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BACKGROUND: In the context of rheumatoid arthritis and its systemic inflammatory implications, there is an increasing interest in investigating the role of prolactin in the clinical and metabolic aspects of the disease. This study aimed to explore the potential links between serum prolactin levels, serum glucose levels, and the clinical manifestations of arthritis. METHODS: This exploratory, cross-sectional, observational study focused on women diagnosed with rheumatoid arthritis. The research involved assessing prolactin and blood glucose concentrations, alongside specific clinical traits such as disease-related inflammation, morning stiffness, and fatigue intensity. The presence of changes in serum prolactin (PRL) was initially compared among the groups based on disease activity intensity. Using a multinomial regression analysis, the study analyzed the impact of predetermined clinical and metabolic factors on various categories of prolactin concentration. RESULTS: Out of the 72 participants included in the study, hyperprolactinemia was detected in 9.1% of the sample. No differences in serum PRL were identified among the evaluated groups based on disease activity. Following multivariate analysis, no statistically significant differences were identified for the outcomes of inflammatory activity and morning stiffness within each PRL category when compared to the reference category for PRL. There was no increased likelihood of encountering blood glucose levels below 100 mg/dl among individuals with higher prolactin concentrations compared to those in the lowest prolactin category (OR 5.43, 95% CI 0.51-58.28). The presence of clinically significant fatigue revealed a higher likelihood of encountering this outcome among patients with intermediate PRL values (prolactin categories 7.76-10.35 with OR 5.18, 95% CI 1.01-26.38 and 10.36-15.29 with OR 6.25, 95% CI 1.2-32.51) when compared to the reference category. CONCLUSIONS: The study found no discernible correlation between prolactin concentrations and worse scores for inflammatory activity of the disease, nor between prolactin concentrations and serum glucose levels. The findings regarding fatigue should be approached with caution given the exploratory nature of this study.
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Artrite Reumatoide , Glicemia , Hiperprolactinemia , Prolactina , Humanos , Prolactina/sangue , Artrite Reumatoide/sangue , Feminino , Estudos Transversais , Glicemia/análise , Pessoa de Meia-Idade , Hiperprolactinemia/sangue , Adulto , Índice de Gravidade de Doença , Fadiga/sangue , Fadiga/etiologiaRESUMO
This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of L. amazonensis (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC50 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC50 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of L. amazonensis, with IC50 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against L. amazonensis promastigotes and amastigotes, being a promising system for future in vivo trials.
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Emulsões , Macrófagos Peritoneais , Sesquiterpenos Monocíclicos , Sesquiterpenos , Pele , Animais , Sesquiterpenos Monocíclicos/farmacologia , Sesquiterpenos Monocíclicos/química , Emulsões/química , Camundongos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Pele/parasitologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Espectroscopia de Infravermelho com Transformada de Fourier , Absorção Cutânea/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Feminino , Leishmania/efeitos dos fármacos , Tensoativos/farmacologia , Tensoativos/química , Antiprotozoários/farmacologia , Antiprotozoários/químicaRESUMO
OBJECTIVE: To evaluate the association between psoriasis (PSO), psoriatic arthritis (PsA) and periodontitis (PE), and the Oral Health-Related Quality of Life (OHRQoL) impacts on individuals with psoriatic disease's daily activities compared to the non-psoriatic ones. MATERIALS & METHODS: 296 individuals with psoriatic disease (PSO n = 210, APS n = 86) (cases) and 359 without these diseases (controls) were included. Complete periodontal examinations and collection of variables of interest were performed. The Brazilian version of the Oral Impacts on Daily Performance (OIDP) instrument was applied. RESULTS: The prevalence of PE was higher in PsA (57.0%; OR = 2.67 95%CI 1.65-4.32; p<0.001) than in PSO (34.3%; OR = 1.05 95% CI 0.73-1.51; p<0.001) compared to controls (33.1%). Both PsA and PSO groups showed more sites and teeth with 4-6mm probing depth (PD) and had higher OIDP scores than controls (p<0.001), thus indicating worse self-reported quality of life. PE, PSO+PE and consumption of alcohol/anxiolytics significantly influenced OHRQoL (p<0.05). The influence of periodontal parameters on OHRQoL was observed for the presence of PE; PD >6 mm; clinical attachment level >6 mm; higher plaque index, % sites and teeth with bleeding on probing (p<0.05). CONCLUSION: Negative impacts of PE on the OHRQoL were demonstrated. The ones having PSO and especially PsA and PE presented significantly worse indicators.
