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1.
Pharmaceutics ; 14(9)2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36145662

RESUMO

Neurodegenerative diseases (NDD) have been of great interest to scientists for a long time due to their multifactorial character. Among these pathologies, Alzheimer's disease (AD) is of special relevance, and despite the existence of approved drugs for its treatment, there is still no efficient pharmacological therapy to stop, slow, or repair neurodegeneration. Existing drugs have certain disadvantages, such as lack of efficacy and side effects. Therefore, there is a real need to discover new drugs that can deal with this problem. However, as AD is multifactorial in nature with so many physiological pathways involved, the most effective approach to modulate more than one of them in a relevant manner and without undesirable consequences is through polypharmacology. In this field, there has been significant progress in recent years in terms of pharmacoinformatics tools that allow the discovery of bioactive molecules with polypharmacological profiles without the need to spend a long time and excessive resources on complex experimental designs, making the drug design and development pipeline more efficient. In this review, we present from different perspectives how pharmacoinformatics tools can be useful when drug design programs are designed to tackle complex diseases such as AD, highlighting essential concepts, showing the relevance of artificial intelligence and new trends, as well as different databases and software with their main results, emphasizing the importance of coupling wet and dry approaches in drug design and development processes.

2.
Health Place ; 77: 102869, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35932598

RESUMO

Ultra-processed drinks (UPDs) consumption is increasing, and this intake has been associated with the risk of illness and death. Data on individuals (n = 430) and food stores (n = 231) were collected in an economically vulnerable area in Recife-Brazil, and multilevel regression models were applied to assess the association between UPDs consumption with food environment characteristics. The results show 29.5% of individuals consume UPDs, higher UPD consumption was significantly associated with age (OR: 0.96), lower educational levels (OR:2.06), high density of stores predominantly selling UPFs (OR:2.34) and lower availability of FV in stores (OR:0.49). The applied methodology can inform food environment interventions to reduce UPDs consumption.


Assuntos
Fast Foods , Populações Vulneráveis , Brasil , Humanos , Análise Multinível
3.
Animals (Basel) ; 12(12)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35739922

RESUMO

Antimicrobial peptides (AMP) play an essential role in the innate immune system, modulating the defense response. In a previous study, we demonstrated the antimicrobial activity of synthetic hepcidin (hep20) from rainbow trout (Oncorhynchus mykiss), and its protective effect in European sea bass (Dicentrarchus labrax) challenged with Vibrio anguillarum. Additionally, we described the uptake and distribution of hep20 in different tissues and leukocyte cells. Interestingly, various AMPs characterized in high vertebrates, called host defense peptides (HDPs), also possess immunomodulation activity. For that reason, the present study explores the immunomodulatory abilities of hep20 through in vitro and in vivo studies. First, a monocyte/macrophage RTS-11 cell line from rainbow trout was used to evaluate hep20 effects on pro- and anti-inflammatory cytokines in fish leukocyte cells. Next, the European sea bass juveniles were used to determine if hep20 can regulate the expression of cytokines in fish immune tissues. The results show that hep20 was uptake inner to RTS-11 cells and was able to induce the expression of IL-10, IL-1ß, and TNFα at transcriptional and protein levels. Then, the European sea bass juveniles were given intraperitoneal injections of the peptide. At 1, 3, 7, 14, and 21 days post-injection (dpi), IL-10, IL -1ß, and TNFα mRNA were quantified in the anterior gut, spleen, and head kidney. The hep20 was able to up-regulate cytokine gene expression in these tissues, mainly in the head kidney. Furthermore, the evaluated cytokines showed a cyclical tendency of higher to lesser expression. Finally, a bioinformatics analysis showed that the structure adopted by hep20 is similar to the γ-core domain described for cysteine-stabilized AMP, defined as immunomodulatory and antimicrobial, which could explain the ability of hep20 to regulate the cytokine expression. This study provides new insights into immunomodulatory function complementary to the previously established antimicrobial activity of hep20, suggesting a role as an HDP in teleost fish. These facts are likely to be associated with molecular functions underpinning the protective effect of fish hepcidin against pathogens.

