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Acanthamoeba spp. emerged as a clinically important pathogen related to amoebic keratitis. It is among the main causes of corneal transplantation and vision loss in ophthalmology. The treatment protocols have a low cure rate, high toxicity, and need for drug combination. Transition metal compounds have shown promising antiprotozoal effects. This study evaluates the amoebicidal activity of copper(II) coordination compounds in combination with chlorhexidine and the cytotoxicity to topical ocular application. These copper(II) coordination compounds were screened against Acanthamoeba castellanii trophozoites (ATCC 50492). The cytotoxicity on rabbit corneal cell line (ATCC-CCL 60) was performed. The compounds showed high amoebicidal potential, with inhibition of trophozoite viability above 80%. The Cp12 and Cp13 compounds showed Minimal Inhibitory Amoebicidal Concentration (MIAC) at 200 µM and mean inhibitory concentration (IC50) values lower than 10 µM. Against the cysts, Cp12 showed a reduction in viability (48%) in the longest incubation period. A synergistic effect for Cp12 with chlorhexidine was observed. The compounds have a dose-dependent effect against rabbit corneal cells. Compound Cp12 has potential for future application in developing ophthalmic formulations against Acanthamoeba keratitis and its use in multipurpose solutions is highlighted.
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Considering the key role of the corpus luteum in the regulation of the canine diestrus, the present study aimed to investigate changes in the luteal transcriptome of pseudopregnant dogs (n = 18) from days (D) 10, 20, 30, 40, 50 and 60 post-ovulation. After RNAsequencing was performed, data was analyzed by resorting to several informatic tools. A total of 3300 genes were differently expressed among all samples (FDR < 0.01). By comparing different time points, enriched biological processes as response to estradiol and lipids (D20 vs D10) and intracellular cholesterol transport (D40 vs D60) were observed. Moreover, LXR/RXR (liver X receptor- retinoid X receptor) signaling appeared as an overrepresented pathway in all comparisons. Thus, the expression of 19 genes involved in intracellular cholesterol availability was further evaluated; most were affected by time (P < 0.05). Adding to the deep transcriptomic analysis, presented data implies the importance of cholesterol regulation in luteal physiology of pseudopregnant dogs.
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Corpo Lúteo , Perfilação da Expressão Gênica , Animais , Colesterol , Cães , Estradiol , Feminino , Progesterona , TranscriptomaRESUMO
BACKGROUND: Non-metastatic castration resistant prostate cancer (M0 CRPC) has seen important developments in drugs and diagnostic tools in the last two years. New hormonal agents have demonstrated improvement in metastasis free survival in M0 CRPC patients and have been approved by regulatory agencies in Brazil. Additionally, newer and more sensitive imaging tools are able to detect metastasis earlier than before, which will impact the percentage of patients staged as M0 CRPC. Based on the available international guidelines, a group of Brazilian urology and medical oncology experts developed and completed a survey on the diagnosis and treatment of M0 CRPC in Brazil. These results are reviewed and summarized and associated recommendations are provided. OBJECTIVE: To present survey results on management of M0 CRPC in Brazil. DESIGN, SETTING, AND PARTICIPANTS: A panel of six Brazilian prostate cancer experts determined 64 questions concerning the main areas of interest: 1) staging tools, 2) treatments, 3) side effects of systemic treatment/s, and 4) osteoclast-targeted therapy. A larger panel of 28 Brazilian prostate cancer experts answered these questions in order to create country-specific recommendations discussed in this manuscript. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on the predefined questions. These answers are the panelists' opinions, not a literature review or meta-analysis. Therapies not yet approved in Brazil were excluded from answer options. Each question had five to seven relevant answers including two non-answers. Results were tabulated in real time. CONCLUSIONS: The results and recommendations presented can be used by Brazilian physicians to support the management of M0 CRPC patients. Individual clinical decision making should be supported by available data, however, for Brazil, guidelines for diagnosis and management of M0 CRPC patients have not been developed. This document will serve as a point of reference when confronting this disease stage.
