Are COVID-19 Polymorphisms in ACE and ACE2 Prognosis Predictors?

Regardless of the containment of the SARS-CoV-2 pandemic, it remains paramount to comprehensively understand its underlying mechanisms to mitigate potential future health and economic impacts, comparable to those experienced throughout the course of the pandemic. The angiotensin-converting enzyme 2 (ACE2) provides anchorage for SARS-CoV-2 binding, thus implicating that ACE and ACE2 might contribute to the variability in infection severity. This study aimed to elucidate predisposing factors influencing the disease course among people infected by SARS-CoV-2, focusing on angiotensin-converting enzyme (ACE) and ACE2 polymorphisms. Notably, despite similar demographics and comorbidities, COVID-19 patients exhibit substantial differences in prognosis. Genetic polymorphisms in ACE and ACE2 have been implicated in disease progression, prompting our investigation into their role in COVID-19 evolution. Using next-generation sequencing (NGS), we analyzed ACE and ACE2 genes in a sample group comprising six subjects infected by SARS-CoV-2. Our findings revealed a correlation between specific polymorphisms and COVID-19 outcomes. Specifically, ACE and ACE2 intronic deletions were observed in all deceased patients, suggesting a potential association with mortality. These results highlight the significance of genetic factors in shaping the clinical course of COVID-19, emphasizing the importance of further research into the impact of genetic variations on COVID-19 severity.

Evaluation of the effects of the Zika Virus-Immunoglobulin G+ complex on murine microglial cells.

After the Zika virus (ZIKV) epidemic in Brazil, ZIKV infections were linked to damage to the central nervous system (CNS) and congenital anomalies. Due to the virus's ability to cross the placenta and reach brain tissue, its effects become severe, leading to Congenital Zika Syndrome (CZS) and resulting in neuroinflammation, microglial activation, and secretion of neurotoxic factors. The presence of ZIKV triggers an inadequate fetal immune response, as the fetus only has the protection of maternal antibodies of the Immunoglobulin G (IgG) class, which are the only antibodies capable of crossing the placenta. Because of limited understanding regarding the long term consequences of ZIKV infection and the involvement of maternal antibodies, this study sought to assess the impact of the ZIKV + IgG⁺complex on murine microglial cells. The cells were exposed to ZIKV, IgG antibodies, and the ZIKV + IgG⁺complex for 24 and 72 h. Treatment-induced cytotoxic effects were evaluated using the cell viability assay, oxidative stress, and mitochondrial membrane potential. The findings indicated that IgG antibodies exhibit cytotoxic effects on microglia, whether alone or in the presence of ZIKV, leading to compromised cell viability, disrupted mitochondrial membrane potential, and heightened oxidative damage. Our conclusion is that IgG antibodies exert detrimental effects on microglia, triggering their activation and potentially disrupting the creation of a neurotoxic environment. Moreover, the presence of antibodies may correlate with an elevated risk of ZIKV-induced neuroinflammation, contributing to long-term CNS damage.

Non-Cytotoxic Graphene Nanoplatelets Upregulate Cell Proliferation and Self-Renewal Genes of Mesenchymal Stem Cells.

Graphene nanoplatelets (UGZ-1004) are emerging as a promising biomaterial in regenerative medicine. This study comprehensively evaluates UGZ-1004, focusing on its physical properties, cytotoxicity, intracellular interactions, and, notably, its effects on mesenchymal stem cells (MSCs). UGZ-1004 was characterized by lateral dimensions and layer counts consistent with ISO standards and demonstrated a high carbon purity of 0.08%. Cytotoxicity assessments revealed that UGZ-1004 is non-toxic to various cell lines, including 3T3 fibroblasts, VERO kidney epithelial cells, BV-2 microglia, and MSCs, in accordance with ISO 10993-5:2020/2023 guidelines. The study focused on MSCs and revealed that UGZ-1004 supports their gene expression alterations related to self-renewal and proliferation. MSCs exposed to UGZ-1004 maintained their characteristic surface markers. Importantly, UGZ-1004 promoted significant upregulation of genes crucial for cell cycle regulation and DNA repair, such as CDK1, CDK2, and MDM2. This gene expression profile suggests that UGZ-1004 can enhance MSC self-renewal capabilities, ensuring robust cellular function and longevity. Moreover, UGZ-1004 exposure led to the downregulation of genes associated with tumor development, including CCND1 and TFDP1, mitigating potential tumorigenic risks. These findings underscore the potential of UGZ-1004 to not only bolster MSC proliferation but also enhance their self-renewal processes, which are critical for effective regenerative therapies. The study highlights the need for continued research into the long-term impacts of graphene nanoplatelets and their application in MSC-based regenerative medicine.