4.
Animals (Basel) ; 12(9)2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35565600

RESUMO

A variety of long-term stress conditions may exist in fish cultivation, some of which are so severe that fish can no longer reestablish homeostasis. In teleost fish, the brain and gastrointestinal tract integrate signals that include the perception of stress factors regulating physiological responses, such as social stress by fish population density, where peripheral and central signals, such as peptide hormones, are the main regulators. Therefore, we proposed in this study to analyze the effect of different stock densities (SD) in the gene expression of brain neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP), together with the gastrointestinal peptide hormones leptin (Lep), vasointestinal peptide (VIP), and protachykinin-1 (Prk-1) in Salmo salar post-smolt. The coding sequence of S. salar VIP and Prk-1 precursors were firstly cloned and characterized. Then, the mRNA expression of these genes, together with the NPY, Lep, and CGRP genes, were evaluated in post-smolts kept at 11 Kg/m3, 20 Kg/m3, and 40 Kg/m3. At 14 days of culture, the brain CGRP and liver leptin mRNA levels increased three and tenfold in the post-smolt salmons kept at the highest SD, respectively. The high levels of leptin were kept during all the fish culture experiments. In addition, the highest expression of intestine VIP mRNA was obtained on Day 21 in the group of 40 Kg/m3 returning to baseline on Day 40. In terms of stress biochemical parameters, cortisol levels were increased in the 20 Kg/m3 and 40 Kg/m3 groups on Day 40 and were the highest in the 20 Kg/m3 group on Day 14. This study provides new insight into the gastrointestinal signals that could be affected by chronic stress induced by high stock density in fish farming. Thus, the expression of these peptide hormones could be used as molecular markers to improve production practices in fish aquaculture.

5.
Microb Pathog ; 166: 105539, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35447314

RESUMO

Sporotrichosis is a cosmopolitan mycosis caused by pathogenic species of Sporothrix genus, that in Brazil is often acquired by zoonotic transmission involved infected cats with S. brasiliensis. Previous studies showed that the Sporothrix spp. recombinant enolase (rSsEno), a multifunctional protein with immunogenic properties, could be a promising target for vaccination against sporotrichosis in cats. Nevertheless, the considerable sequence identity (62%) of SsEno with its feline counterpart is a great concern. Here, we report the identification in silico, chemical synthesis and biological validation of six peptides of SsEno with low sequence identity to its cat orthologue. All synthesized peptides exhibit B-cell epitopes on the molecular surface of SsEno and proved to be highly reactive with the serum of infected mice with S. brasiliensis and sera of cats with sporotrichosis. Interestingly, our study revealed that anti-peptide sera did not react with the recombinant enolase from Felis catus (cats, rFcEno), thus, may not trigger autoimmune response in these felines if used as a vaccine antigen. The immunization with peptide mixture (PeptMix) formulated with Freund adjuvant (FA), induced high levels of antigen-specific IgG, IgG1 and IgG2b antibodies that conferred protection upon passive transference in infected BALB/c mice with S. brasiliensis. We also observed, that the FA+PeptMix formulation induced a Th1/Th2/Th17 cytokine profile ex vivo, associated with protecting effect against the experimental sporotrichosis. Our results suggest that the six SsEno-derived peptides here evaluated, could be used as safe antigens for the development of vaccine strategies against feline sporotrichosis, whether prophylactic or therapeutic.


Assuntos
Vacinas Fúngicas , Fosfopiruvato Hidratase , Esporotricose , Animais , Brasil , Gatos , Epitopos , Vacinas Fúngicas/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/imunologia , Sporothrix/enzimologia , Sporothrix/genética , Esporotricose/prevenção & controle
6.
BMC Infect Dis ; 22(1): 124, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-35123414

RESUMO

BACKGROUND: Both CMV and Rubella virus infections are associated with the risk of vertical transmission, fetal death or congenital malformations. In Angola, there are no reports of CMV and Rubella studies. Therefore, our objectives were to study the seroprevalence of anti-CMV and anti-Rubella antibodies in pregnant women of Luanda (Angola), identify the risk of primary infection during pregnancy and evaluate the socio-demographic risk factors associated with both infections. METHODS: A prospective cross-sectional study was conducted from August 2016 to May 2017. Specific anti-CMV and anti-Rubella antibodies were quantified by electrochemiluminescence and demographic and clinical data were collected using standardized questionnaire. Bivariate and multivariate logistic regression analysis were used to quantify the effect of clinical and obstetric risk factors on virus seroprevalence. RESULTS: We recruited 396 pregnant women aged from 15 to 47. Among them, 335 (84.6%) were immune to both CMV and Rubella virus infections, while 8 (2.0%) had active CMV infection and 4 (1.0%) active RV infection but none had an active dual infection. Five women (1.2%) were susceptible to only CMV infection, 43 (10.9%) to only RV infection, and 1 (0.3) to both infections. Multivariate analysis showed a significant association between Rubella virus infection and number of previous births and suffering spontaneous abortion. CONCLUSIONS: Overall, this study showed that there is a high prevalence of anti-CMV and anti-Rubella antibodies in pregnant women in Luanda. It also showed that a small but important proportion of pregnant women, about 11%, are at risk of primary infection with rubella during pregnancy. This emphasizes the need for vaccination.


