Dexamethasone turns tumor antigen-presenting cells into tolerogenic dendritic cells with T cell inhibitory functions

BackgroundDendritic cells (DCs) are usually immunogenic, but they are also capable of inducing tolerance under anti-inflammatory conditions. Immunotherapy based on autologous DCs loaded with an allogeneic melanoma cell lysate (TRIMEL/DCs) induces immunological responses and increases melanoma patient survival. Glucocorticoids can suppress DC maturation and function, leading to a DC-mediated inhibition of T cell responses.MethodsThe effect of dexamethasone, a glucocorticoid extensively used in cancer therapies, on TRIMEL/DCs phenotype and immunogenicity was examined.ResultsDexamethasone induced a semi-mature phenotype on TRIMEL/DC with low maturation surface marker expressions, decreased pro-inflammatory cytokine induction (IL-1β and IL-12) and increased release of regulatory cytokines (IL-10 and TGF-β). Dexamethasone-treated TRIMEL/DCs inhibited allogeneic CD4⁺ T cell proliferation and cytokine release (IFNγ, TNF-α and IL-17). Co-culturing melanoma-specific memory tumor-infiltrating lymphocytes with dexamethasone-treated TRIMEL/DC inhibited proliferation and effector T cell activities, including cytokine secretion and anti-melanoma cytotoxicity.ConclusionsThese findings suggest that dexamethasone repressed melanoma cell lysate-mediated DC maturation, generating a potent tolerogenic-like DC phenotype that inhibited melanoma-specific effector T cell activities. These results suggest that dexamethasone-induced immunosuppression may interfere with the clinical efficacy of DC-based melanoma vaccines, and must be taken into account for optimal design of cellular therapy against cancer.     

Preliminary clinical reports of a novel night-guard tooth bleaching technique modified by casein phosphopeptide-amorphous calcium phosphate (CCP-ACP)

Although supervised night-guard bleaching has proved successful for whitening teeth, both mineral loss and tooth sensitivity are still common problems. The present study introduces a novel remineralizer as well as describes the utilization of a possibly low sensitivity supervised night-guard vital tooth bleaching technique. A 22% carbamide peroxide gel was mixed with the casein phosphopeptide-amorphous calcium phosphate-containing MI Paste. The peroxide/MI Paste mixture was prepared with 1 ml of each material until obtaining a homogeneous paste. Five patients were instructed to follow a home bleaching protocol for 3 weeks. The outcome was assessed visually with a Vitapan scale. All subjects presented reduction of at least two Vitapan scale units after bleaching and no sensitivity was reported. The concomitant use of MI Paste and peroxide might not affect the gel effectiveness and still reduce hypersensitivity levels.     

Diclofenac in hyaluronic acid gel: an alternative treatment for actinic cheilitis

Objective

Actinic cheilitis (AC) is a precancerous lesion of the lip vermillion caused by prolonged exposure to ultraviolet light. The aim of this study was to evaluate the effect of 3% diclofenac in 2.5% hyaluronic acid gel in the treatment of AC.

Methods

Thirty-four patients with chronic AC were treated twice a day with topical diclofenac during a period of 30 to 180 days. The individuals were followed up every 15 days by means of clinical examination and digital photographic documentation.

Results

Of the 27 patients that completed the study, 12 (44%) showed complete remission of the whitish plaques and exfoliative areas, and 15 (56%) had partial remission of the clinical picture of cheilitis. The latter group was submitted to excision of the leukoplakic areas which diagnosis varied from mild to moderate epithelial dysplasia.

Conclusion

The results suggest a promising role for diclofenac in hyaluronic acid gel in the treatment of AC. This treatment has the advantages of not being invasive and showing few side effects.     

