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1.
Braz J Biol ; 84: e280240, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38695422

RESUMO

Transporting live fish is a common practice in fish farming, and is certainly one of the main problems that affect fish homeostasis. In this scenario, the use of natural additives has shown promise in improving fish resistance to adverse situations. This study aimed to assess the impact of Ocimum gratissimum L. essential oil (OGEO) on water quality, hematological parameters, and residue levels in the plasma, fillet, and liver of juvenile piraputanga (Brycon hilarii) during a two-hour transportation period. The fish were divided into plastic bags (4 L) and exposed to three different OGEO concentrations (10, 20, and 30 mg L-1), while a control group received no OGEO (three repetitions each). After the two-hour transportation, blood samples were collected, as well as portions of the fillet and liver for quantifying essential oil compounds, which were also measured in the plasma. Oxygen levels remained high throughout the transportation period, in all groups, while the pH decreased. Hemoglobin, MCHC, and MCH increased in fish exposed to OGEO concentrations of 20 and 30 mg L-1, compared to the control group. However, lymphocyte counts and the concentrations of essential oil compounds in plasma, fillet, and liver increased with higher OGEO concentrations. The use of 10 mg L-1 OGEO in the two-hour transport water is promising to ensure the survival and well-being of Brycon hilarii juveniles (weighing 16 g), showing to be safe and effective. The residual concentration of eugenol the major compound of OGEO in the fillet remains below the maximum limit of the recommended daily intake.


Assuntos
Fígado , Ocimum , Óleos Voláteis , Qualidade da Água , Animais , Ocimum/química , Óleos Voláteis/química , Fígado/química , Fígado/efeitos dos fármacos , Meios de Transporte , Caraciformes/sangue , Poluentes Químicos da Água/análise
2.
J Endocrinol Invest ; 47(1): 141-147, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37306894

RESUMO

PURPOSE: Sexual dysfunctions are often experienced by male patients with acromegaly, due to a combination of hypogonadism and other comorbidities, but are a scarcely investigated complication. Erectile dysfunction is also closely related to cardiovascular diseases through endothelial dysfunction. Therefore, this project aimed to assess the prevalence of erectile dysfunction in a population of acromegalic men and evaluate its association with cardio-metabolic disorders, also exploring associations with androgen and estrogen receptor gene polymorphisms. METHODS: Sexually active men aged 18-65 with previous diagnosis of acromegaly were recruited. Clinical and laboratory data were retrospectively collected. Each patient also provided a blood sample for AR and ERß gene polymorphisms analyses and filled out the IIEF-15 questionnaire. RESULTS: Twenty men with previous diagnosis of acromegaly (mean age 48.4 ± 10.0 years) were recruited. 13/20 subjects (65%) had erectile dysfunction, but only four had a concurrent biochemical hypogonadism, with no significant correlation with IIEF-15 scores. Total testosterone negatively correlated with sexual intercourse satisfaction domain (ρ = - 0.595; p = 0.019) and general satisfaction domain (ρ = - 0.651; p = 0.009). IGF-1 levels negatively correlated with biochemical hypogonadism (ρ = - 0.585; p = 0.028). The number of CAG and CA repeats in AR and ERß receptors genes was not significantly associated with IIEF-15 scores or with GH/IGF-1 levels, but a negative correlation between CA repeats and the presence of cardiomyopathy (ρ = - 0.846; p = 0.002) was present. CONCLUSIONS: Men with acromegaly have a high prevalence of erectile dysfunction, but it does not appear to be correlated with treatments, testosterone levels and AR/ER-beta signaling. Nonetheless, a shorter CA polymorphic trait (ERbeta) is associated with the presence of cardiomyopathy. If confirmed, these data may suggest an association between an incorrect hormonal balance and increased cardiovascular risk in acromegaly subjects.


