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1.
Nature ; 579(7799): 427-432, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32132707

RESUMO

In mammalian cells, mitochondrial dysfunction triggers the integrated stress response, in which the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) results in the induction of the transcription factor ATF41-3. However, how mitochondrial stress is relayed to ATF4 is unknown. Here we show that HRI is the eIF2α kinase that is necessary and sufficient for this relay. In a genome-wide CRISPR interference screen, we identified factors upstream of HRI: OMA1, a mitochondrial stress-activated protease; and DELE1, a little-characterized protein that we found was associated with the inner mitochondrial membrane. Mitochondrial stress stimulates OMA1-dependent cleavage of DELE1 and leads to the accumulation of DELE1 in the cytosol, where it interacts with HRI and activates the eIF2α kinase activity of HRI. In addition, DELE1 is required for ATF4 translation downstream of eIF2α phosphorylation. Blockade of the OMA1-DELE1-HRI pathway triggers an alternative response in which specific molecular chaperones are induced. The OMA1-DELE1-HRI pathway therefore represents a potential therapeutic target that could enable fine-tuning of the integrated stress response for beneficial outcomes in diseases that involve mitochondrial dysfunction.


Assuntos
Citosol/metabolismo , Metaloendopeptidases/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Proteínas Mitocondriais/metabolismo , Estresse Fisiológico , eIF-2 Quinase/metabolismo , Fator 4 Ativador da Transcrição/biossíntese , Fator 4 Ativador da Transcrição/metabolismo , Sistemas CRISPR-Cas , Linhagem Celular , Citosol/enzimologia , Ativação Enzimática , Fator de Iniciação 2 em Eucariotos/metabolismo , Humanos , Masculino , Proteínas Mitocondriais/química , Chaperonas Moleculares/metabolismo , Fosforilação , Ligação Proteica
2.
Phys Chem Chem Phys ; 24(33): 19705-19715, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-35811566

RESUMO

Understanding the plasmonic coupling between a set of metallic nanoparticles (NPs) in a 2D array, and how a substrate affects such coupling, is fundamental for the development of optimized optoelectronic structures. Here, a simple semi-analytical procedure based on discrete dipole approximation (DDA) is reported to simulate the far-field and near-field properties of arrays of NPs, considering the coupling between particles, and the effect of the presence of a semiconductor substrate based on the image dipole approach. The method is validated for Ag NP dimers and single Ag NPs on a gallium nitride (GaN) substrate, a semiconductor widely used in optical devices, by comparison with the results obtained by the finite element method (FEM), indicating a good agreement in the weak coupling regime. Next, the method is applied to square and random arrays of Ag NPs on a GaN substrate. The increase in the surface density of NPs on a GaN substrate mainly results in a redshift of the dipolar resonance frequency and an increase in the near-field enhancement. This model, based on a single dipole approach, grants very low computational times, representing an advantage to predict the optical properties of large NP arrays on a semiconductor substrate for different applications.

3.
Mikrochim Acta ; 190(1): 40, 2022 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-36585475

RESUMO

Laser-induced graphene (LIG) is as a promising material for flexible microsupercapacitors (MSCs) due to its simple and cost-effective processing. However, LIG-MSC research and production has been centered on non-sustainable polymeric substrates, such as polyimide. In this work, it is presented a cost-effective, reproducible, and robust approach for the preparation of LIG structures via a one-step laser direct writing on chromatography paper. The developed strategy relies on soaking the paper in a 0.1 M sodium tetraborate solution (borax) prior to the laser processing. Borax acts as a fire-retardant agent, thus allowing the laser processing of sensitive substrates that other way would be easily destroyed under the high-energy beam. LIG on paper exhibiting low sheet resistance (30 Ω sq-1) and improved electrode/electrolyte interface was obtained by the proposed method. When used as microsupercapacitor electrodes, this laser-induced graphene resulted in specific capacitances of 4.6 mF cm-2 (0.015 mA cm-2). Furthermore, the devices exhibit excellent cycling stability (> 10,000 cycles at 0.5 mA cm-2) and good mechanical properties. By connecting the devices in series and parallel, it was also possible to control the voltage and energy delivered by the system. Thus, paper-based LIG-MSC can be used as energy storage devices for flexible, low-cost, and portable electronics. Additionally, due to their flexible design and architecture, they can be easily adapted to other circuits and applications with different power requirements.


