUSION: The adjunctive subgingival application of sodium hypochlorite/amino acid and xHyA gels to SRP offers an innovative novel approach to enhance periodontal wound healing/regeneration. CLINICAL RELEVANCE: The present findings have for the first-time shown histologic evidence for periodontal regeneration in support of this novel treatment modality.

Microbiological Effects of Sodium Hypochlorite/-Amino Acids and Cross-linked Hyaluronic Acid Adjunctive to Non-surgical Periodontal Treatment.

PURPOSE: To investigate the microbiological outcomes obtained with either subgingival debridement (SD) in conjunction with a gel containing sodium hypochlorite and amino acids followed by subsequent application of a cross-linked hyaluronic acid gel (xHyA) gel, or with SD alone. MATERIALS AND METHODS: Forty-eight patients diagnosed with stages II-III (grades A/B) generalised periodontitis were randomly treated with either SD (control) or SD plus adjunctive sodium hypochlorite/amino acids and xHyA gel (test). Subgingival plaque samples were collected from the deepest site per quadrant in each patient at baseline and after 3 and 6 months. Pooled sample analysis was performed using a multiplex polymerase chain reaction (PCR)-based method for the identification of detection frequencies and changes in numbers of the following bacteria: Aggregatibacter actinomycetemcomitans (A.a), Porphyromonas gingivalis (P.g), Tannerella forsythia (T.f), Treponema denticola (T.d), and Prevotella intermedia (P.i). RESULTS: In terms of detection frequency, in the test group, statistically significant reductions were found for P.g, T.f, T.d and P.i (p < 0.05) after 6 months. In the control group, the detection frequencies of all investigated bacterial species at 6 months were comparable to the baseline values (p > 0.05). The comparison of the test and control groups revealed statistically significant differences in detection frequency for P.g (p = 0.034), T.d (p < 0.01) and P.i (p = 0.02) after 6 months, favouring the test group. Regarding reduction in detection frequency scores, at 6 months, statistically significant differences in favour of the test group were observed for all investigated bacterial species: A.a (p = 0.028), P.g (p = 0.028), T.f (p = 0.004), T.d (p <0.001), and P.i (p = 0.003). CONCLUSIONS: The present microbiological results, which are related to short-term outcomes up to 6 months post-treatment, support the adjunctive subgingival application of sodium hypochlorite/amino acids and xHyA to subgingival debridement in the treatment of periodontitis.

Clinical evaluation of sodium hypochlorite/amino acids and cross-linked hyaluronic acid adjunctive to non-surgical periodontal treatment: a randomized controlled clinical trial.

OBJECTIVES: To compare the clinical outcomes obtained with either mechanical subgingival debridement in conjunction with a sodium hypochlorite and amino acids containing gel followed by subsequent application of a cross-linked hyaluronic acid gel (xHyA) gel, or with mechanical debridement alone. MATERIALS AND METHODS: Fourty-eight patients diagnosed with stages II-III (Grades A/B) generalised periodontitis were randomly treated with either scaling and root planing (SRP) (control) or SRP plus adjunctive sodium hypochlorite/amino acid and xHyA gels (test). The primary outcome variable was reduction of probing depth (PD), while changes in clinical attachment level (CAL), bleeding on probing (BOP) and plaque index (PI) were secondary outcomes. The outcomes were assessed at baseline, at 3 and 6 months following therapy. RESULTS: All patients completed the 6 months evaluation. At 6 months, the test group showed statistically significantly better results in terms of mean PD reduction (2.9 ± 0.4 vs 1.8 ± 0.6 mm, p < 0.001). Similarly, mean CAL gain was statistically higher in the test group compared to the control one (test: 2.6 ± 0.5 vs control: 1.6 ± 0.6 mm, p < 0.001). Mean BOP decreased from 81.8 ± 16.2% to 48.9 ± 14.5% in control (p < 0.001) and from 83.2 ± 15.5% to 17.6 ± 11.5% in test (p < 0.001) groups with a statistically significant difference favouring the test group (p < 0.001). Mean PI scores were reduced statistically significantly in both groups (from 38.8 ± 26% to 26.5 ± 20.5% in control (p = 0.039) and from 60.6 ± 10.9% to 12.7 ± 8.9% in test group (p < 0.001)), with a statistically significant difference between the groups (p < 0.001). The number of moderate pockets (4-6 mm) were reduced from 1518 (41.2%) to 803 (22.6%) in the control and from 1803 (48.6%) to 234 (7.7%) in the test group with a statistically significant difference between the groups (p < 0.001), while the number of deep pockets (≥ 7 mm) changed from 277 (7.6%) to 35 (1.0%) in the control and from 298 (8.7%) to 4 (0.1%) in test group (p = 0.003). CONCLUSION: Within their limits the present data indicate that: a) both treatments resulted in statistically significant improvements in all evaluated clinical parameters, and b) the adjunctive subgingival application of sodium hypochlorite/amino acid and xHyA to SRP yielded statistically significantly higher improvements compared to SRP alone. CLINICAL RELEVANCE: The combination of sodium hypochlorite/amino acid and xHyA gels to subgingival mechanical debridement appears to represent a valuable approach to additionally improve the outcomes of non-surgical periodontal treatment. Clinical Trial Registration Number NCT04662216 (ClinicalTrials.gov).