Assuntos
Acromegalia , Cardiomiopatias , Disfunção Erétil , Hipogonadismo , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Androgênios , Disfunção Erétil/epidemiologia , Disfunção Erétil/genética , Acromegalia/complicações , Acromegalia/genética , Fator de Crescimento Insulin-Like I/genética , Estudos Retrospectivos , Receptor beta de Estrogênio/genética , Testosterona , Hipogonadismo/complicações , Hipogonadismo/epidemiologia , Hipogonadismo/genética , Polimorfismo Genético , Estrogênios
3.
ESMO Open ; 8(2): 101160, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36871392

RESUMO

BACKGROUND: Acquired resistance limits long-term epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) efficacy in patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) in whom anti-programmed death-ligand 1 (PD-L1) efficacy is also limited. We hypothesized that combining atezolizumab with erlotinib could enhance antitumor immunity and extend efficacy in these patients. PATIENTS AND METHODS: This open-label phase Ib trial was conducted in adults aged ≥18 years who had advanced, unresectable NSCLC. Stage 1 (safety evaluation) enrolled EGFR TKI-naive patients regardless of EGFR status. Stage 2 (expansion) enrolled patients with EGFR-mutant NSCLC treated with ≤1 prior non-EGFR TKI therapy. Patients received 150 mg erlotinib orally once daily. After a 7-day erlotinib run-in, atezolizumab 1200 mg was administered intravenously every 3 weeks. The primary endpoint was the safety and tolerability of the combination in all patients; secondary endpoints included antitumor activity per RECIST 1.1 in stage 2 patients. RESULTS: At the data cut-off on 7 May 2020, 28 patients (8 in stage 1, 20 in stage 2) were assessable for safety. No dose-limiting toxicities or grade 4 or 5 treatment-related adverse events occurred. Grade 3 treatment-related adverse events occurred in 46% of patients; the most common were increased alanine aminotransferase, diarrhea, pyrexia, and rash (each in 7% of patients). Serious adverse events occurred in 50% of patients. Pneumonitis (grade 1) was reported in a single patient (4%). The objective response rate was 75% [95% confidence interval (CI) 50.9% to 91.3%]), median response duration was 18.9 months (95% CI 9.5-40.5 months), median progression-free survival was 15.4 months (95% CI 8.4-39.0 months), and median overall survival was not estimable (NE) (95% CI 34.6-NE). CONCLUSIONS: Atezolizumab combined with erlotinib demonstrated a tolerable safety profile and encouraging, durable clinical activity in patients with advanced EGFR mutation-positive NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adulto , Humanos , Adolescente , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Cloridrato de Erlotinib/efeitos adversos , Neoplasias Pulmonares/patologia , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico
4.
Arch Soc Esp Oftalmol (Engl Ed) ; 98(3): 170-174, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36738920

RESUMO

Descemet Membrane detachment is a potential complication after Descemet Membrane Endothelial Keratoplasty (DMEK). Here, we present a unique case of a DMEK surgery in a complicated eye that suffered a nearly complete DMEK graft detachment and later a graft opacification with a pseudo-anterior chamber. In Mid-November 2020, a planned DMEK was performed in a 64-year-old male patient due to corneal decompensation. Four months after DMEK, a fibrotic DMEK graft was seen across the anterior chamber with a pseudo-anterior chamber; however, the recipient cornea showed complete clearance with an endothelial cell count of about 1204 cells/mm2 and a best-corrected visual acuity of 20/25. Three months later, we observed a significant opacification of the detached graft, and the best-corrected distance visual acuity decreased to 20/63. We proceeded with the graft removal without performing a second DMEK. Ten months after graft removal, the cornea remained clear with an endothelial cell count of about 510 cells/mm2, and the best-corrected visual acuity was 20/25.