Assuntos
Grafite , Capacitância Elétrica , Eletrodos , Lasers
4.
Eur Ann Allergy Clin Immunol ; 54(1): 25-29, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33354962

RESUMO

Summary: This study aimed to characterise how the follow-up of outpatients was done during the first months of COVID-19 pandemic by a multidisciplinary group of physicians involved in an asthma mHealth project. A cross-sectional study based on a web survey was conducted. The survey was sent to 123 physicians working at secondary care centres of Portugal and Spain, that participate in the INSPIRERS project. A total of 65 physicians completed the survey (53% response rate). They had a mean of 18 (11) years of clinical practice and 14% were residents. More than half were allergists (58%), 22% pulmonologists and 20% paediatricians. Most were working in Portugal (89%) and in public hospitals (88%). All were conducting consultations: 71% presential (median [p25 , p75] duration 30 [20, 30] min), 91% telephonic (15 [10, 20] min) and 20% video consultations (20 [10, 28] min). The median duration of presential consultations was significantly higher than pre-COVID-19 (20 [20, 30] min; p = 0.021). From the physicians conducting video consultations, 92% were allergists and only 54% considered that their institution provided adequate conditions. The physicians of the INSPIRERS group used telephonic consultations as the main alternative to presential ones and 1/5 used video consultations. These results suggest the need to rethink clinical follow-up services for outpatients in the near future increasing the use of telemedicine, especially video consultations.


Assuntos
COVID-19 , Médicos , Telemedicina , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Pandemias/prevenção & controle , Portugal , Encaminhamento e Consulta , SARS-CoV-2 , Inquéritos e Questionários
5.
Pharmacol Res ; 165: 105407, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33418029

RESUMO

Essential hypertension (HTN) is a disease where genetic and environmental factors interact to produce a high prevalent set of almost indistinguishable phenotypes. The weak definition of what is under the umbrella of HTN is a consequence of the lack of knowledge on the players involved in environment-gene interaction and their impact on blood pressure (BP) and mechanisms. The disclosure of these mechanisms that sense and (mal)adapt to toxic-environmental stimuli might at least determine some phenotypes of essential HTN and will have important therapeutic implications. In the present manuscript, we looked closer to the environmental sensor aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor involved in cardiovascular physiology, but better known by its involvement in biotransformation of xenobiotics through its canonical pathway. This review aims to disclose the contribution of the AHR-canonical pathway to HTN. For better mirror the complexity of the mechanisms involved in BP regulation, we privileged evidence from in vivo studies. Here we ascertained the level of available evidence and a comprehensive characterization of the AHR-related phenotype of HTN. We reviewed clinical and rodent studies on AHR-HTN genetic association and on AHR ligands and their impact on BP. We concluded that AHR is a druggable mechanistic linker of environmental exposure to HTN. We conclude that is worth to investigate the canonical pathway of AHR and the expression/polymorphisms of its related genes and/or other biomarkers (e.g. tryptophan-related ligands), in order to identify patients that may benefit from an AHR-centered antihypertensive treatment.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Humanos , Hipertensão/metabolismo , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos
6.
Eur J Neurol ; 28(1): 202-208, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32918842

RESUMO

BACKGROUND AND PURPOSE: Experimental studies suggest inflammation can contribute to blood barrier disruption and brain injury in cerebral venous thrombosis (CVT). We aimed to determine whether blood biomarkers of inflammation were associated with the evolution of brain lesions, persistent venous occlusion or functional outcome in patients with CVT. METHODS: Pathophysiology of Venous Infarction-Prediction of Infarction and Recanalization in CVT (PRIORITy-CVT) was a multicenter prospective cohort study of patients with newly diagnosed CVT. Evaluation of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) concentrations in peripheral blood samples was performed at admission in 62 patients. Additional quantification of interleukin (IL)-6 was performed at day 1, 3 and 8 in 35 patients and 22 healthy controls. Standardized magnetic resonance imaging was performed at day 1, 8 and 90. Primary outcomes were early evolution of brain lesion, early recanalization and functional outcome at 90 days. RESULTS: Interleukin-6 levels were increased in patients with CVT with a peak at baseline. IL-6, NLR and CRP levels were not related with brain lesion outcomes or early recanalization but had a significant association with unfavourable functional outcome at 90 days (IL-6: OR = 1.28, 95% CI: 1.05-1.56, P = 0.046; NLR: OR = 1.39, 95% CI: 1.4-1.87, P = 0.014; CRP: OR = 1.756, 95% CI: 1.010-3.051, P = 0.029). Baseline IL-6 had the best discriminative capacity, with an area under the receiver operating characteristic curve to predict unfavourable functional outcome of 0.74 (P = 0.031). CONCLUSIONS: Increased baseline levels of NLR, CRP and IL-6 may serve as new predictive markers of worse functional prognosis at 90 days in patients with CVT. No association was found between inflammatory markers and early evolution of brain lesion or venous recanalization.