Clinical Evaluation of a Novel Combination of Sodium Hypochlorite/Amino Acid and Cross-linked Hyaluronic Acid Adjunctive to Non-surgical Periodontal Treatment: A Case Series.

PURPOSE: The adjunctive subgingival application of sodium hypochlorite/amino acid and a mixture of natural and cross-linked hyaluronic acid gels (high molecular weight) has been recently proposed as a novel modality to enhance the outcomes of non-surgical periodontal therapy. The aim of this prospective case series was to evaluate the clinical outcomes obtained following the subgingival application of a combination of sodium hypochlorite/amino acid and a mixture of natural and cross-linked hyaluronic acid (high molecular) gels in conjunction with non-surgical periodontal therapy. MATERIAL AND METHODS: Twenty-one systemically healthy, non-smoking patients diagnosed with stage II-III, grade A/B periodontitis underwent full-mouth subgingival debridement (SD) performed with ultrasonic and hand instruments. All sites with probing depths (PD) ≥ 4 mm were treated with additional repeated (i.e., 2-3 times) instillation of sodium hypochlorite/amino acid gel in the periodontal pockets prior to and during SRP. Following mechanical debridement, a mixture of natural and cross-linked hyaluronic acid (high molecular) gel was applied in the pockets. The primary outcome variable was PD reduction; changes in clinical attachment level (CAL) and bleeding on probing (BOP) were the secondary outcomes. The clinical parameters were assessed at baseline, 3 and 6 months after therapy. RESULTS: Compared to baseline, a statistically significant mean reduction of PD values was obtained after 3 and 6 months, amounting to 2.6 ± 0.4 mm, and 2.9 ± 0.4 mm, respectively (p < 0.001). Mean CAL gain measured 2.3 ± 0.5 mm at 3 months and 2.6 ± 0.5 mm at 6 months in comparison to baseline (p < 0.001). Mean reduction of BOP values was 54.9 ± 16.9 % at 3 months and 65.6 ± 16.4 % at 6 months (p < 0.001). The number of moderate pockets (4-5 mm) decreased from 1808 at baseline to 274 at the 6-month evaluation, and the number of deep (≥ 6 mm) pockets dropped from 319 to 3, respectively. CONCLUSION: The combination of sodium hypochlorite/amino acid and a mixture of natural and cross-linked hyaluronic acid (high molecular) adjunctive to subgingival debridement may represent a valuable approach to improve the outcomes of non-surgical periodontal treatment.

Clinical efficacy of single and multiple applications of antimicrobial photodynamic therapy in periodontal maintenance: A systematic review and network meta-analysis.

BACKGROUND: At present the clinical efficacy of single (S) versus multiple (M) applications of antimicrobial photodynamic therapy (aPDT) is controversially discussed. AIM: To systematically evaluate the clinical efficacy of adjunctive S and M applications of aPDT to subgingival debridement (SD) in the treatment of residual periodontal pockets. METHODS: An electronic search was carried out for randomized controlled clinical trials (RCTs) reporting on SD with the adjunctive use of S- or M-aPDT applications. RESULTS: Statistically significantly higher improvement in bleeding on probing (BOP) and probing depth (PD) reduction was found for SD + S-aPDT versus SD, with Mean difference (MD) = -16.8 (95% CI: -30.7 to -2.91; p = 0.02) and 0.4, (95% CI: 0.02 to 0.78, p = 0.04), respectively. Regarding BOP, there was also a statistically significant difference when SD + M-aPDT was compared with SD alone, with a MD of -5.13 (95% CI: -7.20 to -3.07; p < 0.00001). For all parameters, SD + S-aPDT demonstrated the best treatment ranking of probability results, followed by SD + M-aPDT and SD alone. CONCLUSIONS: Within their limits, the present data indicate that in periodontal patients enrolled in maintenance: a) single and multiple adjunctive applications of aPDT following SD resulted in statistically significant BOP reduction compared to SD alone, and b) repeated applications of aPDT did not seem to result in superior outcomes compared to single applications.

The Efficacy of Adjunctive Aids in Periodontal Maintenance Therapy: A Systematic Literature Review and Meta-analysis.

