Endocrine disruptive action of diclofenac and caffeine on Astyanax altiparanae males (Teleostei: Characiformes: Characidae)

Diclofenac (DCF) and caffeine (CAF) are persistent pharmaceuticals that occur in mixtures in the aquatic ecosystems causing effects in the reproductive physiology of aquatic organisms. This study evaluated the physiological reproductive responses of Astyanax altiparanae males exposed to nominal concentrations of DCF (3.08 mg L− 1) and CAF (9.59 mg L− 1) separately and combined, for 96 h. The steroids profile, estrogenic biomarker vitellogenin (vtgA), testes and liver morphology, and also mortality of males were assessed. DCF and CAF degradation was 5% of the initial concentration for 24 h. The LC50 of the DCF and CAF were 30.8 mg L− 1 and 95.9 mg L− 1, respectively. Males exposed to DCF and CAF exhibited a reduction of 17β-Estradiol (E2) concentration compared to control (CTL). Similarly, testosterone (T) was also reduced in the DCF treatment, but this response was not observed in 11-Ketotestosterone (11-KT). Males exposed to DCF + CAF combined did not exhibit differences in T, E2 and 11-KT steroids. The vtgA gene expression and the sperm concentration did not change among the treatments. Moreover, acute exposure revealed a hypertrophy of hepatocytes cells in the DCF and DCF + CAF treatments. In conclusion, DCF and CAF, isolated, exhibit an endocrine disruptive activity in A. altiparanae male, an opposite response observed with the mixture of both compounds that abolishes the endocrine disruptive effects. DCF seems to be more toxic for this species, altering also hepatocytes morphology.Fil: Godoi, Filipe G.A.. Universidade de Sao Paulo; BrasilFil: Muñoz Peñuela, Marcela. Universidade de Sao Paulo; BrasilFil: Olio Gomes, Aline D.. Universidade de Sao Paulo; BrasilFil: Tolussi, Carlos E.. Universidade Anhembi-Morumbi; BrasilFil: Brambila Souza, Gabriela. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Branco, Giovana S.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Lo Nostro, Fabiana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Moreira, Renata. Universidade de Sao Paulo; Brasi

Genomics and epidemiology for gastric adenocarcinomas (GE4GAC): a Brazilian initiative to study gastric cancer

Abstract Gastric cancer (GC) is the fifth most common type of cancer worldwide with high incidences in Asia, Central, and South American countries. This patchy distribution means that GC studies are neglected by large research centers from developed countries. The need for further understanding of this complex disease, including the local importance of epidemiological factors and the rich ancestral admixture found in Brazil, stimulated the implementation of the GE4GAC project. GE4GAC aims to embrace epidemiological, clinical, molecular and microbiological data from Brazilian controls and patients with malignant and pre-malignant gastric disease. In this letter, we summarize the main goals of the project, including subject and sample accrual and current findings

Disfunção do trato urinário inferior: um diagnóstico comum na prática pediátrica

Disfunção do trato urinário inferior indica uma função anormal do trato urinário inferior para a idade da criança, que pode levar à perda da capacidade coordenada de armazenamento e eliminação de urina. É uma entidade comum em crianças, embora subdiagnosticada na prática clínica, e que, além de representar um risco para o trato urinário superior, causa um constrangimento emocional aos pais e às crianças, devido à incontinência urinária e à frustração em lidar com o problema. A aquisição da continência urinária diurna ocorre na maioria das crianças até os 4 anos e a noturna até os 5 anos de idade. Após esta idade, a incontinência urinária torna-se um problema social. Apesar da importância clínica, muitas vezes, os pais desconhecem os sintomas dessa disfunção. Esse artigo tem como objetivo abordar os principais aspectos relacionados ao diagnóstico dessa disfunção

Disfunção do trato urinário inferior: um diagnóstico comum na prática pediátrica Lower urinary tract dysfunction: a common diagnosis in the pediatrics practice