Assuntos
Trombose Venosa , Biomarcadores , Humanos , Inflamação , Prognóstico , Estudos Prospectivos , Trombose Venosa/diagnóstico por imagem
7.
Br J Nutr ; 125(7): 768-779, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32807252

RESUMO

Protein supplementation may be beneficial for patients with chronic liver disease (CLD). This study compared the effects of whey protein isolate (WP) and casein (CA) supplementation on nutritional status and immune parameters of CLD patients who were randomly assigned to take 20 g of WP or CA twice per d as a supplement for 15 d. Body composition, muscle functionality and plasmatic immunomarkers were assessed before and after supplementation. Patients were also classified according to the model for end-stage liver disease (MELD) into less (MELD < 15) and more (MELD ≥ 15) severe disease groups. Malnutrition, determined by the Subjective Global Assessment at baseline, was observed in 57·4 % and 54·2 % of patients in the WP and CA groups, respectively (P = 0·649). Protein intake was lower at baseline in the WP group than in the CA group (P = 0·035), with no difference after supplementation (P = 0·410). Both the WP and CA MELD < 15 groups increased protein intake after supplementation according to the intragroup analysis. No differences were observed in body composition, muscle functionality, most plasma cytokines (TNF, IL-6, IL-1ß and interferon-γ), immunomodulatory proteins (sTNFR1, sTNFR2, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor) or immunomodulatory hormones (adiponectin, insulin and leptin) after supplementation in the WP groups at the two assessed moments. WP supplementation increased the levels of interferon-γ-induced protein-10/CXCL10 (P = 0·022), eotaxin-1/CCL11 (P = 0·031) and monocyte chemoattractant protein-1/CCL2 (P = 0·018) and decreased IL-5 (P = 0·027), including among those in the MELD ≥ 15 group, for whom IL-10 was also increased (P = 0·008). Thus, WP consumption by patients with CLD impacted the immunomodulatory responses when compared with CA with no impact on nutritional status.

8.
Adv Exp Med Biol ; 1306: 109-120, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959909

RESUMO

Our general goal was to non-invasively evaluate kidney tubular dysfunction. We developed a strategy based on cysteine (Cys) disulfide stress mechanism that underlies kidney dysfunction. There is scarce information regarding the fate of Cys-disulfides (CysSSX), but evidence shows they might be detoxified in proximal tubular cells by the action of N-acetyltransferase 8 (NAT8). This enzyme promotes the addition of an N-acetyl moiety to cysteine-S-conjugates, forming mercapturates that are eliminated in urine. Therefore, we developed a strategy to quantify mercapturates of CysSSX in urine as surrogate of disulfide stress and NAT8 activity in kidney tubular cells. We use a reduction agent for the selective reduction of disulfide bonds. The obtained N-acetylcysteine moiety of the mercapturates from cysteine disulfides was monitored by fluorescence detection. The method was applied to urine from mice and rat as well as individuals with healthy kidney and kidney disease.


Assuntos
Cisteína , Nefropatias , Acetilcisteína , Animais , Dissulfetos , Rim , Camundongos , Ratos
9.
Pharmacol Res ; 159: 104869, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32416216