Assuntos
Doenças da Córnea , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Masculino , Humanos , Pessoa de Meia-Idade , Endotélio Corneano , Acuidade Visual , Córnea , Doenças da Córnea/cirurgia
5.
ESMO Open ; 8(1): 100747, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36563519

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is associated with poor prognosis, and new treatment options are urgently needed. About 34%-39% of primary TNBCs show a low expression of human epidermal growth factor receptor 2 (HER2-low), which is a target for new anti-HER2 drugs. However, little is known about the frequency and the prognostic value of HER2-low in metastatic TNBC. PATIENTS AND METHODS: We retrospectively included patients with TNBC from five European countries for this international, multicenter analysis. Triple-negativity had to be shown in a metastatic site or in the primary breast tumor diagnosed simultaneously or within 3 years before metastatic disease. HER2-low was defined as immunohistochemically (IHC) 1+ or 2+ without ERBB2 gene amplification. Survival probabilities were calculated by the Kaplan-Meier method, and multivariable hazard ratios (HRs) were estimated by Cox regression models. RESULTS: In total, 691 patients, diagnosed between January 2006 and February 2021, were assessable. The incidence of HER2-low was 32.0% [95% confidence interval (CI) 28.5% to 35.5%], with similar proportions in metastases (n = 265; 29.8%) and primary tumors (n = 425; 33.4%; P = 0.324). The median overall survival (OS) in HER2-low and HER2-0 TNBC was 18.6 and 16.1 months, respectively (HR 1.00; 95% CI 0.83-1.19; P = 0.969). Similarly, in multivariable analysis, HER2-low had no significant impact on OS (HR 0.95; 95% CI 0.79-1.13; P = 0.545). No difference in prognosis was observed between HER2 IHC 0/1+ and IHC 2+ tumors (HR 0.89; 95% CI 0.69-1.17; P = 0.414). CONCLUSIONS: In this large international dataset of metastatic TNBC, the frequency of HER2-low was 32.0%. Neither in univariable nor in multivariable analysis HER2-low showed any influence on OS.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Estudos Retrospectivos , Prognóstico , Europa (Continente)
9.
Sci Rep ; 12(1): 20250, 2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36424421

RESUMO

Glucocorticoids are regularly used as biomarkers of relative health for individuals and populations. Around the Western Antarctic Peninsula (WAP), baleen whales have and continue to experience threats, including commercial harvest, prey limitations and habitat change driven by rapid warming, and increased human presence via ecotourism. Here, we measured demographic variation and differences across the foraging season in blubber cortisol levels of humpback whales (Megaptera novaeangliae) over two years around the WAP. Cortisol concentrations were determined from 305 biopsy samples of unique individuals. We found no significant difference in the cortisol concentration between male and female whales. However, we observed significant differences across demographic groups of females and a significant decrease in the population across the feeding season. We also assessed whether COVID-19-related reductions in tourism in 2021 along the WAP correlated with lower cortisol levels across the population. The decline in vessel presence in 2021 was associated with a significant decrease in humpback whale blubber cortisol concentrations at the population level. Our findings provide critical contextual data on how these hormones vary naturally in a population over time, show direct associations between cortisol levels and human presence, and will enable comparisons among species experiencing different levels of human disturbance.


Assuntos
COVID-19 , Jubarte , Humanos , Animais , Masculino , Feminino , Hidrocortisona , Regiões Antárticas , Estações do Ano
10.
Colloids Surf B Biointerfaces ; 219: 112774, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36067682

RESUMO

Bone healing after a tumor removal can be promoted by biomaterials that enhance the bone regeneration and prevent the tumor relapse. Herein, we obtained several nanopatterns by self-assembly of polystyrene-block-poly-(2-vinylpyridine) (PS-b-P2VP) with different molecular weights and investigated the adhesion and morphology of human bone marrow mesenchymal stem cells (BMMSC) and osteosarcoma cell line (SaOS-2) on these patterns aiming to identify topography and chemistry that promote bone healing. We analyzed > 2000 cells per experimental condition using imaging software and different morphometric descriptors, namely area, perimeter, aspect ratio, circularity, surface/area, and fractal dimension of cellular contour (FDC). The obtained data were used as inputs for principal component analysis, which showed distinct response of BMMSC and SaOS-2 to the surface topography and chemistry. Among the studied substrates, micellar nanopatterns assembled from the copolymer with high molecular weight promote the adhesion and spreading of BMMSC and have an opposite effect on SaOS-2. This nanopattern is thus beneficial for bone regeneration after injury or pathology, e.g. bone fracture or tumor removal.