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Artrite Psoriásica , Saúde Bucal , Periodontite , Psoríase , Qualidade de Vida , Humanos , Artrite Psoriásica/complicações , Artrite Psoriásica/psicologia , Artrite Psoriásica/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Psoríase/complicações , Psoríase/psicologia , Adulto , Periodontite/complicações , Periodontite/epidemiologia , Brasil/epidemiologia , Estudos de Casos e ControlesRESUMO
This study evaluated clinical features of individuals with long COVID (5-8 months after diagnosis) who reported sleep and memory problems (62 cases) compared to those without (52 controls). Both groups had a similar mean age (41 vs. 39 years). Around 86% of the participants were non-hospitalized at the time of infection, and none of them were vaccinated at that point. Subsequently, both cases and controls received the vaccine; however, the vaccination rates differed significantly between the groups (30.7% vs. 51.0%). Cases and controls had similar rates of symptoms at acute COVID phase. However, cases were more likely to experience coryza, dyspnea, headache, and nausea/vomiting during long COVID. Regarding new-onset symptoms in long COVID, 12.9% of cases had dyspnea, and 14.5% experienced nausea/vomiting, whereas in the control group there were only 1.9% and 0.0%, respectively. Cases also had a significantly higher prevalence of persistent headache (22.6% vs. 7.7%), and dyspnea (12.9% vs. 0.0). In addition, cases also showed an increased rate of mental health complaints: disability in daily activities (45.2% vs. 9.6%; P < 0.001); concentration/sustained attention difficulties (74.2% vs. 9.6%; P < 0.001); anxiety-Generalized Anxiety Disorder 2-item scale (GAD-2) ≥ 3 (66.1% vs. 34.6%; P = 0.0013); and "post-COVID sadness" (82.3% vs. 40.4%; P < 0.001). We observed a significant correlation between sadness and anxiety in cases, which was not observed in controls (P=0.0212; Spearman correlation test). Furthermore, the frequency of concomitant sadness and anxiety was markedly higher in cases compared to controls (59.7% vs. 19.2%) (P < 0.0001; Mann-Whitney test). These findings highlight a noteworthy association between sadness and anxiety specifically in cases. In conclusion, our data identified concurrent psychological phenotypes in individuals experiencing sleep and memory disturbances during long COVID. This strengthens the existing evidence that SARS-CoV-2 causes widespread brain pathology with interconnected phenotypic clusters. This finding highlights the need for comprehensive medical attention to address these complex issues, as well as major investments in testing strategies capable of preventing the development of long COVID sequelae, such as vaccination.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Síndrome de COVID-19 Pós-Aguda , Depressão/epidemiologia , Sono , Cefaleia/epidemiologia , Dispneia , Náusea , VômitoRESUMO
The aim of this study was to investigate the association between maternal and paternal licit and illicit drug use, smoking and drinking and autism spectrum disorder (ASD). We conducted a case-control study with children and adolescents diagnosed with ASD and neurotypical individuals. The data were collected using a semi-structured questionnaire administered during interviews with the children's mothers or guardians. The following variables were analyzed: child sex and age; maternal and parental age; use of medicines before and during pregnancy; classes of medicines used during pregnancy; maternal and paternal smoking; maternal and paternal drinking; maternal and paternal illicit drug use. The data were analyzed using logistic regression and crude and adjusted odds ratios (OR). After adjustment, the results showed an association between maternal use of antipyretics/pain killers during pregnancy (OR = 2.26; 95%CI 1.29-3.95; p < 0.040) and ASD. No association was found between maternal and paternal smoking, drinking and illicit drug use before and during pregnancy and ASD. The findings suggest that the development of ASD is influenced by environmental factors.
O presente estudo objetivou investigar a associação entre o TEA e o uso materno e paterno de medicamentos, tabaco, álcool e drogas ilícitas. Trata-se de um estudo caso-controle realizado com crianças e adolescentes diagnosticados com TEA e indivíduos neurotípicos. Os dados foram colhidos por meio de entrevista com as mães ou responsáveis. Foram analisadas as variáveis sexo e idade das crianças/adolescentes; idade dos pais; uso de medicamentos antes e durante a gestação; classes de medicamentos usados na gestação; tabagismo materno e paterno; etilismo materno e paterno; uso de drogas ilícitas pelos pais. Para a análise das informações, utilizou-se o modelo de regressão logística, além da razão de chances (OR) bruta e ajustada. Os resultados mostraram que, após os ajustes, foi encontrada associação entre o uso materno na gestação de antitérmicos/analgésicos (OR = 2,26; IC95% 1,29-3,95; p < 0,040) com o TEA. Já o uso de tabaco, álcool e drogas ilícitas materno e paterno, antes e durante a gestação, não apontou relação com o TEA. Os dados encontrados sugerem que existe influência de fatores ambientais no desenvolvimento do TEA.