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Consenso , Médicos , Neoplasias de Próstata Resistentes à Castração , Brasil , Humanos , Masculino , Seleção de Pacientes , Percepção , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Resultado do TratamentoRESUMO
This letter to the Editor aims to provide suggestions and recommendations for the management of urological conditions in times of COVID-19 crisis in Brazil and other low- and middle-income countries. It is important to highlight that one of the main characteristics of this pandemic is the oversaturation of the health system capacity, mostly due to a high demand for personal protective equipment (PPE), Hospital/ICU beds, as well as ventilators. In places with limited resources and where the health care systems are already saturated, such consideration is even more worrisome. Therefore, most worldwide authorities are recommending to avoid, as much as possible, patient's elective visits to hospitals, as well as a judicious use of the operating room in order to mitigate the strain put on the health system. While efforts should be directed to the care of COVID-19 patients, other conditions (especially urgencies and oncological cases) must continue to be assisted. Thus, through a panel of experts, we have prepared a practical guide for Thus, through a panel of experts, we have prepared a practical guide for urologists based on the recommendations from the main Urologic Associations, as well as data from the literature to support the suggested management. We will try to follow the standard guideline recommendations from the American Urological Association (AUA) and European Association of Urology (EAU), with the aim of pursuing the best outcomes possible. However, some recommendations were based on the consensus of the panel, taking into consideration the reality of developing countries and the unprecedented situation caused by the COVID-19 crisis. Most importantly, all recommendations on this manuscript are based on the expectancy of a maximum 3-month duration of the crisis. If this period shall extended, these recommendations will be revised and updated.
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Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Padrões de Prática Médica/normas , Urologistas/normas , Brasil/epidemiologia , COVID-19 , Humanos , Pandemias , Equipamento de Proteção Individual/normas , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
This study aimed to determine the histological features of the endometrium of bitches, as well as the cell proliferation at specific moments of diestrus, 10, 20, 30, 40, 50 and 60 days post ovulation, correlating the endometrial thickness with the uterine cell proliferation and the metabolic state (weight, blood glucose and plasma cholesterol) of the animals. Therefore, the right and left uterine horns of 26 clinically healthy bitches submitted to ovariohysterectomy were histologically analyzed 10, 20, 30, 40, 50 and 60 days post ovulation. The hematoxylin-eosin and AgNOR staining techniques were performed. All parameters were evaluated by ANOVA and post-hoc Tukey test (p<0.05). The correlation between endometrial thickness and uterine cell proliferation, weight, blood glucose and plasma cholesterol of animals was observed using the Pearson method (p<0.05). In the present study, it is concluded that endometrial thickness does not differ at any of the moments analyzed in diestrus. The endometrial thickness is not influenced by hormones, weight, blood glucose or serum cholesterol of bitches in this phase of the estrous cycle. However, there is greater cell proliferation in the endometrium at day 40 compared to day 60 post ovulation under the influence of the endocrine profile.
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Proliferação de Células/fisiologia , Colesterol/sangue , Diestro/fisiologia , Endométrio/citologia , Glucose/análise , Animais , Diestro/metabolismo , Cães , Endométrio/fisiologia , Feminino , Fatores de TempoRESUMO
Diuron, a high volume substituted urea herbicide, induced high incidences of urinary bladder carcinomas and low incidences of kidney pelvis papillomas and carcinomas in rats exposed to high doses (2500 ppm) in a 2-year bioassay. Diuron is registered for both occupational and residential uses and is used worldwide for more than 30 different crops. The proposed rat urothelial mode of action (MOA) for this herbicide consists of metabolic activation to metabolites that are excreted and concentrated in the urine, leading to cytotoxicity, urothelial cell necrosis and exfoliation, regenerative hyperplasia, and eventually tumors. We show evidence for this MOA for diuron using the International Programme on Chemical Safety (IPCS) conceptual framework for evaluating an MOA for chemical carcinogens, and the United States Environmental Protection Agency (USEPA) and IPCS framework for assessing human relevance.