Assuntos
Complicações Infecciosas na Gravidez , Rubéola (Sarampo Alemão) , Idoso , Angola/epidemiologia , Anticorpos Antivirais , Estudos Transversais , Citomegalovirus , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Gestantes , Prevalência , Estudos Prospectivos , Rubéola (Sarampo Alemão)/epidemiologia , Estudos Soroepidemiológicos
7.
J Med Chem ; 65(2): 1585-1607, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-34978799

RESUMO

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease without any effective treatment. Protein TDP-43 is a pathological hallmark of ALS in both sporadic and familiar patients. Post-translational modifications of TDP-43 promote its aggregation in the cytoplasm. Tau-Tubulin kinase (TTBK1) phosphorylates TDP-43 in cellular and animal models; thus, TTBK1 inhibitors emerge as a promising therapeutic strategy for ALS. The design, synthesis, biological evaluation, kinase-ligand complex structure determination, and molecular modeling studies confirmed novel pyrrolopyrimidine derivatives as valuable inhibitors for further development. Moreover, compound 29 revealed good brain penetration in vivo and was able to reduce TDP-43 phosphorylation not only in cell cultures but also in the spinal cord of transgenic TDP-43 mice. A shift to M2 anti-inflammatory microglia was also demonstrated in vivo. Both these activities led to motor neuron preservation in mice, proposing pyrrolopyrimidine 29 as a valuable lead compound for future ALS therapy.


Assuntos
Esclerose Amiotrófica Lateral/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Animais , Encéfalo/metabolismo , Estudos de Casos e Controles , Humanos , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Fosforilação , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacocinética , Ratos , Ratos Wistar , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Distribuição Tecidual
8.
Int J Pharm ; 611: 121292, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34780927

RESUMO

The prevalence of chronic and acute wounds, as well as the complexity of their treatment represent a great challenge for health systems around the world. In this context, the development of bioactive wound dressings that release active agents to prevent infections and promote wound healing, appears as the most promising solution. In this work, we develop an antibacterial and biocompatible wound dressing material made from coaxial electrospun fibers of poly(styrene-co-maleic anhydride) and poly(vinyl alcohol) (PSMA@PVA). The coaxial configuration of the fibers consists of a shell of poly (styrene-co-maleic anhydride) containing a variable concentration of silver nanoparticles (AgNPs) 0.1-0.6 wt% as antibacterial agent, and a core of PVA containing 1 wt% allantoin as healing agent. The fibers present diameters between 0.72 and 1.7 µm. The release of Ag+ in a physiological medium was studied for 72 h, observing a burst release during the first 14 h and then a sustained and controlled release during the remaining 58 h. Allantoin release curves showed significant release only after 14 h. The meshes showed an antibacterial activity against Pseudomonas aeruginosa and Bacillus subtilis that correlates with the amount of AgNPs incorporated and the release rate of Ag+. Indeed, meshes containing 0.3 and 0.6 wt% of AgNPs showed a 99.99% inhibition against both bacteria. The adherence and cell viability of the meshes were evaluated in mouse embryonic fibroblasts NIH/3T3, observing a significant increase in cell viability after 72 h of incubation accompanied by a reduced adhesion of fibroblasts that decreased in the presence of the active agents. These results show that the material prepared here is capable of significantly promoting fibroblast cell proliferation but without strong adherence, which makes it an ideal material for wound dressings with non-adherent characteristics and with potential for wound healing.


Assuntos
Nanopartículas Metálicas , Álcool de Polivinil , Animais , Bandagens , Proliferação de Células , Fibroblastos , Maleatos , Anidridos Maleicos , Camundongos , Poliestirenos , Prata , Estireno
9.
Arq. bras. cardiol ; 118(2): 463-475, 2022. tab, graf
Artigo em Inglês, Português | LILACS | ID: biblio-1364328

