Silveira GR, et al. J Periodontal Implant Sci. 2021 Sep;51:e37. https://doi.org/10.5051/jpis.2100420021

Objetivo: nesta revisão sistemática, nós avaliamos o link entre indutores de estresse oxidativo e/ou nitrosativo (EO/EN) com atividade antifúngica, através de uma ação direta sobre a célula fúngica e/ou modulando a resposta de fagócitos contra fungos de interesse médico (incluindo Candida spp., Cryptococcus spp. e Aspergillusspp.). Ainda, foram avaliadas as implicações clínicas deste evento bioquímico, bem como as perspectivas quanto à busca por novos compostos com atividade antifúngica, principalmente, os provenientes de fonte natural e, que explorem a indução de um EO ou EN como parte de seu mecanismo de ação. Metodologia: foram avaliados artigos, provenientes de diferentes bases de dados e publicados a qualquer período, acessados entre abril e junho de 2017, através da utilização de diferentes descritores. Resultados: primeiramente, estabelecemos as definições de EO/EN, como sendo aumento das concentrações de espécies reativas do oxigênio e/ou nitrogênio (ERO/ERN) quantificado diretamente e, provenientes de fontes fúngicas mitocondriais, Reação de Fenton, retículo endoplasmático ou outras não definidas, e excedendo a capacidade de defesa antioxidante do microrganismo (avaliados por análises de perfis transcriptômicos ou proteômicos ou metabolômicos ou níveis de atividade enzimática). Este aumento de ERO/ERN causando EO/EN é definido por tempo e condições que conduzem a sinalização de apoptose ou reais danos a biomoléculas com perda de função (peroxidação lipídica ou oxidação proteica ou danos ao DNA) e, consequentemente, gerando morte fúngica ou outro efeito antifúngico associado. Portanto, 64 artigos (apenas um publicado antes do ano 2000 e 50 entre 2007-2017) abordam que a indução de EO ou EN na célula fúngica é parte do mecanismo de ação de clássicos agentes antifúngicos (22 publicações), tais como azóis (fluconazol, itraconazol e miconazol), polienos (anfotericina B [AnB]) e equinocandinas (mica-fungina), assim como tal modulação redox tem sido reportada como um importante alvo terapêutico na busca por novos e promissores compostos naturais com atividade antifúngica (32 publicações), que tem respaldo pela grande variedade de indutores que podem provir da natureza. Ainda, compostos que também induzem o burstoxidativo de fagócitos, incluindo AnB, são potencializadores do efeito antifúngico in vivo. Além do efeito antifúngico contra células planctônicas, os efeitos dos EO ou EN sobre biofilmes fúngicos, também têm sido reportados. Tem sido firmado na literatura recente um claro link entre EO ou EN e a atividade antifúngica, tanto para aqueles agentes antifúngicos já utilizados na terapêutica em humanos, quanto para possíveis candidatos a fármaco. Portanto, a indução do EO ou EN como parte do mecanismo de ação de antifúngicos demonstra ser um importante alvo terapêutico, com perspectivas favoráveis sobre os desfechos na prática clínica. Aim:In this systematic review, we evaluated the link between inducers of oxidative or nitrosative stresses (OS/NS) and antifungal activity against fungi of medical relevance (including Candida spp., Cryptococcus spp., and Aspergillus spp.), through a direct action on the fungal cell or modulating phagocyte response. Moreover, the clinical implications of this biochemical event, as well as the perspectives, were examined, highlighting the search for new compounds with antifungal activity, mainly those from natural sources and, which explores the induction of OS or NS as part of the mechanism of action. Methodology:Articles from different data-bases and published at any time were evaluated, between April and June 2017, and using different descriptors. Results:First, a definition of OS and NS was established in which an increase in reactive oxygen or nitrogen species (ROS/RNS, quantified directly and from mitochondrial, Fenton reaction, endoplasmic reticulum or other fungal sources) should exceed the antioxidant defense capacity of the microorganism (evaluated by transcriptomic or proteomic or metabolomic profiles or enzyme activity levels). These events, by time and conditions delimited, can lead to the signaling of apoptosis or an actual damage toward biomolecules (lipid peroxidation or protein oxidation or DNA damage) and, consequently, they can cause cell death or other associated antifungal effect. Therefore, 64 articles were found, of these, only one was published before 2000 and 50 between 2007-2017, reporting the induction of OS or NS directly into the fungal cell via an increase in ROS or RNS as part of the mechanism of action of classical antifungal agents (22 publications), such as: azoles (fluconazole, itraconazole, and micon-azole), polyenes (amphotericin B, [AnB]), and echinocandins (micafungin). This redox modulation has also been reported as an important therapeutic target in the search for new natural compounds with antifungal activity (32 publications), which is supported for the great variety of inducers from nature. Compounds that also induce the oxidative burst of phagocytes, including AnB, promote a combina-torial antifungal effect in vivo. In addition to the antifungal effect against plank-tonic cells, the relation between OS or NS and antifungal activity against fungal biofilms has also been reported. It has been established in...