RESUMO

BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) is associated to a high prevalence of resistant arterial hypertension (HTN) justifying the research on novel targets. Chronic intermittent hypoxia (CIH) is a key feature in the development of OSA comorbidities, including HTN. EXPERIMENTAL APPROACH: We used a rat model of CIH-induced HTN to disclose the hypothesis that the aryl hydrocarbon receptor (AHR) is activated by CIH once it shares the same binding partner of HIF-1α and promotes pro-oxidant, pro-inflammatory (NF-kB) and pro-fibrotic events in common with CIH. KEY RESULTS: Upon established hypertension (21 days exposure to CIH), we observed an increase in Cyp1a1 mRNA in kidney cortex (6-fold), kidney medulla (3-fold) and liver (3-fold), but not in other tissues. Increased renal expression of Ahr and markers of inflammation (Rela), epithelial to mesenchymal transition markers, the rate-controlling step of gluconeogenesis, Pepck1, and members of HIF-pathway, namely, Hif3a were also observed. Daily administration (14 days) of AHR antagonist, CH-223191 (5 mg.kg-1.day-1, gavage), simultaneously to CIH prevented the increase in systolic blood pressure (SBP) by 53 ± 12% and in diastolic blood pressure (DBP) by 44 ± 16%. Moreover, its administration (14 days) upon already established HTN reversed the increase in SBP by 52 ± 12%. CONCLUSION AND IMPLICATIONS: CIH caused an activation of AHR signaling particularly in the kidney and its pharmacological blockade had a significant impact reverting already established HTN. This first evidence inspires innovative research opportunities for the understanding and treatment of this particular type of HTN.


Assuntos
Anti-Hipertensivos/farmacologia , Compostos Azo/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipóxia/complicações , Rim/efeitos dos fármacos , Pirazóis/farmacologia , Receptores de Hidrocarboneto Arílico/antagonistas & inibidores , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Doença Crônica , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibrose , Hipertensão/etiologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Ratos Wistar , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Transdução de Sinais , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
10.
Int Arch Occup Environ Health ; 93(4): 491-502, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31832764

RESUMO

INTRODUCTION: Experiments in animals exposed to mercury (Hg) in different chemical states have shown thyroid parenchymal and hormone alterations. However, these experiments did not allow the establishment of dose-response curves or provide an understanding of whether these Hg effects on the thyroid parenchyma occur in humans. OBJECTIVE: To evaluate the association between chronic occupational exposure to metallic Hg and alterations in thyroid hormones and gland parenchyma 14 years after the last exposure. METHODS: A cross-sectional study including 55 males exposed in the past to metallic Hg and 55 non-exposed males, paired by age, was conducted in the Hospital das Clínicas (Brazil) from 2016 to 2017. Serum concentrations of total and free triiodothyronine (TT3 and FT3), free thyroxine (FT4), thyrotropin (TSH), reverse T3 (RT3), selenium and antithyroid antibody titers were obtained. The Hg and iodine concentrations were measured in urine. The thyroid parenchyma was evaluated by B-mode ultrasonography with Doppler. The nodules with aspects suspicious for malignancy were submitted to aspiration puncture with a thin needle, and the cytology assessment was classified by the Bethesda system. The t test or Mann-Whitney test, Chi-square test and Spearman correlation were used to compare the exposed and non-exposed groups and examine the relationships between the variables. Univariate and multivariate logistic regression models were used to trace determinants of the risk of thyroid hormone alteration. Statistical significance was defined by p < 0.05. RESULTS: The urinary Hg average was significantly higher in the exposed group than in the non-exposed group (p < 0.01). The mean TSH serum concentration in the exposed group was higher, with a statistically significant difference between the groups (p = 0.03). Serum concentrations of TSH exceeded the normality limit (4.20 µIU/ml) in 13 exposed individuals (27.3%) and 4 non-exposed individuals (7.3%), with a statistically significant association between the hormonal increase and exposure to Hg (p = 0.02). In the logistic regression model, exposure to Hg (yes or no) showed an odds ratio = 4.86 associated with an increase of TSH above the normal limit (p = 0.04). The serum concentrations of RT3 showed a statistically borderline difference between the groups (p = 0.06). There was no statistically significant difference between the mean TT3, FT3 and FT4 serum concentrations in the Hg-exposed group compared to the non-exposed group. The proportions of the echogenicity alterations were higher in the exposed group compared to the non-exposed group (27.3% versus 9.1%; p = 0.03). Papillary carcinomas were documented in three exposed individuals and one non-exposed individual. A follicular carcinoma was recorded in one non-exposed individual. CONCLUSIONS: Due to the higher serum TSH concentration and the prevalence of parenchymal alterations in the Hg-exposed group, even after cessation of exposure, it is recommended that the thyroid status of exposed workers be followed for a long period.