Case Report: Molecular Analyses of Cell-Cycle-Related Genes in Cortical Brain Tissue of a Patient with Rasmussen Encephalitis.

Rasmussen's encephalitis (RE) stands as a rare neurological disorder marked by progressive cerebral hemiatrophy and epilepsy resistant to medical treatment. Despite extensive study, the primary cause of RE remains elusive, while its histopathological features encompass cortical inflammation, neuronal degeneration, and gliosis. The underlying molecular mechanisms driving disease progression remain largely unexplored. In this case study, we present a patient with RE who underwent hemispherotomy and has remained seizure-free for over six months, experiencing gradual motor improvement. Furthermore, we conducted molecular analysis on the excised brain tissue, unveiling a decrease in the expression of cell-cycle-associated genes coupled with elevated levels of BDNF and TNF-α proteins. These findings suggest the potential involvement of cell cycle regulators in the progression of RE.

Neurospheres: a potential in vitro model for the study of central nervous system disorders.

Neurogenesis was believed to end after the period of embryonic development. However, the possibility of obtaining an expressive number of cells with functional neuronal characteristics implied a great advance in experimental research. New techniques have emerged to demonstrate that the birth of new neurons continues to occur in the adult brain. Two main rich sources of these cells are the subventricular zone (SVZ) and the subgranular zone of the hippocampal dentate gyrus (SGZ) where adult neural stem cells (aNSCs) have the ability to proliferate and differentiate into mature cell lines. The cultivation of neurospheres is a method to isolate, maintain and expand neural stem cells (NSCs) and has been used extensively by several research groups to analyze the biological properties of NSCs and their potential use in injured brains from animal models. Throughout this review, we highlight the areas where this type of cell culture has been applied and the advantages and limitations of using this model in experimental studies for the neurological clinical scenario.

Use of induced pluripotent stem cells (iPSCs) and cerebral organoids in modeling the congenital infection and neuropathogenesis induced by Zika virus.

Infection with Zika virus (ZIKV) was recently demonstrated to be associated with damage to the central nervous system, especially microcephaly and the Guillain-Barré syndrome. This finding had alarmed public health agencies and mobilized institutions around the world to search for more information about the virus, its effects, pathophysiological mechanisms, and potential immunizations and treatments. Given the increasing interest in using iPSCs and cerebral organoids to model the congenital infection and neuropathogenesis induced by ZIKV, the aim of this review was to present an up-to-date summary of the publications on the association of ZIKV with microcephaly, using iPSCs and organoids. According to our review, the number of studies has decreased concomitantly with a decrease in the number of cases. The presence of subclinical lesions at birth, which may eventually present cognitive or behavioral problems in the future, suggests that persistent research efforts on the virus should be undertaken by the global health community till the threat is completely wiped out.

Important advances in Alzheimer's disease from the use of induced pluripotent stem cells.

Among the various types of dementia, Alzheimer's disease (AD) is the most prevalent and is clinically defined as the appearance of progressive deficits in cognition and memory. Considering that AD is a central nervous system disease, getting tissue from the patient to study the disease before death is challenging. The discovery of the technique called induced pluripotent stem cells (iPSCs) allows to reprogram the patient's somatic cells to a pluripotent state by the forced expression of a defined set of transcription factors. Many studies have shown promising results and made important conclusions beyond AD using iPSCs approach. Due to the accumulating knowledge related to this topic and the important advances obtained until now, we review, using PubMed, and present an update of all publications related to AD from the use of iPSCs. The first iPSCs generated for AD were carried out in 2011 by Yahata et al. (PLoS One 6:e25788, 2011) and Yaqi et al. (Hum Mol Genet 20:4530-9, 2011). Like other authors, both authors used iPSCs as a pre-clinical tool for screening therapeutic compounds. This approach is also essential to model AD, testing early toxicity and efficacy, and developing a platform for drug development. Considering that the iPSCs technique is relatively recent, we can consider that the AD field received valuable contributions from iPSCs models, contributing to our understanding and the treatment of this devastating disorder.