Impact of oral health on quality of life among the elderly population of Joaçaba, Santa Catarina, Brazil

The objective of this study was to investigate the impact of oral health conditions on the quality of life of elderly people in Joa?aba - SC, in Southern Brazil. A survey based on systematic sampling of clusters was carried out with 183 elderly people that belong to old age groups. The survey was conducted in order to assess the oral conditions of the participants (use of and need for prosthesis) based on the criteria from the World Health Organization publication "Oral Health Surveys, Basic Methods", 4th edition. The oral health impact profile (OHIP) was used to evaluate the impact of oral condition in the quality of life. ABIPEME (Brazilian Association of Market Research Institutes) criterion was used, together with the level of education and the number of people in the household to determine social inequalities. The participants were mostly women (82%) and the OHIP mean was 10.35. No correlation was observed between the OHIP level and formal education or between OHIP and number of residents per household. There was a correlation of 0.240 (p = 0.001) between ABIPEME and OHIP. The OHIP mean for those not using maxillary prosthesis was 12.48 and the mean for those using it was 9.81 (p = 0.399). The mean OHIP for those in need of maxillary prosthesis for those who did not need it was 13.00 and 8.88, respectively (p = 0.014). The same trend was found for the use and need for mandibular prosthesis. The conclusion was that the need for maxillary and mandibular prosthesis impacted the quality of life among the elderly population of Joa?aba.     

Effect of the sodium hypochlorite and citric acid association on smear layer removal of primary molars

This study aimed to assess the capacity of a sodium hypochlorite and citric acid (CA) association (the latter at different concentrations) in removing coronal smear layer (SL) of primary teeth. For this purpose, the pulp chamber roof and floor of 28 primary molars were removed to obtain enamel and dentine disks. SL was produced on the internal walls of the disks using high-speed drills. The disks were irrigated with 1% sodium hypochlorite and citric acid at different concentrations (CA-4%, CA-6%, CA-8% and CA-10%), and with 0.9% sodium chloride. The samples were split and observed under SEM. Scores were attributed to the obtained photomicrographs, according to the amount of SL present. It was noted that all the tested concentrations of citric acid used after the sodium hypochlorite were capable of removing SL. The results were analyzed by the Kruskal-Wallis test, and there was no significant statistical difference among the scores of the groups tested. However, it was observed that CA-8% and CA-10% caused peritubular dentine destruction, and that CA-4% presented a larger number of samples with dense SL. Based on these results, 6.0% citric acid in association with 1% sodium hypochlorite is suggested as auxiliary chemical substances for primary teeth irrigation.     

Severe acute respiratory syndrome coronavirus 2 infection in asymptomatic pediatric dental patients

BackgroundChildren with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are typically asymptomatic but contagious. The authors investigated the positivity rate of asymptomatic SARS-CoV-2 infection in pediatric dental patients.MethodsThe authors reviewed consecutive charts of children younger than 18 years scheduled for elective dental procedures from April 1, 2020, through August 1, 2020. All patients were screened for signs and symptoms of SARS-CoV-2 infection. Asymptomatic patients scheduled for dental procedures underwent polymerase chain reaction (PCR) testing for SARS-CoV-2. Sociodemographic characteristics were abstracted, and positivity rates were calculated. Variables for patients who were SARS-CoV-2 positive and SARS-CoV-2 negative were compared using Fisher exact and Mann-Whitney U tests.ResultsThe sample size was 921. The median age was 6 years, and 50.9% were boys. The overall SARS-CoV-2 positivity rate was 2.3%. Age, insurance status, medical history, and dental diagnosis were comparable in patients who were SARS-CoV-2 positive and SARS-CoV-2 negative. Positivity rates were statistically higher for Hispanic or Latinx patients than other groups (P = .038).ConclusionsAlthough the yield of testing was low, the systematic evaluation of asymptomatic pediatric dental cases via PCR resulted in the identification of SARS-CoV-2 carriers who could have been infectious. In this study, Hispanics or Latinx had a higher positivity rate than other demographic groups.Practical ImplicationsPCR testing for SARS-CoV-2 of asymptomatic patients in pediatric dentistry adds value to the use of screening questionnaires for the identification of infected people who could be contagious.     

Do current therapeutic anti-Aβ antibodies for Alzheimer’s disease engage the target?