PURPOSE: To evaluate the efficacy of adjunctive aids to scaling and root planing (SRP) on clinical outcomes in treating periodontal patients included in regular periodontal maintenance programs. MATERIALS AND METHODS: The electronic databases MEDLINE (Pubmed), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant articles published up to 1st January, 2020. Randomised controlled clinical trials of SRP with or without the use of adjuncts and published in English were included. A meta-analysis using the random-effects model was performed on the selected qualifying articles. RESULTS: Nineteen studies were included in the systematic review and sixteen in the meta-analysis. The overall effect of adjunctive aids was statistically significant for reduction in probing depth (PD) (0.376 mm, 95% CI [0.144 to 0.609]) and clinical attachment level (CAL) gain (0.207 mm, 95% CI [0.0728 to 0.340]). No statistically significant differences were observed for changes in bleeding on probing (BOP) (p > 0.05). Among the different adjuncts, statistically significant positive effects were demonstrated for adjunctive photodynamic therapy (PD reduction 0.908 mm, 95% CI [0.227 to 1.589] and CAL change (0.457 mm, 95% CI [0.133 to 0.782]) and tetracycline fibers (PD reduction 0.534 mm, 95% CI [0.290 to 0.778] and CAL gain 0.280 mm, 95% CI [0.0391 to 0.521]). CONCLUSIONS: Despite high heterogeneity of the investigated data, based on the findings of a current systematic review, adjunctive aids (in particular, photodynamic therapy and tetracycline fibers) combined with SRP provide statistically significant clinical benefits compared to SRP alone. Due to the large number of included studies with high risk of bias, future studies should be based on adequate methodological procedures to improve the overall quality of reporting and to reduce the risk of bias.

Sodium Hypochlorite as an Adjunct to Nonsurgical Treatment of Periodontitis: A Systematic Review.

PURPOSE: To evaluate effects of the adjunctive subgingival application of sodium hypochlorite on clinical outcome following nonsurgical periodontal treatment. MATERIALS AND METHODS: A search protocol was developed to answer the following focused question: 'in patients with periodontitis, does adjunctive subgingival application of sodium hypochlorite have additional clinical benefits compared to subgingival debridement alone?' Randomised controlled clinical trials (RCTs) published up to January 30, 2020, with at least 6 months of follow-up, in which sodium hypochlorite was used as an adjunct in nonsurgical periodontitis treatment were included. The search was limited to the English language. RESULTS: Out of 355 studies retrieved, the search resulted in two publications that fulfilled the inclusion criteria. The adjunctive application of sodium hypochlorite did not provide additional beneficial effect in terms of changes in the evaluated clinical outcomes (i.e. probing depth values [PDs], clinical attachment level gain [CAL] and bleeding on probing [BOP]) when compared to mechanical instrumentation alone over the 12-month investigation period (p > 0.05). CONCLUSION: The available data have failed to show any additional clinical benefit following the use of sodium hypochlorite in conjunction with nonsurgical periodontal therapy.

High fat diet worsens Alzheimer's disease-related behavioral abnormalities and neuropathology in APP/PS1 mice, but not by synergistically decreasing cerebral blood flow.

Obesity is linked to increased risk for and severity of Alzheimer's disease (AD). Cerebral blood flow (CBF) reductions are an early feature of AD and are also linked to obesity. We recently showed that non-flowing capillaries, caused by adhered neutrophils, contribute to CBF reduction in mouse models of AD. Because obesity could exacerbate the vascular inflammation likely underlying this neutrophil adhesion, we tested links between obesity and AD by feeding APP/PS1 mice a high fat diet (Hfd) and evaluating behavioral, physiological, and pathological changes. We found trends toward poorer memory performance in APP/PS1 mice fed a Hfd, impaired social interactions with either APP/PS1 genotype or a Hfd, and synergistic impairment of sensory-motor function in APP/PS1 mice fed a Hfd. The Hfd led to increases in amyloid-beta monomers and plaques in APP/PS1 mice, as well as increased brain inflammation. These results agree with previous reports showing obesity exacerbates AD-related pathology and symptoms in mice. We used a crowd-sourced, citizen science approach to analyze imaging data to determine the impact of the APP/PS1 genotype and a Hfd on capillary stalling and CBF. Surprisingly, we did not see an increase in the number of non-flowing capillaries or a worsening of the CBF deficit in APP/PS1 mice fed a Hfd as compared to controls, suggesting that capillary stalling is not a mechanistic link between a Hfd and increased severity of AD in mice. Reducing capillary stalling by blocking neutrophil adhesion improved CBF and short-term memory function in APP/PS1 mice, even when fed a Hfd.

Antiseptics as adjuncts to scaling and root planing in the treatment of periodontitis: a systematic literature review.