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Transtorno do Espectro Autista , Drogas Ilícitas , Humanos , Gravidez , Criança , Feminino , Adolescente , Fatores de Risco , Estudos de Casos e Controles , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/etiologia , Fumar/epidemiologiaRESUMO
Resumo O presente estudo objetivou investigar a associação entre o TEA e o uso materno e paterno de medicamentos, tabaco, álcool e drogas ilícitas. Trata-se de um estudo caso-controle realizado com crianças e adolescentes diagnosticados com TEA e indivíduos neurotípicos. Os dados foram colhidos por meio de entrevista com as mães ou responsáveis. Foram analisadas as variáveis sexo e idade das crianças/adolescentes; idade dos pais; uso de medicamentos antes e durante a gestação; classes de medicamentos usados na gestação; tabagismo materno e paterno; etilismo materno e paterno; uso de drogas ilícitas pelos pais. Para a análise das informações, utilizou-se o modelo de regressão logística, além da razão de chances (OR) bruta e ajustada. Os resultados mostraram que, após os ajustes, foi encontrada associação entre o uso materno na gestação de antitérmicos/analgésicos (OR = 2,26; IC95% 1,29-3,95; p < 0,040) com o TEA. Já o uso de tabaco, álcool e drogas ilícitas materno e paterno, antes e durante a gestação, não apontou relação com o TEA. Os dados encontrados sugerem que existe influência de fatores ambientais no desenvolvimento do TEA.
Abstract The aim of this study was to investigate the association between maternal and paternal licit and illicit drug use, smoking and drinking and autism spectrum disorder (ASD). We conducted a case-control study with children and adolescents diagnosed with ASD and neurotypical individuals. The data were collected using a semi-structured questionnaire administered during interviews with the children's mothers or guardians. The following variables were analyzed: child sex and age; maternal and parental age; use of medicines before and during pregnancy; classes of medicines used during pregnancy; maternal and paternal smoking; maternal and paternal drinking; maternal and paternal illicit drug use. The data were analyzed using logistic regression and crude and adjusted odds ratios (OR). After adjustment, the results showed an association between maternal use of antipyretics/pain killers during pregnancy (OR = 2.26; 95%CI 1.29-3.95; p < 0.040) and ASD. No association was found between maternal and paternal smoking, drinking and illicit drug use before and during pregnancy and ASD. The findings suggest that the development of ASD is influenced by environmental factors.
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Glioblastoma (GBM) is an aggressive, common brain cancer known to disrupt redox biology, affecting behavior and DNA integrity. Past research remains inconclusive. To further understand this, an investigation was conducted on physical training's effects on behavior, redox balance, and genomic stability in GBMA models. Forty-seven male C57BL/6J mice, 60 days old, were divided into GBM and sham groups (n = 15, n = 10, respectively), which were further subdivided into trained (Str, Gtr; n = 10, n = 12) and untrained (Sut, Gut; n = 10, n = 15) subsets. The trained mice performed moderate aerobic exercises on a treadmill five to six times a week for a month while untrained mice remained in their enclosures. Behavior was evaluated using open-field and rotarod tests. Post training, the mice were euthanized and brain, liver, bone marrow, and blood samples were analyzed for redox and genomic instability markers. The results indicated increased latency values in the trained GBM (Gtr) group, suggesting a beneficial impact of exercise. Elevated reactive oxygen species in the parietal tissue of untrained GBM mice (Gut) were reduced post training. Moreover, Gtr mice exhibited lower tail intensity, indicating less genomic instability. Thus, exercise could serve as a promising supplemental GBM treatment, modulating redox parameters and reducing genomic instability.
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BACKGROUND: Patients with tuberculosis (TB) may develop multi-organ failure and require admission to intensive care. In these cases, the mortality rates are as high as 78% and may be caused by suboptimal serum concentrations of first-line TB drugs. This study aims to compare the pharmacokinetics of oral rifampin, isoniazid, pyrazinamide and ethambutol patients in intensive care units (ICU) to outpatients and to evaluate drug serum concentrations as a potential cause of mortality. METHODS: A prospective pharmacokinetic (PK) study was performed in Amazonas State, Brazil. The primary PK parameters of outpatients who achieved clinical and microbiological cure were used as a comparative target in a non-compartmental analysis. RESULTS: Thirteen ICU and twenty outpatients were recruited. The clearance and volume of distribution were lower for rifampin, isoniazid, pyrazinamide and ethambutol. ICU thirty-day mortality was 77% versus a cure rate of 89% in outpatients. CONCLUSIONS: ICU patients had a lower clearance and volume of distribution for rifampin, isoniazid, pyrazinamide and ethambutol compared to the outpatient group. These may reflect changes to organ function, impeded absorption and distribution to the site of infection in ICU patients and have the potential to impact clinical outcomes.