RESUMO

Resumo Fundamento O remodelamento cardíaco patológico se caracteriza por disfunção diastólica e sistólica, levando à insuficiência cardíaca. Neste contexto, o cenário disfuncional do trânsito de cálcio miocárdico (Ca2+) tem sido pouco estudado. Um modelo experimental de estenose aórtica tem sido extensamente utilizado para aprimorar os conhecimentos sobre os principais mecanismos do remodelamento patológico cardíaco. Objetivo Entender o processo disfuncional dos principais componentes responsáveis pelo equilíbrio do cálcio miocárdico e sua influência sobre a função cardíaca na insuficiência cardíaca induzida pela estenose aórtica. Métodos Ratos Wistar de 21 dias de idade foram distribuídos em dois grupos: controle (placebo; n=28) e estenose aórtica (EaO; n=18). A função cardíaca foi analisada com o ecocardiograma, músculo papilar isolado e cardiomiócitos isolados. No ensaio do músculo papilar, SERCA2a e a atividade do canal de Ca2+ do tipo L foram avaliados. O ensaio de cardiomiócitos isolados avaliou o trânsito de cálcio. A expressão proteica da proteínas do trânsito de cálcio foi analisada com o western blot. Os resultados foram estatisticamente significativos quando p <0,05. Resultados Os músculos papilares e cardiomiócitos dos corações no grupo EaO demonstraram falhas mecânicas. Os ratos com EaO apresentaram menor tempo de pico do Ca2+, menor sensibilidade das miofibrilas do Ca2+, prejuízos nos processos de entrada e recaptura de cálcio pelo retículo sarcoplasmático, bem como disfunção no canal de cálcio do tipo L (CCTL). Além disso, os animais com EaO apresentaram maior expressão de SERCA2a, CCTL e trocador de Na+/Ca2+. Conclusão Insuficiência cardíaca sistólica e diastólica devido à estenose aórtica supravalvular acarretou comprometimento da entrada de Ca2+ celular e inibição da recaptura de cálcio pelo retículo sarcoplasmático devido à disfunção no CCTL e SERCA2a, assim como mudanças no trânsito de cálcio e na expressão das principais proteínas responsáveis pela homeostase de Ca2+ celular.


Abstract Background Maladaptive cardiac remodelling is characterized by diastolic and systolic dysfunction, culminating in heart failure. In this context, the dysfunctional scenario of cardiac calcium (Ca2+) handling has been poorly studied. An experimental model of aortic stenosis has been extensively used to improve knowledge about the key mechanisms of cardiac pathologic remodelling. Objective To understand the dysfunctional process of the major components responsible for Ca2+ balance and its influence on cardiac function in heart failure induced by aortic stenosis. Methods Male 21-day-old Wistar rats were distributed into two groups: control (sham; n= 28) and aortic stenosis (AoS; n= 18). Cardiac function was analysed by echocardiogram, isolated papillary muscle, and isolated cardiomyocytes. In the papillary muscle assay, SERCA2a and L-type Ca2+ channel activity was evaluated. The isolated cardiomyocyte assay evaluated Ca2+ handling. Ca2+ handling protein expression was analysed by western blot. Statistical significance was set at p <0.05. Results Papillary muscles and cardiomyocytes from AoS hearts displayed mechanical malfunction. AoS rats presented a slower time to the Ca2+ peak, reduced Ca2+ myofilament sensitivity, impaired sarcoplasmic reticulum Ca2+ influx and reuptake ability, and SERCA2a and L-type calcium channel (LTCC) dysfunction. Moreover, AoS animals presented increased expression of SERCA2a, LTCCs, and the Na+/Ca2+ exchanger. Conclusion Systolic and diastolic heart failure due to supravalvular aortic stenosis was paralleled by impairment of cellular Ca2+ influx and inhibition of sarcoplasmic reticulum Ca2+ reuptake due to LTCC and SERCA2a dysfunction, as well as changes in Ca2+ handling and expression of the major proteins responsible for cellular Ca2+ homeostasis.


Assuntos
Animais , Masculino , Ratos , Estenose da Valva Aórtica/patologia , Insuficiência Cardíaca/patologia , Músculos Papilares , Cálcio/metabolismo , Ratos Wistar , Miócitos Cardíacos/patologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Contração Miocárdica/fisiologia
10.
SSM Popul Health ; 16: 100982, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34926783

RESUMO

The study of premature deaths from causes that are generally preventable given the current availability of healthcare - called amenable deaths due to healthcare - provides information on the quality of services. However, they are not only impacted by healthcare characteristics: other factors are also likely to influence. Therefore, identifying the association between amenable deaths due to healthcare and health determinants, such as education, might be the key to preventing these deaths in the future. Still unclear however, is how this works and how amenable deaths due to healthcare are distributed and evolve within the European Union (EU) below the national level. We therefore studied the geographical and temporal patterns of amenable deaths due to healthcare in the 259 EU regions from 1999 to 2016, including the 2007-2008 financial crisis and the post-2008 economic downturn, and identified whether any association with education exists. A cross-sectional ecological study was carried out. Using a hierarchical Bayesian model, we estimated the average smoothed Standardized Mortality Ratios (sSMR). A regression model was also applied to measure the relative risks (RR) at 95% credible intervals for cause-specific mortality association with education. Results show that amenable deaths due to healthcare decreased globally. Nevertheless, the decrease is not the same across all regions, and inequalities within countries do persist, with lower mortality ratios seen in regions from Central European countries and higher mortality ratios in regions from Eastern European countries. Also, the evolution trend reveals that after the financial crisis, the number of these deaths increased in regions across almost all EU countries. Moreover, educational disparities in mortality emerged, and a statistical association was found between amenable deaths due to healthcare and early exit from education and training. These results confirm that identifying and understanding the background of regional differences may lead to a better understanding of the amenable deaths due to healthcare and allow for the application of more effective policies.

