Effect of cyclosporin-A on the blood--retinal barrier permeability in streptozotocin-induced diabetes.

BACKGROUND: Our previous results showed that in retinas from streptozotocin (STZ)-induced diabetic rats there is an increased level of interleukin-1beta (IL-1beta). This cytokine may be involved in the expression of the inducible isoform of the nitric oxide synthase (iNOS), with consequent synthesis of large amounts of NO and blood-retinal barrier (BRB) breakdown. AIMS: The aim of this work was to examine whether the administration of cyclosporin-A (Cs-A) to STZ-induced diabetic rats inhibits the synthesis of IL-1beta and the expression of the inducible proteins, iNOS and cyclo-oxygenase-2 (COX-2) in retinal cells, and whether the activity of these proteins contribute to BRB breakdown. METHODS: The level of IL-1beta was evaluated by ELISA and the NO production by L-[3H]-citrulline formation. Expression of iNOS and COX-2 proteins was determined by two methods, western blot and immunohistochemistry. The permeability of the BRB was assessed by quantification of the vitreous protein. RESULTS AND DISCUSSION: Our results indicated that the levels of IL-1beta and NO in retinas from Cs-A-treated diabetic rats are significantly reduced, as compared to that in non-treated diabetic rats. The treatment of diabetic rats with Cs-A also significantly inhibited the expression of the inducible proteins, iNOS and COX-2. The evaluation of the vitreous protein content revealed that Cs-A also reduces the BRB permeability. Taken together, these results suggest that the increased production of the inflammatory mediators, IL-1beta and NO, in diabetes may affect the BRB permeability and therefore contribute to the development of diabetic retinopathy

Development of an FIA system with amperometric detection for determination of bentazone in estuarine waters

On the basis of its electrochemical behaviour a new flow-injection analysis (FIA) method with amperometric detection has been developed for quantification of the herbicide bentazone (BTZ) in estuarine waters. Standard solutions and samples (200 µL) were injected into a water carrier stream and both pH and ionic strength were automatically adjusted inside the manifold. Optimization of critical FIA conditions indicated that the best analytical results were obtained at an oxidation potential of 1.10 V, pH 4.5, and an overall flow-rate of 2.4 mL min–1. Analysis of real samples was performed by means of calibration curves over the concentration range 2.5x10–6 to 5.0x10–5 mol L–1, and results were compared with those obtained by use of an independent method (HPLC). The accuracy of the amperometric determinations was ascertained; errors relative to the comparison method were below 4% and sampling rates were approximately 100 samples h–1. The repeatability of the proposed method was calculated by assessing the relative standard deviation (%) of ten consecutive determinations of one sample; the value obtained was 2.1%

Firefighters’ Occupational Exposure in Preparation for Wildfire Season: Addressing Biological Impact

The characterization of wildland firefighters' occupational exposure must consider different exposures, including those at the fire station. The present study aimed to characterize the occupational exposure of 172 Northern Portuguese wildland firefighters in fire stations during the pre-wildfire season of 2021. The biological impact of estimated inhaled doses of PM10 and PM2.5 (indoor/outdoor) was accessed through a buccal micronucleus cytome (BMCyt) assay in exfoliated buccal cells of a subgroup of 80 firefighters. No significant association was found between estimated inhaled doses of PM10 and PM2.5 (mean 1.73 +/- 0.43 mu g kg-1 and 0.53 +/- 0.21 mu g kg-1, respectively) and biological endpoints. However, increased frequencies of cell death parameters were found among subjects of the Permanent Intervention Teams (full-time firefighters). The intake of nutritional supplements was associated with a significant decrease in micronucleus frequencies (i.e., DNA damage or chromosome breakage). In addition, our findings showed a significantly increased frequency of cell death endpoints (i.e., nuclear fragmentation) with coffee consumption, while daily consumption of vegetables significantly decreased it (i.e., nuclear shrinkage). Our results provide data on the occupational exposure of wildland firefighters while working in fire stations during the pre-wildfire season, providing the essential baseline for further studies throughout the wildfire season.This work received financial support from the project PCIF/SSO/0017/2018 (http:// doi.org/10.54499/PCIF/SSO/0017/2018) by the Fundação para a Ciência e a Tecnologia (FCT), Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through national funds. Filipa Esteves, the PhD grant UI/BD/150783/2020 recipient, is supported by FCT and the European Social Fund (ESF). This work is financed by national funds through the FCT within the scope of projects UIDB/04750/2020 (http://doi.org/10.54499/UIDB/04750/2020) and LA/P/0064/2020 (http://doi.org/10.54499/LA/P/0064/2020), LA/P/0045/2020 (http://doi.org/10.54499/LA/P/ 0045/2020), UIDP/00511/2020 (http://doi.org/10.54499/UIDP/00511/2020) and UIDB/00511/2020 (http://doi.org/10.54499/UIDB/00511/2020), LA/P/0008/2020 (http://doi.org/10.54499/LA/P/ 0008/2020), UIDP/50006/2020 (http://doi.org/10.54499/UIDP/50006/2020) and UIDB/50006/2020 (http://doi.org/10.54499/UIDB/50006/2020).info:eu-repo/semantics/publishedVersio