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Leishmaniases are neglected tropical diseases caused by obligate intracellular protozoa of the genus Leishmania. The drugs used in treatment have a high financial cost, a long treatment time, high toxicity, and variable efficacy. 3-Carene (3CR) is a hydrocarbon monoterpene that has shown in vitro activity against some Leishmania species; however, it has low water solubility and high volatility. This study aimed to develop Poloxamer 407 micelles capable of delivering 3CR (P407-3CR) to improve antileishmanial activity. The micelles formulated presented nanometric size, medium or low polydispersity, and Newtonian fluid rheological behavior. 3CR and P407-3CR inhibited the growth of L. (L.) amazonensis promastigote with IC50/48h of 488.1 ± 3.7 and 419.9 ±1.5 mM, respectively. Transmission electron microscopy analysis showed that 3CR induces multiple nuclei and kinetoplast phenotypes and the formation of numerous cytosolic invaginations. Additionally, the micelles were not cytotoxic to L929 cells or murine peritoneal macrophages, presenting activity on intracellular amastigotes. P407-3CR micelles (IC50/72 h = 0.7 ± 0.1 mM) increased the monoterpene activity by at least twice (3CR: IC50/72 h >1.5 mM). These results showed that P407 micelles are an effective nanosystem for delivering 3CR and potentiating antileishmanial activity. More studies are needed to evaluate this system as a potential therapeutic option for leishmaniases.
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BACKGROUND: Prospective studies have reported conflicting results regarding the adjunctive effect of antimicrobial photodynamic therapy (aPDT) on clinical and microbiological parameters in individuals under periodontal maintenance therapy (PMT). This study aimed to evaluate the clinical and microbiological adjunctive effects of aPDT using indocyanine green (ICG) in residual sites with probing depth (PD) ≥5 mm during PMT in comparison with scaling and root planing (SRP) alone. METHODS: A split-mouth randomized controlled clinical trial was conducted with 24 individuals in a PMT program. Contralateral quadrants with eligible residual sites were randomly assigned to either SRP + aPDT (test group) or SRP alone (control). aPDT included ICG dye and diode laser (909 nm) performed together with SRP and repeated 15 days after. Periodontal clinical parameters, periodontal inflamed surface area (PISA) index, and subgingival biofilm samples were collected at baseline (T1), 3 (T2), and 6 months later (T3). Microbiological analyses were performed by quantitative real-time polymerase chain reaction. RESULTS: Significant improvements were observed in all clinical and microbiological parameters in both groups from T1 to T3. However, no significant differences were observed regarding plaque index, PD, and clinical attachment level. Test group showed significantly greater reductions in bleeding on probing (BOP), PISA index, and Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans levels, when compared with controls. CONCLUSIONS: Both treatments resulted in significant clinical periodontal improvements, but with no significant differences between groups except from inflammation parameters. aPDT using ICG resulted in significant reductions in BOP and PISA index, as well as in P. gingivalis and A. actinomycetemcomitans levels.
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Periodontite Crônica , Fotoquimioterapia , Humanos , Verde de Indocianina/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Prospectivos , Periodontite Crônica/tratamento farmacológico , Periodontite Crônica/microbiologia , Fotoquimioterapia/métodos , Aplainamento Radicular/métodos , Raspagem Dentária/métodos , Terapia CombinadaRESUMO
BACKGROUND: The aim of this study was to evaluate the effect of supragingival plaque control on the recurrence of periodontitis (RP) and the achievement of a stable periodontal clinical endpoint after 10 years of periodontal maintenance therapy (PMT). METHODS: The present retrospective cohort study included 225 individuals in continuous PMT. The plaque index (PI) determining the oral hygiene (OH) status, periodontal clinical parameters, and other variables of interest were collected at three time points: T1 (prior to active periodontal therapy [APT]), T2 (after APT), and T3 (10 years after T2). According to PI records at T3, participants were categorized into: (1) good OH (GOH; PI ≤ 30%, n = 63); (2) fair OH (FOH; PI > 30% and ≤40%, n = 73); and (3) poor OH (POH; PI > 40%, n = 88). Data were analyzed using the chi-square and Student t tests, analysis of variance (ANOVA), and mediation and regression analyses. RESULTS: Significant differences in all periodontal clinical parameters between the GOH, FOH, and POH groups were observed at T3. The POH group exhibited higher mean bleeding on probing (BOP), periodontal probing depth (PD), and clinical attachment level (CAL), as well as higher tooth loss (POH > FOH > GOH; P < .001). There was an increased risk for RP in the FOH (odds ratio [OR] 2.02; CI, 1.10-4.38) and POH (OR 4.33; CI, 2.17-8.65) groups. Moreover, the FOH and POH groups had an approximately 2.5 and 6.0 times greater chance of not achieving a stable periodontal clinical endpoint, respectively. CONCLUSIONS: After 10 years of monitoring in PMT, individuals with higher PI scores (>30%) presented an unhealthier periodontal status, a higher risk for RP, and a lower chance of achieving ≤4 sites with PD ≥ 5 mm.