Assuntos
Mercúrio/toxicidade , Exposição Ocupacional/efeitos adversos , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/sangue , Neoplasias da Glândula Tireoide/epidemiologia , Adulto , Idoso , Brasil , Carcinoma Papilar/epidemiologia , Estudos Transversais , Humanos , Iodo/urina , Masculino , Mercúrio/urina , Pessoa de Meia-Idade , Selênio/sangue , Glândula Tireoide/diagnóstico por imagem , Ultrassonografia Doppler
11.
J Eur Acad Dermatol Venereol ; 33(11): 2019-2028, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31713914

RESUMO

BACKGROUND: The first International Society of Atopic Dermatitis (ISAD) global meeting dedicated to atopic dermatitis (AD) in Sub-Saharan Africa (SSA) was held in Geneva, Switzerland in April 2019. A total of 30 participants were present at the meeting, including those from 17 SSA countries, representatives of the World Health Organization (WHO), the International Foundation for Dermatology (IFD) (a committee of the International League of Dermatological Societies, ILDS www.ilds.org), the Fondation pour la Dermatite Atopique, as well as specialists in telemedicine, artificial intelligence and therapeutic patient education (TPE). RESULTS: AD is one of the most prevalent chronic inflammatory skin diseases in SSA. Besides neglected tropical diseases (NTDs) with a dermatological presentation, AD requires closer attention from the WHO and national Departments of Health. CONCLUSIONS: A roadmap has been defined with top priorities such as access to essential medicines and devices for AD care, in particular emollients, better education of primary healthcare workers for adequate triage (e.g. better educational materials for skin diseases in pigmented skin generally and AD in particular, especially targeted to Africa), involvement of traditional healers and to a certain extent also patient education, bearing in mind the barriers to effective healthcare faced in SSA countries such as travel distances to health facilities, limited resources and the lack of dermatological expertise. In addition, several initiatives concerning AD research in SSA were discussed and should be implemented in close collaboration with the WHO and assessed at follow-up meetings, in particular, at the next ISAD meeting in Seoul, South Korea and African Society of Dermatology and Venereology (ASDV) meeting in Nairobi, Kenya, both in 2020.


Assuntos
Dermatite Atópica , África Subsaariana/epidemiologia , Congressos como Assunto , Dermatite Atópica/diagnóstico , Dermatite Atópica/epidemiologia , Dermatite Atópica/terapia , Humanos
12.
J Hum Nutr Diet ; 32(6): 693-701, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31334582

RESUMO

BACKGROUND: Weight gain and obesity are important issues in liver transplant (LTx) recipients. Although dietary habits are probably related to excessive weight gain after LTx, some studies have failed to demonstrate these associations. The present study aimed to assess eating behaviour and verify its association with weight gain and excessive weight among LTx recipients. METHODS: The investigation comprised a cross-sectional study. Post-LTx patients, aged >18 years were evaluated about their eating behaviour [Three Factor Eating Questionnaire-R21 (TFEQ-R21)]. The scores of the TFEQ-R21 [uncontrolled eating (UE), cognitive restraint (CR) and emotional eating (EE)] were determined. Excessive weight was classified as body mass index ≥25 kg/m² and obesity ≥30 kg/m². RESULTS: In total, 270 patients (age 58.0 years; range 20.0-77.0 years; 64.1% men) were assessed. Average weight gain was 8.0 kg (range -16.0 to 41.0 kg). Of the patients, 64.1% (n = 173) had excessive weight and 23.3% (n = 63) were obese. Post-LTx weight gain was significantly correlated with UE (r = 0.311, P < 0.001) and EE (r = 0.287, P < 0.001). Patients with excessive weight had significantly higher scores than others: CR (61.0; range 0-122.0 versus 44.0; range 0-116.0) (P = 0.003) and EE (11.0; range 0-100.0 versus 0.0; range 0-100.0) (P = 0.030). Patients with obesity had higher scores than non-obese UE (22.0; range 0-77.0 versus 14.0; range 0-85.0; P = 0.028), CR (55.0; range 11.0-116.0 versus 50.0; range 0-122.0) (P = 0.017) and EE (16.0; range 0-100.0 versus 5.0; range 0-100.0) individuals (P < 0.001). The greatest quartiles of weight gain had higher scores on the eating behaviours of UE and EE, especially those with weight gain ≥14 kg. UE was associated with weight gain. CR was associated with being overweight. EE was associated with obesity. CONCLUSIONS: Uncontrolled eating is associated with weight gain, CR was associated with excessive weight and EE was associated with obesity after LTx.