Caracterização fenotípica e genética de cepas de Bordetella pertussis isoladas em São Paulo, Brasil, 1988-2002

Whooping cough or pertussis was a major cause of childhood morbidity and mortality in the world until the introduction of a whole-cell vaccine in the 1940's. However, since the early 1980's whooping cough cases have increased in many countries, becoming an important problem of public health. This increase may be due to accuracy of laboratory diagnosis and reporting of the disease, a decline in immunity over time, demographic changes, and adaptation of the bacterial population to vaccine-induced immunity. The purpose of this study was to analyze phenotypically and genotypically a collection of 67 Bordetella pertussis isolates recovered during the period 1988-2002 in São Paulo State, Brazil to determine their characteristics and relatedness. All isolates were submitted to susceptibility testing to erythromycin, serotyping, and 56 isolates were analyzed by Pulsed Field Gel Electrophoresis (PFGE). All isolates were susceptible to erythromycin and the majority of them belonged to serotype 1,3. The 56 isolates were classified into 11 PFGE profiles according to the differences in banding patterns. Although more than 60% of the isolates were recovered from patients aged less than three months, almost 15% of them were isolated from adolescents/adults evidencing the increase in the incidence of pertussis among this group of age.A coqueluche ou pertussis foi a maior causa de morbidade e mortalidade infantil em todo o mundo até a introdução de uma vacina na década de 1940. Entretanto, desde a década de 1980, a coqueluche tornou-se, em muitos países , um importante problema de saúde pública. Este acontecimento pode ser atribuído à melhoria do diagnóstico laboratorial e da notificação da doença, declínio da imunidade no decorrer do tempo, mudanças demográficas ou adaptação da população bacteriana à imunidade induzida pela vacina. O objetivo deste estudo foi analisar as características fenotípicas e genotípicas de uma coleção de 67 cepas de Bordetella pertussis isoladas no período 1988-2002 em São Paulo, Brasil. Todas as cepas foram submetidas à determinação do perfil de resistência à eritromicina, à sorotipagem e 56 cepas à eletroforese em campo pulsado (PFGE). Todas as cepas foram sensíveis à eritromicina e a maioria delas pertencia ao sorotipo 1,3. As 56 cepas foram classificadas em 11 perfis de PFGE com base nas diferenças no padrão de bandas. Embora mais de 60% das cepas tenham sido isoladas de crianças com menos de três meses de idade, cerca de 15% delas era de adolescentes/adultos evidenciando um aumento da incidência da coqueluche nesse grupo etário