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Periodontite , Humanos , Seguimentos , Estudos Retrospectivos , Periodontite/terapia , Índice Periodontal , Perda da Inserção Periodontal , Índice de Placa DentáriaRESUMO
ABSTRACT New ways to obtain information on sedentary behavior (SB) have recently been explored. This study aimed at assessing the self-reported posture agreement by using the Ecological Momentary Assessment (EMA). The images were sent by an observation protocol created in a form that would be answered via the mobile phone of young adults. The bank of images was provided by 41 university students. Such images were obtained from a project carried out in 2019, which was based on the taxonomy of sedentary behavior. The following positions were assessed: sitting, lying/reclining and standing, comparing the images provided with the self-reported SB by using EMA, which was collected via cell phone. The agreement was assessed by two researchers independently. Data analysis was based on descriptive statistics, Student's t test, chi-squared test, and Cohen's k in SPSS 25 with P<0.05. The inter-rater reliability was strong/substantial, that is, 87.6% (rater 1; k = 0.696) and 88.6% (rater 2; k = 0.720). The image observation protocol created in an electronic form could discriminate the behavior adopted by the participants, as well as it could be used independently, only for recording EMA and/or the image/photograph.
RESUMO Novas formas de se obter informações sobre o comportamento sedentário (CS) têm sido exploradas recentemente. O objetivo do presente estudo foi verificar a concordância da postura auto-relatada por meio da Avaliação Momentânea Ecológica (AME). As imagens foram enviadas por meio de um protocolo de observação criado em um formulário respondido pelo telefone celular de adultos jovens. Foi utilizado um banco de imagens fornecido por 41 universitários, obtidas por um projeto realizado em 2019 com base na taxonomia do comportamento sedentário. As seguintes posições foram analisadas: sentada, deitado/reclinado ou em pé, comparando a imagem fornecida com o CS auto-reportado por meio da AME, que foi coletada por telefone celular. A concordância foi realizada por dois pesquisadores de modo independente. A análise dos dados foi realizada pela estatística descritiva, t de Student, qui-quadrado e k de Cohen no SPSS 25 com P<0,05. A concordância entre os avaliadores foi forte/substancial de 87,6% (avaliador 1; k = 0,696) e de 88,6% (avaliador 2; k = 0,720). O protocolo de observação por imagem criado por formulário eletrônico conseguiu discriminar o comportamento adotado pelos participantes, bem como viável de ser utilizado de modo independente, somente para o registro da AME e/ou da imagem/fotografia.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Estudantes , Comportamento Sedentário , Avaliação Momentânea Ecológica , Educação Física e Treinamento , Ensino Fundamental e Médio , FotografiaRESUMO
Prion Diseases or Transmissible Spongiform Encephalopathies are neurodegenerative conditions associated with a long incubation period and progressive clinical evolution, leading to death. Their pathogenesis is characterized by conformational changes of the cellular prion protein-PrPC-in its infectious isoform-PrPSc-which can form polymeric aggregates that precipitate in brain tissues. Currently, there are no effective treatments for these diseases. The 2,5-diamino-1,4-benzoquinone structure is associated with an anti-prion profile and, considering the biodynamic properties associated with 4-quinolones, in this work, 6-amino-4-quinolones derivatives and their respective benzoquinone dimeric hybrids were synthesized and had their bioactive profile evaluated through their ability to prevent prion conversion. Two hybrids, namely, 2,5-dichloro-3,6-bis((3-carboxy-1-pentyl-4-quinolone-6-yl)amino)-1,4-benzoquinone (8e) and 2,5-dichloro-3,6-bis((1-benzyl-3-carboxy-4-quinolone-6-yl)amino)-1,4-benzoquinone (8f), stood out for their prion conversion inhibition ability, affecting the fibrillation process in both the kinetics-with a shortening of the lag phase-and thermodynamics and their ability to inhibit the formation of protein aggregates without significant cytotoxicity at ten micromolar.