Assuntos
Comportamento Alimentar/psicologia , Transplante de Fígado/psicologia , Obesidade/psicologia , Autocontrole/psicologia , Aumento de Peso , Adulto , Idoso , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Sobrepeso/psicologia
13.
Allergol Immunopathol (Madr) ; 47(2): 133-140, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30482599

RESUMO

INTRODUCTION: Cow's milk protein allergy (CMPA) is the most common food allergy in children worldwide. Some children have severe and persistent CMPA, with near-fatal reactions after exposure to trace amounts of cow's milk-proteins (CMP). Strict avoidance diet is difficult, negatively affects quality of life and represents a conservative approach. Therefore, different therapeutic strategies are necessary. OBJECTIVE: We aimed to assess long-term efficacy and safety of oral immunotherapy (OIT) in children with severe and long-lasting IgE-mediated CMPA. MATERIALS AND METHODS: The authors present four case reports of patients with CMPA who underwent CMP-OIT, that have been under long-term follow-up up to nine years. We provide information about the clinical and laboratory evaluation. Skin prick tests (SPT), specific IgE and IgG4 were performed before, during, and after OIT. Immune profile after OIT was assessed by flow cytometry (lymphocyte subsets, regulatory T and B cells). RESULTS: The success rate was 100%, and all patients currently have a free diet with minimal diary ingestion of 200mL CMP or equivalent. Specific IgE levels and SPT to CMP have progressively decreased, and specific IgG4 levels have increased. CD4+CD25+CD127-/dim regulatory T cells were increased after OIT. CONCLUSIONS: OIT ensured a clinical tolerance state after up to nine years, confirmed by both clinical and immune profile, allowing a diet without restrictions, with high satisfaction from patients and caregivers. We emphasize that OIT should be performed only by allergy experts in the hospital setting, and that only motivated families should be enrolled, since it is essential to ensure CMP daily intake at home.


Assuntos
Alérgenos/uso terapêutico , Dessensibilização Imunológica/métodos , Hipersensibilidade a Leite/terapia , Linfócitos T Reguladores/imunologia , Administração Oral , Adolescente , Adulto , Alérgenos/imunologia , Animais , Bovinos , Criança , Feminino , Seguimentos , Humanos , Tolerância Imunológica , Imunoglobulina E/metabolismo , Masculino , Hipersensibilidade a Leite/imunologia , Proteínas do Leite/imunologia , Adulto Jovem
14.
Allergol Immunopathol (Madr) ; 47(2): 128-132, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30249451

RESUMO

INTRODUCTION: Beta-lactams are the most frequently used antibiotics in pediatric age. Anaphylactic reactions may occur and need to be properly studied, but studies in children are scarce. OBJECTIVE: Characterization of case reports of anaphylaxis in children referred to an allergy department with suspected beta-lactams hypersensitivity. MATERIALS AND METHODS: Retrospective analysis of all children referred to our Drug Allergy Center with suspected beta-lactams hypersensitivity between January 2011 and December 2016. Description of the drug allergy work-up performed studied according to standardized diagnostic procedures of ENDA/EAACI, including specific-IgE assay, skin prick and intradermal tests and diagnostic/alternative drug challenge tests. RESULTS: 146 children with suspected beta-lactams hypersensitivity were studied, and in 21 (14.4%) the diagnosis was confirmed. In all of them, except for three children, an alternative beta-lactam was found. In seven children (33.3% of those with confirmed beta-lactams hypersensitivity) anaphylaxis was confirmed, and all of them described reactions with cutaneous and respiratory or gastrointestinal involvement. The culprit drug was amoxicillin in six and flucloxacillin in one. In this sample, we also performed oral challenge with cefuroxime, being negative in all cases. Almost all cases of confirmed anaphylaxis (six from seven cases) were IgE mediated, with positive skin tests despite negative serum specific-IgE. CONCLUSIONS: Allergic reactions to beta-lactams, although rare in children, require a detailed clinical history and a specialized drug allergy work-up to allow a correct diagnosis as well as to avoid the possibility of a potential life-threatening reaction and provide alternative drugs.