11.
Virol J ; 18(1): 239, 2021 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-34863183

RESUMO

BACKGROUND: HIV and HBV infections remain responsible for high rate of morbidity and mortality in many African Countries, affecting women and newborns. This study aims to analyze the spatial pattern of HIV and HBV infections in pregnant women in Luanda, Angola, and the statistical association between HIV and HBV and socio-economic characteristics, hygiene, and health status. METHODS: Detection of anti-HIV antibodies (total anti-HIV-1, anti-HIV-2 and HIV-1 p24 antigen) and Hepatitis B antigens (HBsAg, HBeAg) and antibodies (anti-HBc Total II, HBc IgM, Anti-HBsT II) was performed by Enzyme Linked Fluorescent Assay (ELFA) in serum samples of 878 pregnant women attended at the Lucrecia Paim Maternity Hospital (LPMH). Data were collected by questionnaire after written consent, and spatial distribution was assessed through a Kernel Density Function. The potential risk factors associated with HIV HBV infection were evaluated using bivariate and multivariate binomial logistic regression analysis. RESULTS: Anti-HIV antibodies were positive in 118 samples (13.4%) and HBV infection were positive in 226 (25.7%). The seroprevalence of HIV/HBV coinfection was of 6.3%. The results showed that the seroprevalence of HBV was similar in most municipalities: 25.8% in Belas; 26.6% in Viana; 27.6% in Luanda; 19.2% in Cacuaco; and 15.6% Cazenga. For HIV, the seroprevalence was also close ranges among the municipalities: 10.0% in Belas; 14.5% in Viana 14.9% in Luanda and 12.5% in Cazenga. However, the seroprevalence in municipality of in Cacuaco was lower (5.8%) and bivariate and multivariate analysis showed a lower risk for HIV in this area (OR 0.348, CI 0.083-0.986; OR 0.359, CI 0.085-1.021). The multivariate analysis had also showed a significant increased risk for HIV in women with 2 or 3 births (OR 1.860, CI 1.054-3.372). CONCLUSIONS: Our results underlined the need to improve the screening and clinical follow-up of HIV and HBV in Angola, as well the educational campaigns to prevent not only the morbidity and mortality associated with these diseases, but also their transmission, mainly in women in reproductive age and pregnant, encouraging the pre-natal consultations in order to avoid mother-to-child transmission.


Assuntos
Infecções por HIV , HIV-1 , Hepatite B , Complicações Infecciosas na Gravidez , Angola/epidemiologia , Feminino , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Gestantes , Prevalência , Estudos Soroepidemiológicos
12.
Artigo em Inglês | MEDLINE | ID: mdl-34444557

RESUMO

OBJECTIVE: To analyse the trends in chronic liver diseases and cirrhosis mortality, and the associated socioeconomic inequalities, in nine European cities and urban areas before and after the onset of the 2008 financial crisis. METHODS: This is an ecological study of trends in three periods of time: two before (2000-2003 and 2004-2008), and one after (2009-2014) the onset of the economic crisis. The units of analysis were the geographical areas of nine cities or urban areas in Europe. We analysed chronic liver diseases and cirrhosis standardised mortality ratios, smoothing them with a hierarchical Bayesian model by each city, area, and sex. An ecological regression model was fitted to analyse the trends in socioeconomic inequalities, and included the socioeconomic deprivation index, the period, and their interaction. RESULTS: In general, chronic liver diseases and cirrhosis mortality rates were higher in men than in women. These rates decreased in all cities during the financial crisis, except among men in Athens (rates increased from 8.50 per 100,000 inhabitants during the second period to 9.42 during the third). Socioeconomic inequalities in chronic liver diseases and cirrhosis mortality were found in six cities/metropolitan areas among men, and in four among women. Finally, in the periods studied, such inequalities did not significantly change. However, among men they increased in Turin and Barcelona and among women, several cities had lower inequalities in the third period. CONCLUSIONS: There are geographical socioeconomic inequalities in chronic liver diseases and cirrhosis mortality, mainly among men, that did not change during the 2008 financial crisis. These results should be monitored in the long term.