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Doenças Priônicas , Príons , Quinolonas , Humanos , Proteínas Priônicas , Príons/química , Doenças Priônicas/metabolismo , Polímeros , Translocação Genética , Benzoquinonas/farmacologiaRESUMO
In cancer, tumor cells and their neoplastic microenvironment can sculpt the immunogenic phenotype of a developing tumor. In this context, natural killer (NK) cells are subtypes of lymphocytes of the innate immune system recognized for their potential to eliminate neoplastic cells, not only through direct cytolytic activity but also by favoring the development of an adaptive antitumor immune response. Even though the protective effect against leukemia due to NK-cell alloreactivity mediated by the absence of the KIR-ligand has already been shown, and some data on the role of NK cells in myeloproliferative neoplasms (MPN) has been explored, their mechanisms of immune escape have not been fully investigated. It is still unclear whether NK cells can affect the biology of BCR-ABL1-negative MPN and which mechanisms are involved in the control of leukemic stem cell expansion. Aiming to investigate the potential contribution of NK cells to the pathogenesis of MPN, we characterized the frequency, receptor expression, maturation profile, and function of NK cells from a conditional Jak2V617F murine transgenic model, which faithfully resembles the main clinical and laboratory characteristics of human polycythemia vera, and MPN patients. Immunophenotypic analysis was performed to characterize NK frequency, their subtypes, and receptor expression in both mutated and wild-type samples. We observed a higher frequency of total NK cells in JAK2V617F mutated MPN and a maturation arrest that resulted in low-numbered mature CD11b+ NK cells and increased immature secretory CD27+ cells in both human and murine mutated samples. In agreement, inhibitory receptors were more expressed in MPN. NK cells from Jak2V617F mice presented a lower potential for proliferation and activation than wild-type NK cells. Colonies generated by murine hematopoietic stem cells (HSC) after mutated or wild-type NK co-culture exposure demonstrated that NK cells from Jak2V617F mice were deficient in regulating differentiation and clonogenic capacity. In conclusion, our findings suggest that NK cells have an immature profile with deficient cytotoxicity that may lead to impaired tumor surveillance in MPN. These data provide a new perspective on the behavior of NK cells in the context of myeloid malignancies and can contribute to the development of new therapeutic strategies, targeting onco-inflammatory pathways that can potentially control transformed HSCs.
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Células Matadoras Naturais , Transtornos Mieloproliferativos , Animais , Humanos , Camundongos , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Células Matadoras Naturais/metabolismo , Leucemia/genética , Leucemia/metabolismo , Ligantes , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologia , Microambiente Tumoral/genéticaRESUMO
Introdução:As pessoas passaram a consumir alimentos prontos e ultraprocessados cada vez mais e diminuíram o consumo de alimentos naturais. Consequentemente, têm aumentado o desenvolvimento de obesidade e outras doenças crônicas não transmissíveis. Esse processo de transição nutricional e epidemiológico tem sido influenciado pelo ambiente alimentar. Objetivo:avaliar o microambiente alimentar em mercados e restaurantes do município de Santa Cruz, Rio Grande do Norte. Metodologia:Trata-se deuma pesquisa transversal e descritiva, de abordagem quantitativa, realizada em 60 estabelecimentos comerciais fornecedores de alimentos naturais, industrializados e refeições prontas. Foram aplicados questionários, de acordo com a classificação do tipo deestabelecimento para verificação da disponibilidade, variedade, preço e qualidade de alimentos naturais e ultraprocessados. Resultados:A maior parte dos estabelecimentos participantes eram mercados locais ou de bairros, localizados no centro da cidade, evidenciando as desigualdades territoriais.Foi visto que a disponibilidade de frutas e hortaliças era inferior aos ultraprocessados. Os alimentos apresentaram qualidade satisfatória e os menores preços de frutas foram encontrados nos supermercados e mercadinhos, enquanto os das hortaliças na feira livre. Conclusões:ficou evidente a necessidade de políticas públicas de incentivo a descentralização do comércio de alimentos e o incentivo à venda de alimentos mais saudáveis e acessíveis física e financeiramente (AU).
Introduction:People have started to consume more and more ready-to-eat foods and have reduced their consumption of fruit and vegetables. Consequently, the prevalence of overweight and chronic non-communicable diseases have increased over the years. This dietary and epidemiological transition process has been influenced by the food environment in which they are inserted. Objective:to evaluate the food microenvironment in markets and restaurants in the city of Santa Cruz, Rio Grande do Norte.Methodology:This is a cross-sectional and descriptive research, with a quantitative approach, carried out in 60 commercial establishments supplying natural and processed foods and ready-to-eat meals. Questionnaires were applied, according to the classification of the type of establishment, to check the availability, variety, price and quality of natural and ultra-processed foods.Results:Most of the participating establishments were local or neighborhood markets,located in the downtown, highlighting territorial inequalities. It was noted that the availability of fruits and vegetables is lower than the ultra-processed foods. All foods showed satisfactory quality, and the lowest prices for fruits were found in supermarkets and grocery stores, while vegetables were found in the street market. Conclusions:the need for public policies to encourage the decentralization of the food trade and the incentive to sell healthier and more affordable foodsphysically and financially became evident (AU).