Assuntos
Alérgenos/imunologia , Anafilaxia/diagnóstico , Hipersensibilidade a Drogas/diagnóstico , Pele/patologia , beta-Lactamas/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Masculino , Estudos Retrospectivos , Testes Cutâneos , Inquéritos e Questionários
16.
Biochim Biophys Acta Gen Subj ; 1862(3): 427-439, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29126854

RESUMO

BACKGROUND: Quantum dots (QDs) are outstanding nanomaterials of great interest to life sciences. Their conjugation versatility added to unique optical properties, highlight these nanocrystals as very promising fluorescent probes. Among uncountable new nanosystems, in the last years, QDs conjugated to glycans or lectins have aroused a growing attention and their application as a tool to study biological and functional properties has increased. SCOPE OF REVIEW: This review describes the strategies, reported in the literature, to conjugate QDs to lectins or carbohydrates, providing valuable information for the elaboration, improvement, and application of these nanoconjugates. It also presents the main applications of these nanosystems in glycobiology, such as their potential to study microorganisms, the development of diseases such as cancer, as well as to develop biosensors. MAJOR CONCLUSIONS: The development of glyconanoparticles based on QDs emerged in the last decade. Many works reporting the conjugation of QDs with carbohydrates and lectins have been published, using different strategies and reagents. These bioconjugates enabled studies that are very sensitive and specific, with potential to detect and elucidate the glycocode expressed in various normal or pathologic conditions. GENERAL SIGNIFICANCE: Produce a quick reference source over the main advances reached in the glyconanotechnology using QDs as fluorescent probes.


Assuntos
Glicoconjugados , Nanotecnologia/métodos , Pontos Quânticos , Técnicas Bacteriológicas , Técnicas Biossensoriais , Metabolismo dos Carboidratos , Carboidratos/análise , Linhagem Celular Tumoral , Técnicas de Química Analítica/métodos , Fluorescência , Glicoconjugados/administração & dosagem , Glicoconjugados/química , Glicoconjugados/uso terapêutico , Humanos , Lectinas/administração & dosagem , Lectinas/química , Nanopartículas Metálicas , Modelos Moleculares , Micologia/métodos , Nanotecnologia/tendências , Neoplasias/química , Neoplasias/diagnóstico , Imagem Óptica/métodos , Parasitologia/métodos , Pontos Quânticos/administração & dosagem , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico
17.
J Appl Microbiol ; 125(5): 1238-1252, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30053345

RESUMO

The resistance of micro-organisms to antimicrobial agents has been a challenge to treat animal and human infections, and for environmental control. Lectins are natural proteins and some are potent antimicrobials through binding to carbohydrates on microbial surfaces. Oligomerization state of lectins can influence their biological activity and maximum binding capacity; the association among lectin polypeptide chains can alter the carbohydrate-lectin binding dissociation rate constants. Antimicrobial mechanisms of lectins include the pore formation ability, followed by changes in the cell permeability and latter, indicates interactions with the bacterial cell wall components. In addition, the antifungal activity of lectins is associated with the chitin-binding property, resulting in the disintegration of the cell wall or the arrest of de novo synthesis from the cell wall during fungal development or division. Quorum sensing is a cell-to-cell communication process that allows interspecies and interkingdom signalling which coordinate virulence genes; antiquorum-sensing therapies are described for animal and plant lectins. This review article, among other approaches, evaluates lectins as antimicrobials.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Resistência Microbiana a Medicamentos , Fungos/efeitos dos fármacos , Lectinas/farmacologia , Animais , Infecções Bacterianas/microbiologia , Humanos , Micoses/microbiologia , Percepção de Quorum/efeitos dos fármacos
18.
Arch Womens Ment Health ; 21(4): 453-459, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29502281

RESUMO

We have defined a psychological intervention based on cognitive narrative therapy and the Ottawa decision framework to reduce adjustment problems following a termination of pregnancy (TOP) after a positive prenatal diagnosis (PND). The intervention is composed of four sessions: decision, subjectivation, metaphorization, and projecting. This study aims to assess the effectiveness of a cognitive narrative intervention to prevent depression and anxiety symptoms after TOP. The intervention was accepted by 24 participants. The outcome is compared with a control group of 67 women who also terminated a pregnancy after PND. Participants were from several Portuguese institutions; 64.4% had a genetic and 35.6% had ultrasound diagnosis; the mean age was 30.0 years and the mean gestational age was 19 weeks. There are two evaluations: a baseline at the 15th day and a sixth month follow-up after TOP, using Beck Depression Inventory, Zung Anxiety Scale, Perinatal Grief Scale, and an instrument capturing participant satisfaction. Six months after TOP, there is a lower mean of anxiety and depression (p < 0.05), between groups, with effect sizes on the follow-up of 0.54 for depression, 0.41 for anxiety, and 0.23 for perinatal grief. This intervention has very positive effects on women mental health, and we emphasize the importance of the meaning-making process in the context of terminating a wanted pregnancy.