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Diurona/toxicidade , Herbicidas/toxicidade , Neoplasias da Bexiga Urinária/patologia , Animais , Segurança Química , Modelos Animais de Doenças , Diurona/farmacocinética , Relação Dose-Resposta a Droga , Herbicidas/farmacocinética , Humanos , Ratos , Toxicocinética , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/induzido quimicamente , Urotélio/efeitos dos fármacos , Urotélio/patologiaRESUMO
White crowberries (Corema album) are a fruit from an endemic shrub found in Southern European Atlantic costal dunes. Although this shrub and its fruits never became a formal commercial crop for a number of reasons, it has a long-lasting relevance and tradition, much associated with summer, beach and holidays. The main goal of this study was to conduct a thematic analysis of the words and small expressions people associate with white crowberries. For that, a questionnaire was used, and the participants were asked to indicate in an open-ended question which top-of-mind words/small expressions they associate with white crowberries. A total of 501 people participated in this study, of which only 394 knew about white crowberries, and from those, only 229 answered the open-ended question of interest to this purpose. The results showed that the words/small expressions given by the participants were distributed between five categories (1-Memories of places, people and times, 2-Emotions and experiences, 3-Sensorial perception, 4-Properties and uses, and 5-Natural resources' valuation). Additionally, 18 subcategories were also identified. The most representative of the categories was sensorial perception and the most relevant of the subcategories was habitats (a subcategory from category 1). The most frequent words mentioned by the participants were beach, berry and summer. In addition, the effect of sociodemographic groups was investigated and some variations were observed in the categories of the words mentioned by the participants according to sex, living environment or region. This work allowed for the identification of a high variability in the words or expressions that account for a rich patrimony of tacit knowledge, memories, emotions and perceptions of the population towards white crowberries, thus confirming their social as well as nutritional relevance.
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BACKGROUND: Sepsis is a complex condition characterized by systemic host inflammation caused by an infection. Experimental and observational studies indicate that obesity, one of the components of metabolic syndrome (MetS), or aspirin (ASA) treatment could be associated with sepsis survival. However, the effects of ASA on septic mice with MetS-induced conditions have not been explored. METHODS: Swiss mice were administered monosodium glutamate (MSG) (4 mg/kg) during their first 5 days of life for MetS induction, while the control mice received an equimolar saline solution. MetS was validated in male mice on their 60th day of life. ASA treatment was administered for 15 days prior to sepsis (40 mg/kg). On the 75th day, sepsis was induced in MetS and control mice through cecal ligation and puncture (CLP). The effects of ASA on septic mice with MSG-induced MetS were assessed by determining survival rates, quantification of nitric oxide (NO), and cytokine levels in the plasma, while correlating these data with hematological, blood glucose and cardiovascular parameters. RESULTS: MetS was validated by Lee-Index (3 body weight/naso-anal length×1000), hypertension, and hyperglycemia in animals receiving MSG as neonates. In control animals, severe sepsis promoted hypoglycemia, which was associated with mortality, as well as increased plasma NO levels, hypotension, hematological alterations, and elevation of proinflammatory cytokines. In contrast, MetS and pre-treatment with ASA were able to prevent sepsis-related alterations. CONCLUSIONS: MetS and ASA pre-treatment provided protection against severe sepsis. However, ASA was ineffective in mice with MetS undergoing severe sepsis.