Introducción: Las personas pasaron a consumir alimentos listos y ultraprocessados cada vez más y disminuyeron el consumo de alimentos naturales. Consecuentemente, las prevalencias de sobrepeso y enfermedades crónicas no transmisibles han aumentado con los años. Este proceso de transición alimentaria y epidemiológica ha sido influenciado por el entorno alimentario en el que se encuentran. Objetivo: evaluar el microambiente alimentario en mercados y restaurantes del municipio de Santa Cruz, Rio Grande do Norte.Metodología: Se trata de una investigación transversal y descriptiva, de abordaje cuantitativo, realizada en 60 establecimientos comerciales proveedores de alimentos naturales, industrializados y comidas preparadas. Se aplicaron cuestionarios de acuerdo con la clasificación del tipo de establecimiento para verificar la disponibilidad, variedad, precio y calidad de los alimentos naturales y ultraprocesados. Resultados: La mayor parte de los establecimientos participantes eran mercados locales o de barrios, localizada en el centro de la ciudad, destacando las desigualdades territoriales. Se ha visto que la disponibilidad de frutas y hortalizas es inferior a los ultraprocesados. Los alimentos presentaron calidad satisfactoria y los menores precios de frutas fueron encontrados en los supermercados y mercadillos, mientras que las hortalizas en la feria libre.Conclusiones: quedó evidente la necesidad de políticas públicas de incentivo a la descentralización del comercio de alimentos y el incentivo a la venta de alimentos más saludablesy asequibles física y financieramente (AU).
Assuntos
Política Pública , Ingestão de Alimentos , Alimentos Industrializados , Comportamento Alimentar/psicologia , Serviços de Alimentação , Restaurantes/estatística & dados numéricos , Verduras , Brasil/epidemiologia , Estudos Transversais/métodos , Inquéritos e Questionários , FrutasRESUMO
Glioma 261 (Gl261) cell-mediated neurotoxicity has been reported in previous studies examining glioblastoma (GBM), and the effects of physical exercise (PE) on this neurotoxicity have been poorly investigated. This study aimed to evaluate the effects of a PE program in animals with experimental GBM. Male C57BL/6J mice were randomized into sham or GBM groups and subjected to a PE program for four weeks. Gl261 cells were administered into the intraventricular region at 48 h after the last exercise session. Body weight, water and feed consumption, and behavior were all evaluated for 21 days followed by euthanasia. The right parietal lobe was removed for the analysis of glial fibrillary acidic protein (GFAP), epidermal growth factor receptor (EGFR), vimentin, C-myc, nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), hydrogen peroxide, the glutathione system, and oxidative damage to proteins. The results revealed changes in the behavioral patterns of the trained animals, and no anatomopathological changes were observed in response to PE training. In contrast, animals with GBM subjected to PE exhibited lower immunoexpression of c-MYC, vimentin, and GFAP. Although experimental GBM altered the redox profile and inflammatory mediators, no significant alterations were observed after PE. In conclusion, our data provide consistent evidence of the relationship between PE and the improvement of tumorigenic parameters against the neurotoxicity of GL261 cells.
Assuntos
Glioblastoma , Glioma , Animais , Encéfalo/metabolismo , Receptores ErbB/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Glioblastoma/patologia , Glioma/patologia , Glutationa , Peróxido de Hidrogênio , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Teóricos , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Vimentina/metabolismo , ÁguaRESUMO
Objetivou-se revisar e descrever, com base na literatura nacional e internacional, estudos que abordem a importância do conhecimento de docentes escolares sobre atendimento pré-hospitalar e respectiva aplicação, na prática, mediante revisão integrativa. Para tal, selecionaram-se artigos publicados entre 2016 e 2020, nas bases bibliográficas Scientific Electronic Library Online (SciELO), Medical Literature Analysis and Retrieval System Online (MEDLINE) e Literatura do Caribe em Ciências da Saúde (MEDCARIB). Em conclusão, ainda que parte considerável dos professores de ensino fundamental tenha tido que lidar com alguma situação de emergência, a quantidade deles com conhecimento técnico e atitudes adequadas ao manejo de situações emergenciais no ambiente escolar ainda é escassa. Deste modo, registra-se a importância da parceria entre os profissionais de saúde e educação, com intuito de desenvolver estratégias que viabilizem a prevenção de agravos de saúde em situações emergenciais no ambiente escolar.