MTOR pathway in focal cortical dysplasia type 2: What do we know?

Focal cortical dysplasia (FCD) is the most commonly encountered developmental malformation that causes refractory epilepsy. Focal cortical dysplasia type 2 is one of the most usual neuropathological findings in tissues resected therapeutically from patients with drug-resistant epilepsy. Unlike other types of FCD, it is characterized by laminar disorganization and dysplastic neurons, which compromise the organization of the six histologically known layers in the cortex; the morphology and/or cell location can also be altered. A comprehensive review about the pathogenesis of this disease is important because of the necessity to update the results reported over the past years. Here, we present an updated review through Pubmed about the mammalian target of rapamycin (MTOR) pathway in FCD type 2. A wide variety of aspects was covered in 44 articles related to molecular and cellular biology, including experiments in animal and human models. The first publications appeared in 2004, but there is still a lack of studies specifically for one type of FCD. With the advancement of techniques and greater access to molecular and cellular experiments, such as induced pluripotent stem cells (iPSCs) and organoids, it is believed that the trend is increasing the number of publications contributing to the achievement of new discoveries.

Induced Pluripotent Stem Cells and Organoids in Advancing Neuropathology Research and Therapies.

This review delves into the groundbreaking impact of induced pluripotent stem cells (iPSCs) and three-dimensional organoid models in propelling forward neuropathology research. With a focus on neurodegenerative diseases, neuromotor disorders, and related conditions, iPSCs provide a platform for personalized disease modeling, holding significant potential for regenerative therapy and drug discovery. The adaptability of iPSCs, along with associated methodologies, enables the generation of various types of neural cell differentiations and their integration into three-dimensional organoid models, effectively replicating complex tissue structures in vitro. Key advancements in organoid and iPSC generation protocols, alongside the careful selection of donor cell types, are emphasized as critical steps in harnessing these technologies to mitigate tumorigenic risks and other hurdles. Encouragingly, iPSCs show promising outcomes in regenerative therapies, as evidenced by their successful application in animal models.

Influence of Zika virus on the cytotoxicity, cell adhesion, apoptosis and inflammatory markers of glioblastoma cells.

Glioblastoma (GBM) is one of the most common types of brain tumor in adults. Despite the availability of treatments for this disease, GBM remains one of the most lethal and difficult types of tumors to treat, and thus, a majority of patients die within 2 years of diagnosis. Infection with Zika virus (ZIKV) inhibits cell proliferation and induces apoptosis, particularly in developing neuronal cells, and thus could potentially be considered an alternative for GBM treatment. In the present study, two GBM cell lines (U-138 and U-251) were infected with ZIKV at different multiplicities of infection (0.1, 0.01 and 0.001), and cell viability, migration, adhesion, induction of apoptosis, interleukin levels and CD14/CD73 cell surface marker expression were analyzed. The present study demonstrated that ZIKV infection promoted loss of cell viability and increased apoptosis in U-138 cells, as measured by MTT and triplex assay, respectively. Changes in cell migration, as determined by wound healing assay, were not observed; however, the GBM cell lines exhibited an increase in cell adhesion when compared with non-tumoral cells (Vero). The Luminex immunoassay showed a significant increase in the expression levels of IL-4 specifically in U-251 cells (MOI 0.001) following exposure to ZIKV. There was no significant change in the expression levels of IFN-γ upon ZIKV infection in the cell lines tested. Furthermore, a marked increase in the percentage of cells expressing the CD14 surface marker was observed in both GBM cell lines compared with in Vero cells; and significantly increased CD73 expression was observed particularly in U-251 cells, when compared with uninfected cells. These findings indicate that ZIKV infection could lead to reduced cell viability, elevated CD73 expression, improved cellular adherence, and higher rates of apoptosis in glioblastoma cells. Further studies are required to explore the potential use of ZIKV in the treatment of GBM.