Assuntos
Recessão Econômica , Cirrose Hepática , Teorema de Bayes , Cidades , Feminino , Disparidades nos Níveis de Saúde , Humanos , Masculino , Mortalidade , Fatores Socioeconômicos , Espanha
13.
Electron. j. biotechnol ; 52: 13-20, July. 2021. tab, graf, ilus
Artigo em Inglês | LILACS | ID: biblio-1283173

RESUMO

BACKGROUND: In fish farming, the plant extracts containing antioxidant compounds have been added to the diet for enhancing pathogen resistance. In vitro studies evaluating the antioxidant effect of herbal extracts on fish cell models have focused on ROS production and the respiratory burst mechanism. However, the effects on enzymatic antioxidant defense on salmon leukocytes have not been evaluated. This study aims to evaluate the enzymatic antioxidant defense and ROS-induced cell damage in Salmon Head Kidney-1 (SHK-1) cell line exposed to polyphenol-enriched extract from Sambucus nigra flowers. RESULTS: Firstly, the Total Reactive Antioxidant Power (TRAP) assay of elderflower polyphenol (EP) was evaluated, showing 459 and 489 times more active than gallic acid and butyl hydroxy toluene (BHT), respectively. The toxic effect of EP on salmon cells was not significant at concentrations below 120 mg/ mL and no hemolysis activity was observed between 20 and 400 mg/mL. The treatment of SHK-1 cell line with EP decreased both the lipid peroxidation and protein oxidation induced by H2O2, which could be associated with decreasing oxidative stress in the SHK-1 cells since the GSH/GSSG ratio increased when only EP was added. CONCLUSIONS: These results suggest that plant extracts enriched with polyphenols could improve the enzymatic antioxidant defense of salmon leukocytes and protect the cells against ROS-induced cell damage


Assuntos
Salmão , Extratos Vegetais/farmacologia , Sambucus nigra/química , Polifenóis/farmacologia , Peroxidação de Lipídeos , Sequestradores de Radicais Livres , Espécies Reativas de Oxigênio , Aquicultura , Estresse Oxidativo , Salmo salar , Resistência à Doença , Leucócitos , Antioxidantes
14.
J Aging Stud ; 57: 100938, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34083005

RESUMO

While the government responses to the COVID-19 pandemic have varied across the globe, there has been a unifying cry from academia and public health professionals warning of the detrimental effects of attaching our understanding of this new threat to our already ageist attitudes. What is inescapable is that COVID-19 has an age-related risk component and the latest data shows that risks start to rise for people from midlife onwards. As governance agencies, professional practice, and academia work towards assessing, communicating, and addressing this risk, we ask: are existing gerontological conceptualisations of ageism appropriate for this exceptional situation and what is being (re)produced in terms of an aged subjectivity? Following van Dyk's (2016) critique of gerontology's 'othering' through both 'glorification' (third age) and 'abjection' (fourth age), a content analysis of statements and policy documents issued in response to COVID-19 provides evidence of well-meaning and inadvertent ageism through homogenizing language, the abjection/glorification binary within 'old age', and the power binary constructed between age and an age-neutral midlife. The paper concludes with reflections on future directions for ageism research beyond COVID-19.


Assuntos
Etarismo/psicologia , Etarismo/estatística & dados numéricos , COVID-19/psicologia , Defesa do Consumidor/psicologia , Defesa do Consumidor/estatística & dados numéricos , Geriatria , Idoso , Humanos , Pandemias , SARS-CoV-2
15.
Dev Comp Immunol ; 123: 104163, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34118278

RESUMO

α-Enolase is an enzyme of the glycolytic pathway that has also been involved in vertebrate inflammatory processes through its interaction with plasminogen. However, its participation in the immune response of lower vertebrates during early life development is unknown. Opportunistic pathogens in salmon farming are the principal cause of mortality in the fry stage. For that reason, molecular indicators of their immunological status are required to ensure the success of the large-scale cultivation. Thus, the objective of this work was to analyze if ENO-1 is involved in the immune response of rainbow trout fry. For this purpose, the coding sequence of trout ENO-1 was characterized, identifying the plasminogen-binding domain that has been described for homologs of this enzyme in higher vertebrates. A peptide-epitope of α-enolase was used for producing mice antiserum. The specificity of polyclonal antibodies was confirmed by dot blot, ELISA and Western blot. Then, the antiserum was used to evaluate α-enolase expression in fry between 152 and 264 degree-days post-hatching after 2, 8, and 12 h of challenge with lipopolysaccharide from Pseudomona auroginosa. The expression of α-enolase at both transcriptional (RT-qPCR) and protein (ELISA) levels was significantly increased after 8 h post-challenge with lipopolysaccharide. These results were confirmed by proteomic analysis by 2D-difference gel electrophoresis (DIGE). This work provides the first evidence of the involvement of α-enolase in the early immune response of salmonids. Future research will be required to understand the possible interaction of α-enolase with plasminogen in cells and tissues of the salmonid immune system.