11.
Artigo em Inglês | MEDLINE | ID: mdl-35760695

RESUMO

Mastocytosis is characterized by clonal expansion of mast cells, with abnormal accumulation in different organs. Perioperatively, numerous stimuli may lead to the release of vasoactive substances by mast cells. Parturients with systemic mastocytosis pose a challenge to the anesthesiologist: on one hand, the pain and stress of labor may lead to greater mast cell activation and, on the other, the administration of drugs that may possibly trigger the release of mast cell mediators. The authors describe a case of a 34-year-old pregnant woman with systemic mastocytosis who requests labor analgesia. An epidural analgesia was performed after induction of labor, after considering anesthetic particularities. The epidural procedure, labor and delivery were uneventful. A review of systemic mastocytosis is provided and its anesthetic considerations are discussed.


Assuntos
Analgesia Epidural , Anestesia , Anestesiologia , Mastocitose Sistêmica , Mastocitose , Adulto , Feminino , Humanos , Mastocitose Sistêmica/complicações , Gravidez
12.
Actas Urol Esp (Engl Ed) ; 46(5): 275-284, 2022 06.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35260370

RESUMO

OBJECTIVES: To evaluate the outcomes of robot-assisted radical prostatectomy (RARP) compared to those of open (ORP) and laparoscopic (LRP) surgery. The interest lies fundamentally in the quality-of-life (QoL) evaluation, postoperative recovery, and personal satisfaction of patients with the intervention (PS) beyond oncological and functional outcomes. METHODS: Six hundred eighty-five RPs were performed in our center between 2011-2018 (17,8% ORP, 22,2% LRP and 60% RARP). Patients were prospectively assessed through follow-up until April 2020 and a multiple questionnaire at 12-months post-RP that included ICIQ-SF, SHIM, IPSS, IQL and questions about pain, postoperative recovery and PS. Also baseline and postoperative patient- and treatment-related data were collected, and binomial logistic regressions were performed for the 1 vs.1 comparisons (ORP vs. RARP and LRP vs. RARP). RESULTS: RARP patients have overall fewer comorbidities, less tumor aggressiveness, more operative time requirements and more positive surgical margins than ORP and LRP patients. Nevertheless, RARP outperforms ORP in: hospital stay (days) (OR 0,86; 95% CI: 0,80-0,94), hemoglobin loss (OR 0,38; 95% CI: 0,30-0,47), transfusion rate (OR 0,18; 95% CI: 0,09-0,34), early complications (p = 0,001), IQL (OR 0,82; 95% CI: 0,69-0,98), erectile function (OR 0,41; 95% CI: 0,21-0,79), pain control (OR 0,82; 95% CI: 0,75-0,89), postoperative recovery (p < 0,001) and choice of a different approach (OR 5,55; 95% CI: 3,14-9,80). RARP is superior to LRP in: urinary continence (OR 0,55; 95% CI: 0,37-0,82), IPSS (OR 0,96; 95% CI: 0,93-0,98), IQL (OR 0,76; 95% CI: 0,66-0,88), erectile function (OR 0,52; 95% CI: 0,29-0,93), postoperative recovery (p = 0,02 and 0,004), PS (p = 0,005; 0,002; and 0,03) and choice of a different approach (OR 7,79; 95% CI: 4,63-13,13). CONCLUSIONS: The findings of our study globally endorse a positive effectiveness of RARP over ORP and/or LRP, both on functional issues, postoperative recovery, QoL and PS. Oncologic results should still be improved.