Cytotoxicity of esthetic, metallic, and nickel-free orthodontic brackets: cellular behavior and viability.

INTRODUCTION: In this study, we evaluated the cellular viability of various esthetic, metallic, and nickel-free orthodontic brackets. METHODS: The sample was divided into 11 groups (n = 8): cellular control, negative control, positive control, metallic, polycarbonate, 2 types of monocrystalline ceramic, 3 types of nickel free, and polycrystalline ceramic brackets. Cell culture (NIH/3T3-mice fibroblasts) was added to the plates of 96 wells containing the specimens and incubated in 5% carbon dioxide at 37°C for 24 hours. Cytotoxicity was analyzed qualitatively and quantitatively. Cell growth was analyzed with an inverted light microscope, photomicrographs were obtained, and the results were recorded as response rates based on modifications of the parameters of Stanford according to the size of diffusion halo of toxic substances. Cell viability was analyzed (MTT assay); a microplate reader recorded the cell viability through the mitochondrial activity in a length of 570 nm. The values were statistically analyzed. RESULTS: All tested brackets had higher cytotoxicity values than did the negative control (P <0.05), with the exception Rematitan and Equilibrium (both, Dentaurum, Ispringen, Germany) (P >0.05), suggesting low toxicity effects. The values showed that only polycarbonate brackets were similar (P >0.05) to the positive control, suggesting high toxicity. CONCLUSIONS: The brackets demonstrated different ranges of cytotoxicity; nickel-free brackets had better biocompatibility than the others. On the other hand, polycarbonate brackets were made of a highly cytotoxic material for the cells analyzed.

When to test for COVID-19 using real-time reverse transcriptase polymerase chain reaction: a systematic review.

OBJECTIVES: The aim of this study was to evaluate the time in days between symptom onset and first positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) result for COVID-19. METHODS: This systematic review was conducted in the MEDLINE (PubMed), Embase, and Scopus databases using the following descriptors: "COVID-19", "SARS-CoV-2", "coronavirus", "RT-PCR", "real time PCR", and "diagnosis". RESULTS: The included studies were conducted in 31 different countries and reported on a total of 6831 patients. The median age of the participants was 49.95 years. The three most common symptoms were fever, cough, and dyspnea, which affected 4012 (58.68%), 3192 (46.69%), and 2009 patients (29.38%), respectively. Among the 90 included studies, 13 were prospective cohorts, 15 were retrospective cohorts, 36 were case reports, 20 were case series, and six were cross-sectional studies. The overall mean time between symptom onset and positive test result was 6.72 days. Fourteen articles were analyzed separately for the temporal profile of RT-PCR test results; the best performance was on days 22-24, when 98% of test results were positive. CONCLUSION: These findings corroborate the RT-PCR COVID-19 testing practices of some health units. In addition, the most frequently described symptoms of these patients can be considered the initial symptoms of infection and used in decision-making about RT-PCR testing.

Cytotoxicity assessment of Bio-C Repair Íon+: A new calcium silicate-based cement.

Background. Direct pulp capping is a method designed to preserve the exposed dental pulp. Due to good biological, physical, and mechanical properties, new versions of calcium silicate-based materials have been developed as pulp capping materials. The present study aimed to evaluate the cytotoxic effects of four calcium silicate-based pulp capping materials, of which the Bio-C Repair Íon+ is still in an experimental phase. Methods. Biodentine, MTA Repair HP, Bio-C Repair, and Bio-C Repair Íon+ cements were dispensed in a metallic matrix to produce 125-mm3 specimens, which were immersed in Dulbecco's Modified Eagle Medium (DMEM) to obtain extracts. NIH 3T3 cells were cultured and exposed to the extracts for 24 hours and seven days. Cell viability was assessed by the methyl tetrazolium test (MTT). The mean values for the experimental and control groups (without treatment) were compared by analysis of variance (ANOVA) and post hoc Tukey tests, considering a significance level of 5%. Results. All the tested materials demonstrated a reduction in cell viability (P < 0.05). According to ISO 10993-5: 2009 (E), Bio-C Repair Íon+ exhibited mild and moderate cytotoxicity in the 24- hour and 7-day analyses, respectively. Bio-C Repair and Biodentine showed mild cytotoxicity, and MTA Repair HP exhibited moderate cytotoxicity at both intervals. Conclusion. The highest cell viability was demonstrated by Biodentine, MTA, and Repair HP, in descending order. Bio-C Repair and Bio-C Repair Íon+ showed moderate cytotoxicity, similar to MTA Repair HP in the 7-day analysis.