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Aspirina , Citocinas , Síndrome Metabólica , Óxido Nítrico , Sepse , Animais , Sepse/tratamento farmacológico , Aspirina/uso terapêutico , Aspirina/administração & dosagem , Camundongos , Masculino , Síndrome Metabólica/tratamento farmacológico , Citocinas/sangue , Óxido Nítrico/metabolismo , Modelos Animais de Doenças , Glutamato de Sódio , Glicemia/análiseRESUMO
Introduction: Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease. Methods: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study in patients with multi-vessel chronic coronary artery disease. Patients were randomized to receive IV infusions of LDE-paclitaxel (paclitaxel dose: 175â mg/m2 body surface) or LDE alone (placebo group), administered every 3 weeks for 18 weeks. All participants received guideline-directed medical therapy. Clinical and laboratory safety evaluations were made at baseline and every 3 weeks until the end of the study. Analysis of inflammatory biomarkers and coronary CTA was also performed at baseline and 4 weeks after treatment. Results: Forty patients aged 65.6 ± 8 years, 20 in LDE-paclitaxel and 20 in placebo group were enrolled. Among those, 58% had diabetes, 50% had myocardial infarction, and 91% were in use of statin and aspirin. Baseline demographics, risk factors, and laboratory results were not different between groups. In all patients, no clinical or laboratory toxicities were observed. From the baseline to the end of follow-up, there was a non-significant trend toward a decrease in IL-6 levels and hsCRP in the LDE-paclitaxel group (-16% and -28%, respectively), not observed in placebo. Regarding plaque progression analysis, variation in plaque parameter values was wide, and no difference between groups was observed. Conclusion: In patients with multivessel chronic coronary artery disease and optimized medical therapy, LDE-paclitaxel was safe and showed clues of potential benefits in reducing inflammatory biomarkers. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT04148833, identifier (NCT04148833).
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PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , América Latina , Consenso , SunitinibeRESUMO
Folie a trois is a syndrome characterized by the transfer of delusional ideas from one person to two other persons. This condition rarely ends in the murder of any involved and we are unaware of where the primary case had the diagnosis of acute psychosis in systemic lupus erythematosus (SLE). We present a case report of folie a trois resulting in murder, secondary to acute psychosis in SLE.
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Homicídio/psicologia , Lúpus Eritematoso Sistêmico/complicações , Transtorno Paranoide Compartilhado/complicações , Adulto , Feminino , Humanos , Lúpus Eritematoso Sistêmico/psicologia , Masculino , Pessoa de Meia-Idade , Transtorno Paranoide Compartilhado/psicologiaRESUMO
When students enter university, they suffer adaptations, including, usually, greater autonomy and responsibility for the choices they make. Therefore, it is crucial that they are well informed so as to make healthier food choices. The aim of this study was to determine whether sociodemographic characteristics, academic performance and lifestyle (tobacco and alcohol consumption) interfere with food literacy in university students. A quantitative, analytical, descriptive, transversal and correlational study was carried out, using quantitative data obtained through a questionnaire survey applied to a sample of 924 university students in Portugal. Food literacy was assessed through a scale of 27 items, distributed in three dimensions: D1-Literacy about food nutritional value and composition, D2-Literacy about labelling and food choice and D3-Literacy about healthy eating practices. Results showed no differences in food literacy according to sex or age. However, food literacy varied significantly with nationality, either globally (p = 0.006) or in the different dimensions evaluated (p-values of 0.005, 0.027 and 0.012 for D1, D2 and D3, respectively). In terms of academic achievement, the results showed no significant differences according to self-reported academic performance or even to the average classification obtained in the course. Regarding lifestyle variables, it was observed that alcohol consumption or smoking are not associated with food literacy, that is, food literacy does not vary significantly with these two lifestyle variables. In conclusion, food literacy in general and the dimensions evaluated are essentially constant among university students in Portugal, only varying for students from abroad. These results help to better perceive the food literacy levels for the population under study, university students, and that can be a valuable tool to better increase food literacy at these institutions as a way to better prepare for a healthier life and proper food habits that can enhance health in the long term.
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INTRODUCTION: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. METHODS: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. RESULTS: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer. DISCUSSION: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.
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Neoplasias de Próstata Resistentes à Castração , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/terapia , Humanos , Masculino , Estadiamento de Neoplasias , Antineoplásicos/uso terapêutico , Antagonistas de Receptores de Andrógenos/uso terapêutico , Consenso , Brasil , OsteoclastosRESUMO
The situation caused by the COVID-19 pandemic brought negative consequences such as social isolation, limited access to routine health and social care services, and lack of self-esteem, especially for older people. In this context, technology took on an important role as the main means of communication and service delivery. The main objective of this study is to analyze the situation of the elderly and their access to technological resources in the time of COVID-19. Based on a qualitative methodology, 58 semi-structured interviews were conducted with people between 65 and 90 years old in Portugal. The results reveal specific difficulties in the use of this type of digital devices and a change in the digital use profile of this age group, characterized by more frequent use of digital devices such as smartphones, the incorporation of certain services such as video calls, and uses associated with communication and entertainment. This study shows that attitudes toward technology among the elderly should be studied further, and these results should be considered to develop and implement training programs specially designed for this age group in order to contribute to their well-being and quality of life.