Assuntos
Disfunção Erétil , Procedimentos Cirúrgicos Robóticos , Disfunção Erétil/etiologia , Humanos , Masculino , Prostatectomia/métodos , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
13.
Braz. j. med. biol. res ; 55: e11820, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1374708

RESUMO

The aim of the present study was to verify the role of lactate as a signaling molecule in cardiac tissue under physiological conditions. C57BL6/J male mice were submitted to acute running bouts on a treadmill at different exercise intensities (30, 60, and 90% of maximal speed - Smax) under the effect of two doses (0.5 and 5 mM) of α-cyano-4-hydroxycynnamate (CINN), a blocker of lactate transporters. Cardiac lactate levels, activity of the enzymes of glycolytic [hexokinase (HK) and lactate dehydrogenase (LDH)] and oxidative metabolism [citrate synthase (CS)], and expression of genes also related to metabolism [LDH, nuclear factor erythroid 2-related factor 2 (NRF-2), cytochrome oxidase IV (COX-IV), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)] were evaluated. Elevated cardiac lactate levels were observed after high intensity running at 90% of Smax, which were parallel to increased activity of the HK and CS enzymes and mRNA levels of PGC-1α and COX-IV. No changes were observed in cardiac lactate levels in mice running at lower exercise intensities. Interestingly, prior intraperitoneal administration (15 min) of CINN (0.5 mM) significantly reduced cardiac lactate concentration, activities of HK and CS, and mRNA levels of PGC-1α and COX-IV in mice that ran at 90% of Smax. In addition, cardiac lactate levels were significantly correlated to both PGC-1α and COX-IV cardiac gene expression. The present study provides evidence that cardiac lactate levels are associated to gene transcription during an acute bout of high intensity running exercise.

14.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34154823

RESUMO

Mastocytosis is characterized by clonal expansion of mast cells, with abnormal accumulation in different organs. Perioperatively, numerous stimuli may lead to the release of vasoactive substances by mast cells. Parturients with systemic mastocytosis pose a challenge to the anesthesiologist: on one hand, the pain and stress of labor may lead to greater mast cell activation and, on the other, the administration of drugs that may possibly trigger the release of mast cell mediators. The authors describe a case of a 34-year-old pregnant woman with systemic mastocytosis who requests labor analgesia. An epidural analgesia was performed after induction of labor, after considering anesthetic particularities. The epidural procedure, labor and delivery were uneventful. A review of systemic mastocytosis is provided and its anesthetic considerations are discussed.

15.
Sci Rep ; 11(1): 3802, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589694

RESUMO

Pancreatic Ductal Adenocarcinoma (PDAC) has a five-year survival under 10%. Treatment is compromised due to a fibrotic-like stromal remodeling process, known as desmoplasia, which limits therapeutic perfusion, supports tumor progression, and establishes an immunosuppressive microenvironment. These processes are driven by cancer-associated fibroblasts (CAFs), functionally activated through transforming growth factor beta1 (TGFß1). CAFs produce a topographically aligned extracellular matrix (ECM) that correlates with reduced overall survival. Paradoxically, ablation of CAF populations results in a more aggressive disease, suggesting CAFs can also restrain PDAC progression. Thus, unraveling the mechanism(s) underlying CAF functions could lead to therapies that reinstate the tumor-suppressive features of the pancreatic stroma. CAF activation involves the f-actin organizing protein palladin. CAFs express two palladin isoforms (iso3 and iso4) which are up-regulated in response to TGFß1. However, the roles of iso3 and iso4 in CAF functions remain elusive. Using a CAF-derived ECM model, we uncovered that iso3/iso4 are required to sustain TGFß1-dependent CAF activation, secrete immunosuppressive cytokines, and produce a pro-tumoral ECM. Findings demonstrate a novel role for CAF palladin and suggest that iso3/iso4 regulate both redundant and specific tumor-supportive desmoplastic functions. This study highlights the therapeutic potential of targeting CAFs to restore fibroblastic anti-tumor activity in the pancreatic microenvironment.