Case Report: Placental Maternal Vascular Malperfusion Affecting Late Fetal Development and Multiorgan Infection Caused by SARS-CoV-2 in Patient With PAI-1 4G/5G Polymorphism.

Background: Pregnant women are susceptible to the novel coronavirus (SARS-CoV-2), and the consequences for the fetus are still uncertain. Here, we present a case of a pregnant woman with subclinical hypothyroidism and a plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism who was infected with SARS-CoV-2 at the end of the third trimester of pregnancy, with unexpected evolution of death of the newborn 4 days postpartum. Methods: Nested PCR was performed to detect the virus, followed by ssDNA sequencing. Results: Transplacental transmission of SARS-CoV-2 can cause placental inflammation, ischemia, and neonatal viremia, with complications such as preterm labor and damage to the placental barrier in patients with PAI-1 4G/5G polymorphism. Conclusion: We showed a newborn with several damages potentially caused due to the PAI-1 polymorphisms carried by the mother infected with SARS-CoV-2 during pregnancy.

Stem cell-based therapy for COVID-19 and ARDS: a systematic review.

Despite global efforts to establish effective interventions for coronavirus disease 2019 (COVID-19) and its major complications, such as acute respiratory distress syndrome (ARDS), the treatment remains mainly supportive. Hence, identifying an effective and safe therapy for severe COVID-19 is critical for saving lives. A significant number of cell-based therapies have been through clinical investigation. In this study, we performed a systematic review of clinical studies investigating different types of stem cells as treatments for COVID-19 and ARDS to evaluate the safety and potential efficacy of cell therapy. The literature search was performed using PubMed, Embase, and Scopus. Among the 29 studies, there were eight case reports, five Phase I clinical trials, four pilot studies, two Phase II clinical trials, one cohort, and one case series. Among the clinical studies, 21 studies used cell therapy to treat COVID-19, while eight studies investigated cell therapy as a treatment for ARDS. Most of these (75%) used mesenchymal stem cells (MSCs) to treat COVID-19 and ARDS. Findings from the analyzed articles indicate a positive impact of stem cell therapy on crucial immunological and inflammatory processes that lead to lung injury in COVID-19 and ARDS patients. Additionally, among the studies, there were no reported deaths causally linked to cell therapy. In addition to standard care treatments concerning COVID-19 management, there has been supportive evidence towards adjuvant therapies to reduce mortality rates and improve recovery of care treatment. Therefore, MSCs treatment could be considered a potential candidate for adjuvant therapy in moderate-to-severe COVID-19 cases and compassionate use.

Correlation between IL-31 and sCD40L plasma levels in Fingolimod-treated patients with Relapsing-Remitting Multiple Sclerosis (RRMS).

INTRODUCTION: Multiple Sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system (CNS). Currently, several protocols are described for the different phases of MS. In this longitudinal study, we aim to quantify the concentration of plasma cytokines of MS patients treated with Fingolimod alone or after Glatiramer Acetate (GA) or Interferon-beta (IFN-ß), in order to compeer both treatments and describes if it is possible to use them as biomarkers. OBJECTIVE: Compare the two different types of drug treatment and describes possible immune biomarkers in RRMS patients treated with Fingolimod alone or after GA or IFN-ß. MATERIALS AND METHODS: This is a controlled, non-randomized clinical trial. Plasma concentrations of IL-31, sCD40L and nine others cytokines were evaluated in two groups of patients with a one-year follow-up. Group 1 (n = 12): RRMS patients treated with GA or IFN-ß for at least six months before the study who changed therapy to Fingolimod after six months, and Group 2 (n = 12): naïve RRMS patients who started treatment with Fingolimod. We used ANOVA two-way to analyze the cytokines and Spearman coefficient to evaluate the correlation. RESULTS: Although Group 2 started with a greater number of relapses per disease duration, Fingolimod treatment was effective in decreasing this parameter, as well as EDSS over 12 months. However, the treatment with GA or IFN-ß on Group 1 showed a tendency to increase the number of relapses after 6 months of follow-up, which decrease when the therapy was changed to Fingolimod. After the evaluation of 11 cytokines in one year, we found that IL-31 and sCD40L were the biomarkers that demonstrated a more difference when compared to the classical ones, following the clinical pattern over the treatment period. CONCLUSIONS: Our study describes the existence of two promising plasmatic biomarkers (IL-31 and sCD40L), which reduced plasmatic levels in RRMS patients followed the treatment time of Fingolimod, despite that more studies are needed to prove their efficiency.