Reuma.pt/vasculitis - the Portuguese vasculitis registry

BACKGROUND: The vasculitides are a group of rare diseases with different manifestations and outcomes. New therapeutic options have led to the need for long-term registries. The Rheumatic Diseases Portuguese Register, Reuma.pt, is a web-based electronic clinical record, created in 2008, which currently includes specific modules for 12 diseases and > 20,000 patients registered from 79 rheumatology centres. On October 2014, a dedicated module for vasculitis was created as part of the European Vasculitis Society collaborative network, enabling prospective collection and central storage of encrypted data from patients with this condition. All Portuguese rheumatology centres were invited to participate. Data regarding demographics, diagnosis, classification criteria, assessment tools, and treatment were collected. We aim to describe the structure of Reuma.pt/vasculitis and characterize the patients registered since its development. RESULTS: A total of 687 patients, with 1945 visits, from 13 centres were registered; mean age was 53.4 ± 19.3 years at last visit and 68.7% were females. The most common diagnoses were Behçet's disease (BD) (42.5%) and giant cell arteritis (GCA) (17.8%). Patients with BD met the International Study Group criteria and the International Criteria for BD in 85.3 and 97.2% of cases, respectively. Within the most common small- and medium-vessel vasculitides registered, median [interquartile range] Birmingham Vasculitis Activity Score (BVAS) at first visit was highest in patients with ANCA-associated vasculitis (AAV) (17.0 [12.0]); there were no differences in the proportion of patients with AAV or polyarteritis nodosa who relapsed (BVAS≥1) or had a major relapse (≥1 major BVAS item) during prospective assessment (p = 1.00, p = 0.479). Biologic treatment was prescribed in 0.8% of patients with GCA, 26.7% of patients with AAV, and 7.6% of patients with BD. There were 34 (4.9%) deaths reported. CONCLUSIONS: Reuma.pt/vasculitis is a bespoke web-based registry adapted for routine care of patients with this form of rare and complex diseases, allowing an efficient data-repository at a national level with the potential to link with other international databases. It facilitates research, trials recruitment, service planning and benchmarking.publishersversionpublishe

description of the methodological approach

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Photosynthesis by six portuguese maize cultivars during drought stress and recovery

Photosynthesis, chlorophyll fluorescence and leaf water parameters were measured in six Portuguese maize (Zea mays L.) cultivars during and following a period of drought stress. The leaf relative water content (RWC) responded differently among cultivars but, except for cultivar PB369, recovered close to initial values after watering was restored. Photosynthetic rate and stomatal conductance decreased with drought but more slowly in cultivars PB269 and PB260 than in cultivars AD3R, PB64, PB304 and PB369. Water use efficiency (WUE) decreased during the water stress treatment although with cultivar PB260 the decrease was marked only when the RWC fell below 40%. Recovery of WUE was seen with all cultivars except PB369. The maximum quantum efficiency of photosystem II, the photochemical quenching coefficient, the electron transport rate in PSII and the estimated functional plastoquinone pool tended to decrease with drought, while the non -photochemical quenching coefficient increased. The parameters estimated from chlorophyll fluorescence did not recover in PB369, during re - watering. The results show that PB260 and PB269 were the most tolerant and PB369 was the least tolerant cultivars to water stress. The variation found amongst the cultivars tested suggests the existence of valuable genetic resources for crop improvement in relation to drought tolerance

A small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic physiology in Alzheimer's disease

Publisher Copyright: Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.In Alzheimer's disease (AD), amyloid β (Aβ)-triggered cleavage of TrkB-FL impairs brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, and synaptic transmission and plasticity. Using cerebrospinal fluid and postmortem human brain samples, we show that TrkB-FL cleavage occurs from the early stages of the disease and increases as a function of pathology severity. To explore the therapeutic potential of this disease mechanism, we designed small TAT-fused peptides and screened their ability to prevent TrkB-FL receptor cleavage. Among these, a TAT-TrkB peptide with a lysine-lysine linker prevented TrkB-FL cleavage both in vitro and in vivo and rescued synaptic deficits induced by oligomeric Aβ in hippocampal slices. Furthermore, this TAT-TrkB peptide improved the cognitive performance, ameliorated synaptic plasticity deficits and prevented Tau pathology progression in vivo in the 5XFAD mouse model of AD. No evidence of liver or kidney toxicity was found. We provide proof-of-concept evidence for the efficacy and safety of this therapeutic strategy and anticipate that this TAT-TrkB peptide has the potential to be a disease-modifying drug that can prevent and/or reverse cognitive deficits in patients with AD.publishersversionpublishe