Assuntos
Biomarcadores/metabolismo , Proteínas de Peixes/metabolismo , Oncorhynchus mykiss/imunologia , Fosfopiruvato Hidratase/metabolismo , Animais , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Imunidade Inata , Lipopolissacarídeos/imunologia , Fosfopiruvato Hidratase/genética , Plasminogênio/metabolismo , Proteômica
16.
Biotechnol Prog ; 37(5): e3182, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34115926

RESUMO

Aedes aegypti is a mosquito vector of arboviruses such as dengue, chikungunya, zika and yellow fever that cause important public health diseases. The incidence and gravity of these diseases justifies the search for effective measures to reduce the presence of this vector in the environment. Bioinsecticides are an effective alternative method for insect control, with added ecological benefits such as biodegradability. The current study demonstrates that a chitinolytic enzyme complex produced by the fungus Trichoderma asperellum can disrupt cuticle formation in the L3 larvae phase of A. aegypti, suggesting such biolarvicidal action could be used for mosquito control. T. asperellum was exposed to chitin from different sources. This induction of cell wall degrading enzymes, including chitinase, N-acetylglucosaminidase and ß-1,3-glucanase. Groups of 20 L3 larvae of A. aegypti were exposed to varying concentrations of chitinolytic enzymes induced with commercial chitin (CWDE) and larvae cell wall degrading enzymes (L-CWDE). After 72 h of exposure to the CWDE, 100% of larvae were killed. The same percent mortality was observed after 48 h of exposure to L-CWDE at half the CWDE enzyme mixture concentration. Exoskeleton deterioration was further observed by scanning and electron microscopy. Our findings indicate that L-CWDE produced by T. asperellum reflect chitinolytic enzymes with greater specificity for L3 larval biomolecules. This specificity is characterized by the high percentage of mortality compared with CWDE treatments and also by abrupt changes in patterns of the cellular structures visualized by scanning and transmission electron microscopy. These mixtures of chitinolytic enzymes could be candidates, as adjuvant or synergistic molecules, to replace conventional chemical insecticides currently in use.


Assuntos
Aedes/efeitos dos fármacos , Hypocreales/enzimologia , Inseticidas , Larva/efeitos dos fármacos , Animais , Parede Celular/metabolismo , Quitina/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/farmacologia , Inseticidas/química , Inseticidas/farmacologia
17.
Dev Comp Immunol ; 124: 104182, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34166719

RESUMO

Chemokines such as IL-8 are part of an important group of proinflammatory response molecules, as well as cell recruitment. However, it has been described in both higher vertebrates and fish that IL-8 has an additional functional role by acting as an antimicrobial effector, either directly or by cleavage of a peptide derived from its C-terminal end. Nevertheless, it is still unknown whether this fragment is released in the context of infection by bacterial pathogens and if it could be immunodetected in tissues of infected salmonids. Therefore, the objective of this research was to demonstrate that the C-terminal end of IL-8 from Oncorhynchus mykiss is cleaved, retaining its antibacterial properties, and that is detectable in tissues of infected rainbow trout. SDS-PAGE and mass spectrometry demonstrated the cleavage of a fragment of about 2 kDa when the recombinant IL-8 was subjected to acidic conditions. By chemical synthesis, it was possible to synthesize this fragment called omIL-8α80-97 peptide, which has antibacterial activity against Gram-negative and Gram-positive bacteria at concentrations over 10 µM. Besides, by fluorescence microscopy, it was possible to locate the omIL-8α80-97 peptide both on the cell surface and in the cytoplasm of the bacteria, as well as inside the monocyte/macrophage-like cell. Finally, by indirect ELISA, Western blot, and mass spectrometry, the presence of the fragment derived from the C-terminal end of IL-8 was detected in the spleen of trout infected with Piscirickettsia salmonis. The results reported in this work present the first evidence about the immunodetection of an antibacterial, and probably cell-penetrating peptide cleaved from the C-terminal end of IL-8 in monocyte/macrophage-like cell and tissue of infected rainbow trout.