Analysis of genes involved in cell proliferation, adhesion, and control of apoptosis during embryonic neurogenesis in Induced Pluripotent Stem Cells (iPSCs) from patients with Focal Cortical Dysplasia.

Focal cortical dysplasia (FCD) is a malformation of cortical development which is strongly associated with drug-refractory epilepsy. Certain studies have demonstrated an increase in mTOR signaling in patients with FCD on the basis of observation of phosphorylated molecules. The aim of the present study was to verify the differences in genes involved in cell proliferation, adhesion, and control of apoptosis during embryonic neurogenesis in iPSCs derived from the Focal Cortical Dysplasia. Fibroblasts were obtained from the skin biopsies of patients with FCD (n = 2) and controls (n = 2). iPSCs were generated by exposing the fibroblasts to viral vectors that contained the Yamanaka factors (OCT4, SOX2, KLF4, and c-MYC genes) responsible for promoving cell reprogramation. The fibroblasts and iPSCs were tested during different phases of neurodifferentiation for migration capacity and expression of the genes involved in the PI3K pathway. Fibroblasts of patients with FCD migrated with greater intensity during the first two time points of analyses. iPSCs did not exhibit any difference in cell migration between the groups. Fibroblasts, brain tissue, and iPSCs of the patients with FCD exhibited a significant reduction in the relative expression values of 4EBP-1. During neurodevelopment, the iPSCs from patients with FCD exhibited a reduction in the expression of cIAP-1, cIAP-2, PI3K, ß-Catenin and 4EBP-1 gene. We suggest that the differences observed in the migration potential of adult cells and in the gene expression related to the fundamental processes involved in normal brain development during the neurodifferentiation process might be associated with cortical alteration in the patients with FCD.

Intravenous infusion of bone marrow mononuclear cells promotes functional recovery and improves impaired cognitive function via inhibition of Rho guanine nucleotide triphosphatases and inflammatory signals in a model of chronic epilepsy.

Temporal lobe epilepsy is the most common form of intractable epilepsy in adults. More than 30% of individuals with epilepsy have persistent seizures and have drug-resistant epilepsy. Based on our previous findings, treatment with bone marrow mononuclear cells (BMMC) could interfere with early and chronic phase epilepsy in rats and in clinical settings. In this pilocarpine-induced epilepsy model, animals were randomly assigned to two groups: control (Con) and epileptic pre-treatment (Ep-pre-t). The latter had status epilepticus (SE) induced through pilocarpine intraperitoneal injection. Later, seizure frequency was assessed using a video-monitoring system. Ep-pre-t was further divided into epileptic treated with saline (Ep-Veh) and epileptic treated with BMMC (Ep-BMMC) after an intravenous treatment with BMMC was done on day 22 after SE. Analysis of neurobehavioral parameters revealed that Ep-BMMC had significantly lower frequency of spontaneous recurrent seizures (SRS) in comparison to Ep-pre-t and Ep-Veh groups. Hippocampus-dependent spatial and non-spatial learning and memory were markedly impaired in epileptic rats, a deficit that was robustly recovered by treatment with BMMC. Moreover, long-term potentiation-induced synaptic remodeling present in epileptic rats was restored by BMMC. In addition, BMMC was able to reduce abnormal mossy fiber sprouting in the dentate gyrus. Molecular analysis in hippocampal tissue revealed that BMMC treatment down-regulates the release of inflammatory cytokine tumor necrosis factor-α (TNF-α) and Allograft inflammatory factor-1 (AIF-1) as well as the Rho subfamily of small GTPases [Ras homolog gene family member A (RhoA) and Ras-related C3 botulinum toxin substrate 1 (Rac)]. Collectively, delayed BMMC treatment showed positive effects when intravenously infused into chronic epileptic rats.