Assuntos
Adenocarcinoma/genética , Carcinoma Ductal Pancreático/genética , Proteínas do Citoesqueleto/genética , Fator de Crescimento Transformador beta1/genética , Adenocarcinoma/patologia , Idoso , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Matriz Extracelular/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/metabolismo , Pâncreas/patologia , Isoformas de Proteínas/genética , Microambiente Tumoral/genética
16.
Arthrosc Tech ; 10(1): e103-e116, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33532216

RESUMO

Posterior shoulder dislocations are an uncommon cause of glenohumeral instability; they are frequently missed and are associated with humeral head defects and capsulolabral lesions. Despite surgical treatment often being mandatory, there is still no standardized treatment for anterior impaction fractures of the humeral head (reverse Hill-Sachs lesions). Arthroscopic surgery is typically indicated, with a tendency toward resorting to knotless techniques in recent years. We present a method for the treatment of posterior shoulder dislocations with engaging reverse Hill-Sachs lesions that achieves full defect coverage using an arthroscopic all-in-the-box knotless subscapularis bridge technique with 2 anchors-with one crossing the subscapularis tendon and the other embracing it-along with posterior capsulolabral complex restoration. This promising technique is a potentially superior alternative for the treatment of these lesions that can also be used in the presence of concomitant partial subscapularis tears.

17.
Leukemia ; 35(3): 835-849, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32595214

RESUMO

In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p < 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.


Assuntos
Biomarcadores Tumorais/análise , Síndromes Mielodisplásicas/classificação , Síndromes Mielodisplásicas/diagnóstico , Segunda Neoplasia Primária/classificação , Segunda Neoplasia Primária/diagnóstico , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Segunda Neoplasia Primária/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
18.
Braz. j. biol ; 80(3): 497-505, July-Sept. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1132403

RESUMO

Abstract Little is known regarding whether photodynamic therapy (PDT)-induced cell death can substantially compromise macrophages (MΦ), which are important cells in PDT-induced immune responses. Here, parameters of PDT-mediated MΦ cytotoxicity and cytokine production in response to protoporphyrin IX (PpIX) were evaluated. Peritoneal MΦ from BALB/c mice were stimulated in vitro with PDT, light, PpIX, or lipopolysaccharide (LPS). After that, cell viability, lipid peroxidation, Nitric Oxide (NO), DNA damage, TNF-α, IL-6 and IL-10 were evaluated. Short PDT exposure reduced cell viability by 10-30%. There was a two-fold increase in NO and DNA degradation, despite the non-increase in lipoperoxidation. PDT increased TNF-α and IL-10, particularly in the presence of LPS, and decreased the production of IL-6 to 10-fold. PDT causes cellular stress, induces NO radicals and leads to DNA degradation, generating a cytotoxic microenvironment. Furthermore, PDT modulates pro- and anti-inflammatory cytokines in MΦ.


Resumo Pouco se sabe se a morte celular induzida pela terapia fotodinâmica (PDT) compromete os macrófagos (MΦ), envolvidos nas respostas imunes induzidas pela PDT. Neste estudo, foram avaliados parâmetros de citotoxicidade dos MΦ mediada pela PDT e a produção de citocinas, frente à protoporfirina IX (PpIX). MΦ peritoneais de camundongos BALB/c foram estimulados in vitro com PDT, luz, PpIX ou lipopolissacarídeo (LPS). Após isto, a viabilidade celular (VC), a lipoperoxidação, os níveis de óxido nítrico (NO), de DNA degradado, de TNF-α, IL-6 e IL-10 foram avaliados. A exposição curta à PDT reduziu a VC em 10-30%. Os níveis de NO e de DNA degradado duplicaram, sem aumento da lipoperoxidação. Houve aumento de TNF-α e IL-10, sendo maior na presença de LPS. Já a produção de IL-6 reduziu em dez vezes. A PDT induz estresse celular, gera radicais NO e causa dano ao DNA, tornando o microambiente citotóxico. Ainda, modula citocinas pró e anti-inflamatórias em MΦ.