Assuntos
Aborto Eugênico/psicologia , Ansiedade/prevenção & controle , Terapia Cognitivo-Comportamental/métodos , Depressão/prevenção & controle , Terapia Narrativa/métodos , Diagnóstico Pré-Natal/psicologia , Adulto , Feminino , Pesar , Humanos , Estudos Longitudinais , Portugal , Gravidez , Resultado do Tratamento
19.
Lett Appl Microbiol ; 67(1): 54-63, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29603295

RESUMO

Zymomonas mobilis has long attracted attention owing to its capacity to ferment hexose to ethanol. From a taxonomic viewpoint, Z. mobilis is a unique species of the genus Zymomonas, separated into three subspecies, Z. mobilis subsp. mobilis, Z. mobilis subsp. pomaceae and Z. mobilis subsp. francensis on the basis of physiological tests, which are often unreliable owing to the genetic proximity among these species. Currently, the use of molecular techniques is more appropriate for identification of these bacterial subspecies. In this study, the 32 strains of Z. mobilis present in the UFPEDA bacterial collection were characterized using molecular techniques, such as sequencing of the 16S rDNA gene and its theoretical restriction profile, classifying them as members of the subspecies, Z. mobilis subsp. mobilis. In addition, anaerobic cultivations were performed, which showed the biological diversity of the strains in terms of growth, sugar consumption and ethanol production. From these results, it was possible to identify the strain Z-2-80 as a promising bacterium for use in the fermentation process. SIGNIFICANCE AND IMPACT OF THE STUDY: Zymomonas mobilis is a bacterium of great relevance to biotechnology, owing to its capacity to ferment hexose to ethanol. On a molecular basis, 32 isolates were identified as Z. mobilis subsp. mobilis. However, intraspecific diversity was identified when these were grown under strictly anaerobic conditions. The results obtained from this study suggest a strain of Z. mobilis as an alternative for use in the fermentation process.


Assuntos
Reatores Biológicos/microbiologia , DNA Bacteriano/genética , Etanol/metabolismo , Zymomonas/classificação , Zymomonas/metabolismo , Anaerobiose , Brasil , DNA Ribossômico/genética , Fermentação , Hexoses/metabolismo , RNA Ribossômico 16S/genética , Zymomonas/genética , Zymomonas/isolamento & purificação
20.
Adv Exp Med Biol ; 1071: 83-88, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30357737

RESUMO

Previous data showed the lack of efficacy of an adrenoceptor antagonist to revert hypertension induced by chronic intermittent hypoxia (CIH). We hypothesized that, in addition to sympathetic activation, CIH may change the availability and dynamics of cysteine. Temporal variation in total cysteine and its fractions, free reduced, free oxidized and protein-bound (CysSSP), were measured in homogenates of kidney cortex and medulla of Wistar rats. Animals were exposed to CIH for 14, 21 and 60 days and cysteine fractions and fibronectin gene expression were assessed at these time-points. Two different phases in cysteine dynamics were identified. An early phase (14d) characterized by an increase in cysteine oxidation and CysSSP forms. Late events (>21d) were characterized by a global reduction in cysteine, minimum level of CysSSP and maximum overexpression of fibronectin in kidney cortex. In conclusion, cysteine dynamics is influenced by the duration of CIH exposure: first there is a cysteine disulfide stress-like adaptive response followed by a progressive loss of cysteine availability and a decrease in CysSSP fraction. Kidney fibrosis associated to an unbalance in cysteine dynamics might contribute to the inefficacy of available antihypertensive drugs in patients with delayed diagnosis of sleep apnea.


Assuntos
Cisteína , Hipertensão/fisiopatologia , Hipóxia/fisiopatologia , Estresse Oxidativo , Animais , Ratos , Ratos Wistar
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