Hot air stream reduces cytotoxicity of light-cured calcium hydroxide based cements.

BACKGROUND: The light-cured calcium hydroxide based cements have incomplete polymerization and unconverted monomers can cause pulp cell damage. The aim of this study was to evaluate the influence of a warm and hot air stream on the cytotoxicity of light-cured calcium hydroxide based cements. MATERIAL AND METHODS: The materials Dycal (conventional cement), Biocal, Hidrox-Cal, and Ultra-Blend Plus (light-cured calcium hydroxide cements) were submitted to cytotoxicity analysis after polymerization, without vs. with previous heat treatment with a warm (37°C) and a hot (60°C) air stream. Following polymerization, cements were maintained in culture medium for 24 hours and 7 days, and subjected to the MTT test. Data were analyzed using analysis of variance (ANOVA) followed by post-hoc Student-Newman-Keuls (<0.05). RESULTS: The results indicated significant differences between the materials according to their composition, i.e., light-cured cements treated with a jet of warm air showed similar cytotoxicity levels to those observed for conventional cement, suggesting that they may be considered alternatives in cases requiring pulp-capping treatment. CONCLUSIONS: Application of a hot air stream reduced cytotoxicity of materials tested. Key words:Dental pulp capping, dental cements, calcium hydroxide, cell survival.

Complicações relacionadas ao uso de polimetilmetacrilato na face: Análise de 209 casos / Complications related to the use of polymethyl methacrylate on the face: Analysis of 209 cases

Introdução: O polimetilmetacrilato é um produto de preenchimento permanente. A injeção deste material na face pode levar a complicações. O objetivo deste estudo é determinar em uma série de casos o tempo mediano de ocorrência de complicações, as áreas mais comprometidas, os tipos de complicações e tratamentos mais realizados. Método: Foram estudados 209 casos de pacientes portadores de complicações relacionadas ao uso de polimetilmetacrilato na face que buscaram tratamento entre o período de janeiro de 2000 a junho de 2021. Os dados analisados foram sexo, idade, número de injeções, momento da aplicação, intervalo de tempo até surgir a complicação, tipo de complicação, região comprometida e tratamento realizado. Resultados: A idade média dos pacientes foi de 45 anos (23 a 79 anos). Destes, 172 eram mulheres e 37 homens. O número de aplicações variou de 1 a 5. O tempo mediano de surgimento de complicações foi de 71 meses. As regiões mais comprometidas foram a malar, em 102 pacientes; mandibular, em 100; e zigomática, em 91. Granuloma foi observado em 135 pacientes; edema, em 120; e inflamação, em 78. O tratamento mais realizado foi a injeção de corticoide, em 111 pacientes, seguido de remoção cirúrgica, em 40. Conclusão: Os resultados podem servir como base de conhecimento para uma melhor compreensão das complicações com o uso de polimetilmetacrilato na face.

Introduction: Polymethylmethacrylate is a permanent filler product. Injecting this material into the face can lead to complications. The objective of this study is to determine in a series of cases the median time for complications to occur, the most affected areas, the types of complications, and the treatments most performed. Method: 209 cases of patients with complications related to the use of polymethyl methacrylate on the face who sought treatment between the period of January 2000 and June 2021 were studied. The data analyzed were gender, age, number of injections, moment of application, interval time until the complication arises, type of complication, affected region, and treatment performed. Results: The average age of patients was 45 years (23 to 79 years). Of these, 172 were women and 37 men. The number of applications ranged from 1 to 5. The median time for complications to appear was 71 months. The most affected regions were the malar, in 102 patients; mandibular, in 100; and zygomatic, in 91. Granuloma was observed in 135 patients; edema, in 120; and inflammation, in 78. The most common treatment was corticosteroid injection, in 111 patients, followed by surgical removal, in 40. Conclusion: The results can serve as a knowledge base for a better understanding of complications with the use of polymethylmethacrylate in the face.