Objective: To evaluate the pulp tissue of rat molars after pulpotomies with mineral trioxide aggregate (MTA), BiodentineTM (BDT) and calcium hydroxide (CH) mixed with sterile saline solution (24 hours, 72 hours, 7 days and 15 days), through correlating MPO activity with active neutrophils and MMP8 activity with tissue remodeling. Material and Methods: Thirty-eight Wistar rats were randomly distributed into groups (control, I (MTA gray), II (BDT), and III (CH)) and subdivided according to the study period of 24 hours, 72 hours, 7 days or 15 days after pulpotomy. MMP8 activity was assessed through fluorescence technique, and MPO activity was determined using the MPO assay. Results: A gradual decrease of MPO and MM8 activity occurred in the group MTA over the experimental periods (p<0.05). Groups BDT and CH exhibited an increase in the activity at 7 and 15 days (p<0.05). Conclusion: MTA demonstrated a decrease in the values of MPO e MMP8. BDT and CH showed high neutrophilic and collagenase activity over the experimental periods.

Secondary disorders in consequences to diabetes involves the development of several diseases in the oral cavity, as periodontitis, xerostomy, infection by diverse pathogens and dysfunctions on the salivary secretion. These alterations occur partially, in consequence of the oxidative stress occasioned by hyperglycemia, and are important in patients undiagnosed or that have flaws in their therapeutic process. The aim of this work was to evaluate biochemical alterations of submandibular glands in response to oxidative stress during diabetes mellitus, and verify the effects of N-acetylcystein supplementation to diabetic rats, specially on the regulation of modifications related to glutathione and thiol proteins. For this purpose, the levels of some oxidative stress markers and the occurrence of the post-translational event of S-glutathionylation were evaluated. The a-amilase degranulation by isolated acinar cells and glandular relative weight was also measured for each experimental group. The compound was able to decrease the lipoperoxidation and proteic oxidation observed in the submandibular gland of diabetic rats, preventing the decrease of the tecidual reducing power and increasing the occurrence of the post-translational process of S-glutathionylation. The diabetic condition increases the degranulation of a-amilase and the glandular weight, but the supplementation with N-acetylcystein did not affect these events. Together these findings may help to elucidate the status of oxidative stress on salivary glands and suggest new therapeutic strategies employing antioxidants of low molecular weight to prevent oral and systemic dysfunctions related to diabetes.

Background/Objectives: Safe discharge after neurosurgical traumatic brain injury (TBI) depends on documented counseling and appropriate referrals, yet real-world fidelity is uncertain in resource-constrained settings. We quantified discharge process quality and identified digitally actionable gaps. Methods: The sample for this study was a retrospective cohort of 559 consecutive neurosurgical TBI patients discharged from a Brazilian public tertiary center (2012–2022). Data were abstracted from electronic health records. The primary outcome was documentation of warning sign counseling at discharge. Proportions are reported with exact Clopper–Pearson 95% confidence intervals. Results: The median age was 66 years (IQR 47–79.5); 78.5% were male and most received care under the public health system. Subdural hematoma predominated; hematoma drainage was the most frequent procedure. Warning sign counseling was documented in 16.1% of cases (89/559; 95% CI 13.2–19.5), and no palliative care referrals were recorded. Conclusions: A low baseline for a safety-critical discharge element exposes an immediately actionable target. Embedding discharge order sets with mandatory counseling fields in the EHR, clinical decision support prompts for palliative care screening and follow-up, and QR-coded patient handouts represent a pragmatic path to improve discharge quality and end-of-life readiness in the digital era.