RESUMO
BACKGROUND: Microbial resistance has become a worldwide public health problem and may lead to morbidity and mortality in affected patients. OBJECTIVES: Therefore, this work aimed to evaluate the antibacterial activity of quinone-4- oxoquinoline derivatives. METHODS: These derivatives were evaluated against Gram-positive and Gram-negative bacteria by their antibacterial activity, anti-biofilm, and hemolytic activities and in silico assays. RESULTS: The quinone-4-oxoquinoline derivatives presented broad-spectrum antibacterial activities and, in some cases, were more active than commercially available reference drugs. These compounds also inhibited bacterial adhesion, and the assays revealed seven non-hemolytic derivatives. The derivatives seem to cause damage to the bacterial cell membrane, and those containing the carboxyl group at the C-3 position of the 4-quinolonic nucleus were more active than those containing a carboxyethyl group. CONCLUSION: The isoquinoline-5,8-dione nucleus also favored antimicrobial activity. The study showed that the target of the derivatives must be a non-conventional hydrophobic allosteric binding pocket on the DNA gyrase enzyme.
Assuntos
Bactérias Gram-Negativas , Quinolonas , 4-Quinolonas , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias Gram-Positivas , Humanos , Testes de Sensibilidade Microbiana , Quinolonas/farmacologia , Quinonas/farmacologia , Relação Estrutura-AtividadeRESUMO
Orthopaedic surgeries can lead to pain that is difficult to treat, sometimes requiring prolonged hospitalisation. Peripheral nerve blocks stand out as an efficient strategy within the context of multimodal analgesia. The hypothesis is that continuous pericapsular nerve group block, when combined with lateral femoral cutaneous nerve block, can provide excellent analgesic coverage for hip surgeries. Continuous infusion systems can prolong analgesia, minimising opioid consumption, adverse effects and providing faster recovery. We describe a case of efficient analgesia, in which a catheter was positioned between the iliopsoas muscle plane and the iliopubic eminence for total hip arthroplasty.
Assuntos
Analgesia , Artroplastia de Quadril , Bloqueio Nervoso , Artroplastia de Quadril/efeitos adversos , Nervo Femoral , Humanos , Coxa da PernaRESUMO
O objetivo deste estudo foi a adaptação e validação da entrevista Friends and Family Interview que avalia o estilo de apego e a função reflexiva de crianças e adolescentes. Para adaptação, foram avaliadas a equivalência semântica, idiomática, experiencial e conceitual entre a versão traduzida e o instrumento original. A versão final da entrevista foi aplicada a uma amostra clínica de jovens entre 9 e 17 anos (M=13,12; DP=2,72) do sul do Brasil. Constatou-se que a versão em português apresentou uma consistência interna alta (α=0,79), assim como uma boa concordância entre avaliadores (α=0,89). A análise fatorial exploratória revelou dois componentes principais que melhor explicaram os dados, denominados Segurança nos Relacionamentos e Funcionamento Reflexivo (α=0,95) e Insegurança do Apego (α=0,72). Os resultados apoiaram a validade de construto e de critério da FFI e forneceram evidências de sua utilidade na avaliação do apego e da função reflexiva na infância e adolescência. (AU)
The study aimed to adapt and validate the Friends and Family Interview that assesses the attachment style and the reflective function in children and adolescents. The semantic, idiomatic, experiential and conceptual equivalences between the original and the translated version were analyzed. Then the final version was applied in a clinic sample of young people ranging from 9 to 17 years of age (M=13.12 SD=2.72 years), of southern Brazil. The statistical tests showed a high internal consistency (α=.79), as well as a good inter-evaluators reliability (α=.89) in the Portuguese version of the FFI. Exploratory factor analysis yielded two main factors, Relationships Security and Reflective Functioning (α=.95) and Attachment Insecurity (α=.72). The data supported the construct and criterion validities of the Portuguese version of the interview protocol. The FFI is a useful tool for the evaluation of attachment and reflective function in children and adolescents. (AU)
El objetivo de este estudio fue la adaptación y la validación de la entrevista Friends and Family Interview (FFI) que evalúa el estilo de apego y la función reflexiva de niños y adolescentes. Para la adaptación se evaluó la equivalencia semántica, idiomática, experiencial y conceptual entre la versión traducida y el instrumento original. La versión final de la entrevista se aplicó a una muestra clínica de jóvenes entre 9 y 17 años (M=13,12; DS=2,72) del sur de Brasil. Se encontró que la versión portuguesa tenía una alta consistencia interna (α=0,79), así como una buena concordancia entre evaluadores (α=0,89). El análisis factorial exploratorio reveló dos componentes principales, denominados Seguridad en las Relaciones y Funcionamiento Reflexivo (α=0,95) e Inseguridad del Apego (α=0,72). Los resultados apoyaron la validez de criterio y constructo de la FFI y proporcionaron evidencias de su utilidad para evaluar el apego y la función reflexiva en la niñez y en la adolescencia. (AU)