BACKGROUND: Periodontitis is microbially-associated, host-mediated inflammatory condition that results in loss of periodontal attachment. The goals of periodontal therapy include arresting the disease progression, establishing healthy, stable, maintainable periodontal conditions. A fundamental strategy of treating periodontitis is scaling and root planning (SRP), however its efficacy may be restricted in areas inaccessible for mechanical instrumentation. As periodontitis is infectious in nature, it might be helpful to use additional antimicrobial adjuncts, in order to eliminate or inactivate pathogenic microflora. The aim of this study is to evaluate the current evidence regarding the potential clinical benefits of using additional antiseptics for SRP in nonsurgical periodontal therapy. METHODS: An electronic literature search was conducted in the MEDLINE (Ovid) and Cohrane Central Register of Controlled Trials (CENTRAL) databases for articles published between January 1, 2000 and September 22, 2019. Randomized controlled clinical trials in English that compare the effectiveness of one or more antiseptic agents as adjuncts to SRP with a follow-up of ≥6 months were included. A meta-analysis using the random-effects model was performed on the selected qualifying articles. RESULTS: The search resulted in 12 articles that met the inclusion criteria. Based on the vehicle employed to deliver the antiseptic agent, studies were divided into adjunctive sustained-release antiseptics (gels, chips and varnish) and adjunctive irrigation with antiseptics. The meta-analysis demonstrated significant improvements in probing depth (PD) reduction (p = 0.001), clinical attachment level (CAL) gain (p = 0.001), and bleeding on probing (BOP) values (p = 0.001) following the adjunctive subgingival application of sustained-release antiseptics. Additional subgingival irrigation with antiseptics failed to show significant improvements in PD (p = 0.321), CAL (p = 0.7568), or BOP values (p = 0.3549) over SRP alone. CONCLUSIONS: Adjunctive subgingivally delivered antiseptics with a sustained-release delivery have significant clinical benefits compared to SRP alone.

Multi-dimensional immunoproteomics coupled with in vitro recapitulation of oncogenic NRASQ61R identifies diagnostically relevant autoantibody biomarkers in thyroid neoplasia.

Tumor-associated antigen (TAA)-specific autoantibodies have been widely implicated in cancer diagnosis. However, cancer cell lines that are typically exploited as candidate TAA sources in immunoproteomic studies may fail to accurately represent the autoantigen-ome of lower-grade neoplasms. Here, we established an integrated strategy for the identification of disease-relevant TAAs in thyroid neoplasia, which combined NRASQ61R oncogene expression in non-tumorous thyroid Nthy-ori 3-1 cells with a multi-dimensional proteomic technique DISER that consisted of profiling NRASQ61R-induced proteins using 2-dimensional difference gel electrophoresis (2D-DIGE) coupled with serological proteome analysis (SERPA) of the TAA repertoire of patients with thyroid encapsulated follicular-patterned/RAS-like phenotype (EFP/RLP) tumors. We identified several candidate cell-based (nicotinamide phosphoribosyltransferase NAMPT, glutamate dehydrogenase GLUD1, and glutathione S-transferase omega-1 GSTO1) and autoantibody (fumarate hydratase FH, calponin-3 CNN3, and pyruvate kinase PKM autoantibodies) biomarkers, including NRASQ61R-induced TAA phosphoglycerate kinase 1 PGK1. Meta-profiling of the reactivity of the identified autoantibodies across an independent SERPA series implicated the PKM autoantibody as a histological phenotype-independent biomarker of thyroid malignancy (11/38 (29%) patients with overtly malignant and uncertain malignant potential (UMP) tumors vs 0/22 (p = 0.0046) and 0/20 (p = 0.011) patients with non-invasive EFP/RLP tumors and healthy controls, respectively). PGK1 and CNN3 autoantibodies were identified as EFP/RLP-specific biomarkers, potentially suitable for further discriminating tumors with different malignant potential (PGK1: 7/22 (32%) patients with non-invasive EFP/RLP tumors vs 0/38 (p = 0.00044) and 0/20 (p = 0.0092) patients with other tumors and healthy controls, respectively; СNN3: 9/29 (31%) patients with malignant and borderline EFP/RLP tumors vs 0/31 (p = 0.00068) and 0/20 (p = 0.0067) patients with other tumors and healthy controls, respectively). The combined use of PKM, CNN3, and PGK1 autoantibodies allowed the reclassification of malignant/UMP tumor risk in 19/41 (46%) of EFP/RLP tumor patients. Taken together, we established an experimental pipeline DISER for the concurrent identification of cell-based and TAA biomarkers. The combination of DISER with in vitro oncogene expression allows further targeted identification of oncogene-induced TAAs. Using this integrated approach, we identified candidate autoantibody biomarkers that might be of value for differential diagnostic purposes in thyroid neoplasia.