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COVID-19 , Pandemias , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Humanos , Qualidade de Vida , Isolamento Social , TecnologiaRESUMO
Eating behaviors and healthy food choices are associated with food literacy, and they have a huge impact on one's health status. For that reason, to increase food literacy is a way to effectively help individuals make appropriate choices that help maintain health and diminish the incidence of non-communicable diseases. The objective of this work was to test and validate a scale to assess food literacy. The validation was conducted on a sample of 924 Portuguese university students. The scale was composed of 50 items, which were submitted to exploratory and confirmatory factors analysis. The final validated scale corresponded to a second-order model with a global factor called "Food literacy", which retained 26 items distributed by three factors: F1-literacy about the nutritional composition of foods (10 items), F2-literacy about labelling and food choices (7 items), and F3-literacy about healthy eating practices (9 items). The internal consistency of the scale is very high, with an alpha higher than 0.9, and the Pierson correlations between the three factors and the global are also higher than 0.9. In conclusion, the present scale has been validated and can therefore be utilized to measure food literacy.
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Comportamento Alimentar , Letramento em Saúde , Humanos , Portugal , Universidades , Análise Fatorial , Estudantes , Inquéritos e Questionários , Reprodutibilidade dos Testes , PsicometriaRESUMO
Glucose uptake increases in canine luteal cells under insulin treatment. We hypothesize that insulin also increases luteal cell steroidogenesis. Dogs underwent elective ovariohysterectomy from days 10-60 post ovulation and their corpora lutea (CL) and blood samples were collected. Deep RNA sequencing determined differentially expressed genes in CL; those related to insulin signaling and steroidogenesis were validated in vivo by qPCR and their respective proteins by Western blotting and immunofluorescence. Next, luteal cell cultures were stimulated with insulin with or without inhibition of MAPK14, MAP2K1 and PI3K. Studied proteins except P450 aromatase showed the same expression pattern of coding genes in vivo. The expression of HSD3B and CYP19A1 was higher in insulin-treated cells (P < 0.005). Following respective pathway blockades, the culture medium had decreased concentrations of progesterone (P4) and 17b-estradiol (E2) (P < 0.01). Our results indicate that insulin increases HSD3B and CYP19A1 expression via MAPK and PI3K, and contributes to the regulation of P4 and E2 production in canine luteal cells.
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Insulina/farmacologia , Células Lúteas/efeitos dos fármacos , Esteroides/biossíntese , Animais , Células Cultivadas , Corpo Lúteo/efeitos dos fármacos , Corpo Lúteo/metabolismo , Cães , Estradiol/metabolismo , Feminino , Glucose/metabolismo , Células Lúteas/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Progesterona/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Two platinum complexes [Pt(HL3)Cl]·H2O (3) and [Pt(HL4)Cl]·H2O (4) containing α- and ß-naphthyl groups, respectively, were investigated in more detail in vitro and in vivo for antineoplastic activity. The cytotoxicity activity induced by these platinum(II) compounds against breast cancer (MDA-MB-231 and MCF-7), lung (A549), prostate (PC3), pancreas (BXPC-3), and normal peripheral blood mononuclear (PBMC) cells were evaluated by MTT assay. The cell viability MTT assay showed that complex (4) was more cytotoxic to all cancer cell lines tested and less cytotoxic against human PBMC. Therefore, complex (4) was selected to further investigate the mechanism of cytotoxic effects involved against MDA-MB-231 cell line (human triple-negative breast cancer). Sub-G1 analysis of the cell cycle showed that this complex induces cell death by apoptosis due to the cell loss of DNA content detected in flow cytometry. The cytotoxic effect induced by complex (4) was associated with the capability of the complex to induce mitochondrial membrane depolarization, as well as increase ROS levels and caspase activation, as a result of the activation of both extrinsic and intrinsic apoptosis pathways. Ultrastructural alterations were observed using scanning and transmission electron microscopy (SEM and TEM), such as membrane blebbing, filopodia reduction, empty mitochondrial matrix, and DNA fragmentation. Furthermore, complex (4) was tested in an MDA-MB-231 tumor nodule xenograft murine model and demonstrated a remarkable reduction in tumor size in BALB/c nude mice, when compared to the control animals.