Assuntos
Peptídeos Antimicrobianos/metabolismo , Infecções Bacterianas/veterinária , Doenças dos Peixes/imunologia , Interleucina-8/metabolismo , Oncorhynchus mykiss/imunologia , Aeromonas salmonicida/efeitos dos fármacos , Aeromonas salmonicida/fisiologia , Animais , Peptídeos Antimicrobianos/síntese química , Peptídeos Antimicrobianos/farmacologia , Infecções Bacterianas/imunologia , Hidrólise , Imunidade Inata , Macrófagos/metabolismo , Macrófagos/microbiologia , Piscirickettsia/fisiologia , Proteínas Recombinantes/metabolismo , Baço/imunologia , Distribuição Tecidual/imunologia
18.
J Urban Health ; 98(4): 516-531, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33844122

RESUMO

Epidemiological studies on the impact of determining environmental factors on human health have proved that temperature extremes and variability constitute mortality risk factors. However, few studies focus specifically on susceptible individuals living in Portuguese urban areas. This study aimed to estimate and assess the health burden of temperature-attributable mortality among age groups (0-64 years; 65-74 years; 75-84 years; and 85+ years) in Lisbon Metropolitan Area, from 1986-2015. Non-linear and delayed exposure-lag-response relationships between temperature and mortality were fitted with a distributed lag non-linear model (DLNM). In general, the adverse effects of cold and hot temperatures on mortality were greater in the older age groups, presenting a higher risk during the winter season. We found that, for all ages, 10.7% (95% CI: 9.3-12.1%) deaths were attributed to cold temperatures in the winter, and mostly due to moderately cold temperatures, 7.0% (95% CI: 6.2-7.8%), against extremely cold temperatures, 1.4% (95% CI: 0.9-1.8%). When stratified by age, people aged 85+ years were more burdened by cold temperatures (13.8%, 95% CI: 11.5-16.0%). However, for all ages, 5.6% of deaths (95% CI: 2.7-8.4%) can be attributed to hot temperatures. It was observed that the proportion of deaths attributed to exposure to extreme heat is higher than moderate heat. As with cold temperatures, people aged 85+ years are the most vulnerable age group to heat, 8.4% (95% CI: 3.9%, 2.7%), and mostly due to extreme heat, 1.3% (95% CI: 0.8-1.8%). These results provide new evidence on the health burdens associated with alert thresholds, and they can be used in early warning systems and adaptation plans.


Assuntos
Temperatura Baixa , Calor Extremo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Temperatura Alta , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Mortalidade , Portugal/epidemiologia , Temperatura , Adulto Jovem
19.
J Water Health ; 19(2): 306-321, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33901026

RESUMO

The present work evaluated the surveillance of the drinking water quality information system database and correlated the findings of the microbiological analysis with the distribution of intestinal protozoa from the metropolitan region of Rio de Janeiro. From the database, we obtained 1,654 georeferenced monitoring stations that were used in the analysis. The results indicate that the minimum number of samples collected per parameter (free residual chlorine, turbidity, counts of total and fecal coliforms (Escherichia coli)) was not fulfilled, the collection of samples throughout the year was irregular and the representability of sampling points considered strategic was low (48% of municipalities). Besides, municipalities with a high prevalence for intestinal parasite protozoa were also the ones that had the highest counts for coliforms and the reverse can also be observed, indicating a transmission through contaminated drinking water. Despite the increased participation of municipalities in water surveillance actions during the studied period, it is necessary to implement managerial measures to improve the system, aiming to correct flaws and inconsistencies in the application of the water quality monitoring protocol.


Assuntos
Água Potável , Qualidade da Água , Animais , Cloro/análise , Escherichia coli , Microbiologia da Água , Abastecimento de Água
20.
Artigo em Inglês | MEDLINE | ID: mdl-33573190

RESUMO

In 2006, a policy reform restructured the maternal and perinatal healthcare system, including closing smaller maternity units, to further improve care in Portugal. This study aimed to investigate the effects of the 2006 National Program of Maternal and Neonatal Health policy on spatial inequalities in access to care and consequently avoidable infant mortality. A thematic analysis of qualitative data including interviews and surveys and a quantitative spatial analysis using Geographic Information Systems was applied. Spatial inequalities were found which may lead to avoidable infant mortality. Inequalities exist in freedom of choice and autonomy in care, within a medicalized system. Changes in approach to and organization of care would further enhance equitable spatial access to care in maternal health and reduce avoidable infant mortality.


Assuntos
Mortalidade Infantil , Saúde Materna , Feminino , Humanos , Lactente , Políticas , Portugal/epidemiologia , Gravidez
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