Disfunção do trato urinário inferior indica uma função anormal do trato urinário inferior para a idade da criança, que pode levar à perda da capacidade coordenada de armazenamento e eliminação de urina. É uma entidade comum em crianças, embora subdiagnosticada na prática clínica, e que, além de representar um risco para o trato urinário superior, causa um constrangimento emocional aos pais e às crianças, devido à incontinência urinária e à frustração em lidar com o problema. A aquisição da continência urinária diurna ocorre na maioria das crianças até os 4 anos e a noturna até os 5 anos de idade. Após esta idade, a incontinência urinária torna-se um problema social. Apesar da importância clínica, muitas vezes, os pais desconhecem os sintomas dessa disfunção. Esse artigo tem como objetivo abordar os principais aspectos relacionados ao diagnóstico dessa disfunção.Lower urinary tract dysfunction indicates an abnormal function of the lower urinary tract to the child's age, which can lead to loss of coordinated capacity storage and elimination of urine. It is a common entity in children, although under-diagnosed in clinical practice, and that, besides representing a risk to the upper urinary tract, causes an emotional embarrassment to parents and children, due to urinary incontinence and frustration in dealing with the problem. The acquisition of daytime urinary continence occurs in most children until age 4 and night, until 5 years of age. After this age, urinary incontinence becomes a social problem. Despite the clinical importance often parents are unaware of the symptoms of this dysfunction. This article aims to address the key issues related to the diagnosis of this dysfunction

Long-Chain Polyunsaturated Fatty Acids n−3 (n−3 LC-PUFA) as Phospholipids or Triglycerides Influence on <i>Epinephelus marginatus</i> Juvenile Fatty Acid Profile and Liver Morphophysiology

Phospholipids (PL) are membrane components composed of fatty acids (FA), while triglycerides (TG) are a main source of energy and essential FA. Polyunsaturated FA (PUFA), such as docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), are essential for marine carnivorous fish; thus, an 8-week experiment was performed to evaluate the influence of DHA and EPA, provided as PL and TG, on the morphophysiology of Epinephelus marginatus juveniles. A basal diet was manufactured, and DHA and EPA in PL form (PL1—low amount PL2—high amount) and TG form (TG1—low amount; TG2—high amount) were added. Dusky grouper juveniles were equally distributed in 12 tanks of 20 animals each, and liver and muscle were sampled for metabolic analysis. The total hepatic lipids in PL1 and PL2 were higher when compared to the initial, TG1 and TG2 groups. Total lipids in muscle were higher in PL2 and TG1 than PL1 and TG2, respectively. Diets rich in DHA and EPA in PL and TG resulted in higher deposition of these FA in the muscle polar fraction. However, fish fed diets containing lower amounts of DHA and EPA in PL and TG stored those in the muscle neutral fraction and liver, centralizing the storage of DHA and EPA

Gonadotropin subunits of the characiform Astyanax altiparanae : Molecular characterization, spatiotemporal expression and their possible role on female reproductive dysfunction in captivity

To better understand the endocrine control of reproduction in Characiformes and the reproductive dysfunctions that commonly occur in migratory fish of this order when kept in captivity, we chose Astyanax altiparanae, which has asynchronous ovarian development and multiple spawning events, as model species. From A. altiparanae pituitary total RNA, we cloned the full-length cDNAs coding for the follicle-stimulating hormone β subunit (fshb), the luteinizing hormone β subunit (lhb), and the common gonadotropin α subunit (gpha). All three sequences showed the highest degree of amino acid identity with other homologous sequences from Siluriformes and Cypriniformes. Real-time, quantitative PCR analysis showed that gpha, fshb and lhb mRNAs were restricted to the pituitary gland. In situ hybridization and immunofluorescence, using specific-developed and characterized polyclonal antibodies, revealed that both gonadotropin β subunits mRNAs/proteins are expressed by distinct populations of gonadotropic cells in the proximal pars distalis. No marked variations for lhb transcripts levels were detected during the reproductive cycle, and 17α,20β-dihydroxy-4-pregnen-3-one plasma levels were also constant, suggesting that the reproductive dysfunction seen in A. altiparanae females in captivity are probably due to a lack of increase of Lh synthesis during spawning season. In contrast, fshb transcripts changed significantly during the reproductive cycle, although estradiol-17β (E2) levels remained constant during the experiment, possibly due to a differential regulation of E2 synthesis. Taken together, these data demonstrate the putative involvement of gonadotropin signaling on the impairment of the reproductive function in a migratory species when kept in captivity. Future experimental studies must be carried to clarify this hypothesis. All these data open the possibility for further basic and applied studies related to reproduction in this fish model

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p&lt;0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p&lt;0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status