Reducing amyloid-β peptide (Aβ) burden at the pre-symptomatic stages of Alzheimer’s disease (AD) is currently the advocated clinical strategy for treating this disease. The most developed method for targeting Aβ is the use of monoclonal antibodies including bapineuzumab, solanezumab and crenezumab. We have synthesized these antibodies and used surface plasmon resonance (SPR) and mass spectrometry to characterize and compare the ability of these antibodies to target Aβ in transgenic mouse tissue as well as human AD tissue. SPR analysis showed that the antibodies were able to bind Aβ with high affinity. All of the antibodies were able to bind Aβ in mouse tissue. However, significant differences were observed in human brain tissue. While bapineuzumab was able to capture a variety of N-terminally truncated Aβ species, the Aβ detected using solanezumab was barely above detection limits while crenezumab did not detect any Aβ. None of the antibodies were able to detect any Aβ species in human blood. Immunoprecipitation experiments using plasma from AD subjects showed that both solanezumab and crenezumab have extensive cross-reactivity with non-Aβ related proteins. Bapineuzumab demonstrated target engagement with brain Aβ, consistent with published clinical data. Solanezumab and crenezumab did not, most likely as a result of a lack of specificity due to cross-reactivity with other proteins containing epitope overlap. This lack of target engagement raises questions as to whether solanezumab and crenezumab are suitable drug candidates for the preventative clinical trials for AD.     

Topical 5‐azacytidine accelerates skin wound healing in rats

The development of new methods to improve skin wound healing may affect the outcomes of a number of medical conditions. Here, we evaluate the molecular and clinical effects of topical 5‐azacytidine on wound healing in rats. 5‐Azacytidine decreases the expression of follistatin‐1, which negatively regulates activins. Activins, in turn, promote cell growth in different tissues, including the skin. Eight‐week‐old male Wistar rats were submitted to 8.0‐mm punch‐wounding in the dorsal region. After 3 days, rats were randomly assigned to receive either a control treatment or the topical application of a solution containing 5‐azacytidine (10 mM) once per day. Photo documentation and sample collection were performed on days 5, 9, and 15. Overall, 5‐azacytidine promoted a significant acceleration of complete wound healing (99.7% ± 0.7.0 vs. 71.2% ± 2.8 on day 15; n = 10; p < 0.01), accompanied by up to threefold reduction in follistatin expression. Histological examination of the skin revealed efficient reepithelization and cell proliferation, as evaluated by the BrdU incorporation method. 5‐Azacytidine treatment also resulted in increased gene expression of transforming growth factor‐beta and the keratinocyte markers involucrin and cytokeratin, as well as decreased expression of cytokines such as tumor necrosis factor‐alpha and interleukin‐10. Lastly, when recombinant follistatin was applied to the skin in parallel with topical 5‐azacytidine, most of the beneficial effects of the drug were lost. Thus, 5‐azacytidine acts, at least in part through the follistatin/activin pathway, to improve skin wound healing in rodents.     

Effects of laser irradiation (670-nm InGaP and 830-nm GaAlAs) on burn of second-degree in rats

This study investigated the effects of 670-nm indium gallium phosphide (InGaP) and 830-nm gallium aluminum arsenide (GaAlAs) laser therapy on second-degree burns induced on the back of Wistar rats. Sixty-three male Wistar rats were anesthetized, and second-degree burns were made on their back. The animals were then divided randomly into three groups: control (C), animals treated with 670-nm InGaP laser (LIn), and animals treated with 830-nm GaAlAs laser (LGa). The wound areas were removed after 2, 6, 10, 14, and 18 days of treatment and submitted to structural and morphometric analysis. The following parameters were studied: total number of granulocytes and fibroblasts, number of newly formed blood vessels, and percentage of birefringent collagen fibers in the repair area. Morphometric analysis showed that different lasers 670-nm InGaP and 830-nm GaAlAs reduced the number of granulocytes and an increase of newly formed vessels in radiated lesions. The 670-nm InGaP laser therapy was more effective in increasing the number of fibroblasts. The different treatments modified the expression of VEGF and TGF-β1, when compared with lesions not irradiated. The different types of light sources showed similar effects, improved the healing of second-degree burns and can help for treating this type of injury. Despite the large number of studies with LLTI application in second-degree burns, there is still divergence about the best irradiation parameters to be used. Further studies are needed for developing a protocol effective in treating this type of injury.