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The canine corpus luteum (CL) is able to synthetise, activate and deactivate 17b-estradiol (E2) and also expresses nuclear estrogen receptors in a time-dependent manner during diestrus. Nevertheless, we are still missing a better comprehension of E2 functions in the canine CL, especially regarding the specific roles of estrogen receptor alpha (ERa) and ERb, encoded by ESR1 and 2, respectively. For that purpose, we analyzed transcriptomic data of canine non-pregnant CL collected on days 10, 20, 30, 40, 50 and 60 of diestrus and searched for differentially expressed genes (DEG) containing predicted transcription factor binding sites (TFBS) for ESR1 or ESR2. Based on biological functions of DEG presenting TFBS, expression of select transcripts and corresponding proteins was assessed. Additionally, luteal cells were collected across specific time points during diestrus and specificity of E2 responses was tested using ERa and/or ERb inhibitors. Bioinformatic analyses revealed 517 DEGs containing TFBS, from which 67 for both receptors. In general, abundance of predicted ESR1 targets was greater in the beginning, while abundance of ESR2 targets was greater in the end of diestrus. ESR1/ESR2 ratio shifted from an increasing to a decreasing pattern from day 30 to 40 post ovulation. Specific receptor inhibition suggested an ERa-mediated positive regulation of CL function at the beginning of diestrus and an ERb-mediated effect contributing to luteal regression. In conclusion, our data points toward a broad spectrum of action of E2 and its nuclear receptors, which can also act as transcription factors for other genes regulating canine CL function.
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INTRODUCTION: Technology arrives aiming at bringing benefits to society, with aspects applied to health such as Information and Communication Technologies (ICTs). Developing a technology solution requires methodological rigor and systematic instructional design. METHOD: This experience report method used the Agile methodology for management and control of results in the development of Information and Communication Technologies. RESULTS: The Agile methodology was adopted using the Scrum framework, involving people, artifacts, and ceremonies. The Scrum team was consisted of multidisciplinary professionals and undergraduate students. Artifacts are comprised of product backlog, sprints, sprint backlog, time-box, ready concept, and release burn-down. CONCLUSIONS: The adoption of the Scrum methodology helps with the integration of roles and knowledge to a project. Moreover, it efficiently helps carrying out activities by allowing careful analysis of each stage with regard to quality, technology, and implementation.
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Estudos Interdisciplinares , HumanosRESUMO
AIMS: Sepsis is a potentially fatal systemic inflammatory response and its underlying pathophysiology is still poorly understood. Studies suggest that obesity, a component of metabolic syndrome (MS), is associated with sepsis survival. Therefore, this study focused on investigating the influence of MS on mortality and cardiovascular dysfunction induced by sublethal cecal ligation and puncture (SL-CLP). MAIN METHODS: Newborn Swiss mice received monosodium glutamate (MSG) (4 mg kg-1 day-1, s.c.) during the first 5 d of life for MS induction, while the control pups received equimolar saline solution. On the 75th day, SL-CLP was used to induce mild sepsis (M-CLP) in the MS (MS-M-CLP) and control (SAL-M-CLP) mice. The effect of MS on sepsis in mice was assessed by determining the survival rate and quantification of nitric oxide (NO) in the plasma, and associating this data with hematological and cardiovascular parameters. KEY FINDINGS: MS improved the survival of septic mice, preventing impairment to hematological and cardiovascular parameters. In addition, MS attenuated plasmatic NO increase, which is a typical feature of sepsis. SIGNIFICANCE: These findings provide new insights into the relationship between obesity and mild sepsis in mice, thus revealing an approach in favor of the "obesity paradox."