Assuntos
Animais , Coelhos , Fotoquimioterapia , Interleucina-10 , Protoporfirinas , Citocinas , Interleucina-6 , Fator de Necrose Tumoral alfa , Macrófagos , Camundongos Endogâmicos BALB C
19.
J Mater Chem B ; 8(36): 8422-8432, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32804177

RESUMO

Hydrogel-based regenerative endodontic procedures (REPs) are considered to be very promising therapeutic strategies to reconstruct the dental pulp (DP) tissue in devitalized human teeth. However, the success of the regeneration process is limited by residual bacteria that may persist in the endodontic space after the disinfection step and contaminate the biomaterial. The aim of this work was to develop an innovative fibrin hydrogel incorporating clindamycin (CLIN)-loaded Poly (d,l) Lactic Acid (PLA) nanoparticles (NPs) to provide the hydrogel with antibacterial properties. CLIN-PLA-NPs were synthesized by a surfactant-free nanoprecipitation method and their microphysical properties were assessed by dynamic light scattering, electrophoretic mobility and scanning electron microscopy. Their antimicrobial efficacy was evaluated on Enteroccocus fæcalis by the determination of the minimal inhibitory concentration (MIC) and the minimal biofilm inhibition and eradication concentrations (MBIC and MBEC). Antibacterial properties of the nanocomposite hydrogel were verified by agar diffusion assays. NP distribution into the hydrogel and release from it were evaluated using fluorescent PLA-NPs. NP cytotoxicity was assessed on DP mesenchymal stem cells (DP-MSCs) incorporated into the hydrogel. Type I collagen synthesis was investigated after 7 days of culture by immunohistochemistry. We found that CLIN-PLA-NPs displayed a drug loading of 10 ± 2 µg per mg of PLA polymer and an entrapment efficiency of 43 ± 7%. Antibiotic loading did not affect NP size, polydispersity index and zeta potential. The MIC for Enterococcus fæcalis was 32 µg mL-1. MBIC50 and MBEC50 were 4 and 16 µg mL-1, respectively. CLIN-PLA-NPs appeared homogenously distributed throughout the hydrogel. CLIN-PLA-NP-loaded hydrogels clearly inhibited E. faecalis growth. DP-MSC viability and type I collagen synthesis within the fibrin hydrogel were not affected by CLIN-PLA-NPs. In conclusion, CLIN-PLA-NP incorporation into the fibrin hydrogel gave the latter antibacterial and antibiofilm properties without affecting cell viability and function. This formulation could help establish an aseptic environment supporting DP reconstruction and, accordingly, might be a valuable tool for REPs.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/prevenção & controle , Polpa Dentária/fisiologia , Hidrogéis/química , Nanocompostos/química , Regeneração/efeitos dos fármacos , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Clindamicina/química , Clindamicina/uso terapêutico , Polpa Dentária/citologia , Liberação Controlada de Fármacos , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/fisiologia , Feminino , Fibrina/química , Fibrina/toxicidade , Humanos , Hidrogéis/toxicidade , Células-Tronco Mesenquimais/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Nanocompostos/toxicidade , Nanopartículas/química , Nanopartículas/toxicidade , Poliésteres/química , Poliésteres/toxicidade , Engenharia Tecidual/métodos
20.
Br J Oral Maxillofac Surg ; 58(7): 789-794, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32381388

RESUMO

An impacted third molar is one of the most common dental abnormalities. Among the reasons for impaction the most common are: insufficient space, time of eruption, improper position of the tooth bud, and genetic disruptions. To investigate if runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2), and msh homeobox 1 (MSX1) are differently expressed depending on the position of the molar, we studied 32 patients who had been referred for surgical removal. An orthopantomogram was used to separate them according to Winter's, and Pell & Gregory's, classifications. Bone samples were harvested during the operation for gene expression assay. The Kruskal-Wallis, Dunn's post hoc, and Spearman's correlation, tests were used to assess the significance of differences. No correlations were found in expression of the genes, and no differences between expression in maxillary and mandibular third molars, nor were they expressed differently according to Winter's or Pell and Gregory's classifications or in relation to impaction of the mandibular ramus. However, MSX1 was expressed differently when account was taken of the depth of impaction in maxillary third molars (p = 0.029), but there was no difference in expression of RUNX2, BMP2, and MSX1 for the Pell and Gregory classification of depth of impaction (p > 0.05). We conclude that MSX1 is expressed differently depending on the depth of maxillary impaction phenotypes.


Assuntos
Dente Serotino , Dente Impactado , Humanos , Fator de Transcrição MSX1 , Mandíbula , Dente Molar , Erupção Dentária
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