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3.
Curr Opin Allergy Clin Immunol ; 20(4): 333-337, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32398420

RESUMO

PURPOSE OF REVIEW: Omalizumab has been proposed for controlling adverse reactions during drug desensitization. Our aim is to know the current evidence involving the use of omalizumab in drug-allergy desensitization. RECENT FINDINGS: Drug-allergy desensitization is not risk free, but it is a useful procedure and has been applied for drug hypersensitivity reactions with mast cells degranulation through IgE and non-IgE mechanisms. Since 2007, omalizumab has been considered as a potential strategy to prevent adverse reactions.Our review found few case reports and only one randomized double-blind, placebo-controlled study, using different omalizumab regimens prior to drug desensitization. This scarce evidence is insufficient to predict the effectiveness of omalizumab in rapid drug desensitization procedures, but it may be useful in future studies of omalizumab or related next-generation antibodies. SUMMARY: Omalizumab or other IgE-targeting biologics, either a fixed dose of 300 mg omalizumab or a dose-related total IgE level and body mass weight may be an option for patients with IgE-mediated or mast cell drug reactions in troublesome desensitization.

4.
Biomarkers ; 25(2): 201-211, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32063068

RESUMO

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome for which clear evidence of effective therapies is lacking. Understanding which factors determine this heterogeneity may be helped by better phenotyping. An unsupervised statistical approach applied to a large set of biomarkers may identify distinct HFpEF phenotypes.Methods: Relevant proteomic biomarkers were analyzed in 392 HFpEF patients included in Metabolic Road to Diastolic HF (MEDIA-DHF). We performed an unsupervised cluster analysis to define distinct phenotypes. Cluster characteristics were explored with logistic regression. The association between clusters and 1-year cardiovascular (CV) death and/or CV hospitalization was studied using Cox regression.Results: Based on 415 biomarkers, we identified 2 distinct clusters. Clinical variables associated with cluster 2 were diabetes, impaired renal function, loop diuretics and/or betablockers. In addition, 17 biomarkers were higher expressed in cluster 2 vs. 1. Patients in cluster 2 vs. those in 1 experienced higher rates of CV death/CV hospitalization (adj. HR 1.93, 95% CI 1.12-3.32, p = 0.017). Complex-network analyses linked these biomarkers to immune system activation, signal transduction cascades, cell interactions and metabolism.Conclusion: Unsupervised machine-learning algorithms applied to a wide range of biomarkers identified 2 HFpEF clusters with different CV phenotypes and outcomes. The identified pathways may provide a basis for future research.Clinical significanceMore insight is obtained in the mechanisms related to poor outcome in HFpEF patients since it was demonstrated that biomarkers associated with the high-risk cluster were related to the immune system, signal transduction cascades, cell interactions and metabolismBiomarkers (and pathways) identified in this study may help select high-risk HFpEF patients which could be helpful for the inclusion/exclusion of patients in future trials.Our findings may be the basis of investigating therapies specifically targeting these pathways and the potential use of corresponding markers potentially identifying patients with distinct mechanistic bioprofiles most likely to respond to the selected mechanistically targeted therapies.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Fenótipo , Idoso , Biomarcadores/análise , Análise por Conglomerados , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Proteômica , Volume Sistólico
5.
Dig Dis ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32015237

RESUMO

BACKGROUND: Refractory Celiac Disease type II (RCD-II) is a very rare yet severe complication of Celiac Disease (CD) with a 50% rate of progression to EATL (Enteropathy-associated T-cell lymphoma). Timely diagnosis and treatment of RCD-II is of the essence and requires the identification of a population of frequently clonal, phenotypically aberrant intraepithelial lymphocytes (IELs). Flow Cytometry (FCM) of intestinal IELs is the recommended method to identify the aberrant sCD3- icCD3ε+ IELs, and a proportion of >20% is diagnostic of RCD-II. There is substantial heterogeneity in the clinical course of RCD-II, and insufficient information on prognostic factors. AIM: To stablish flow cytometric predictors of the clinical evolution of RCD-II, to help guide treatment approaches. PATIENTS AND METHODS: Retrospective single center study of clinical and immunological features of 6 RCD-II patients and a control group, both identified from a 2000-patient cohort over 16 years. IEL subset frequencies and the intensity of staining for surface (s) and intracytoplasmic (ic) CD3ε+ on IEL subsets were quantified and correlated with the clinical outcome. RESULTS: Unexpectedly, the frequency of aberrant sCD3- icCD3ε+ cells at diagnosis did not correlate with histological or clinical affection. However, a higher intensity of icCD3ε+ staining in the aberrant IELs relative to expression on normal IELs correlated with monoclonality and with worse clinical outcomes. CONCLUSION: The ratio of icCD3ε+ on aberrant IELs vs normal IELs appears to be a useful indicator of prognosis at the time of diagnosis, and may represent a novel tool in the follow-up of RCD-II patients after therapy.

6.
mBio ; 11(1)2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911495

RESUMO

Caspase recruitment domain-containing protein 9 (CARD9) is a critical adaptor molecule triggered by the interaction of C-type lectin receptors (CLRs) with carbohydrate motifs found in fungi. Consequently, clinical and animal studies indicate that CARD9 is an important regulator of protective immunity against fungal pathogens. Previous studies suggest that CARD9 is important for the induction of protection against Cryptococcus neoformans, an opportunistic fungal pathogen that causes life-threatening infections of the central nervous system in immunocompromised patients. However, the effect of CARD9 deficiency on the induction of protective immune responses against C. neoformans is unknown. Immunization with a C. neoformans mutant that overexpresses the transcription factor zinc finger 2, denoted LW10, results in protection against an otherwise lethal challenge with wild-type (WT) C. neoformans Our results showed that CARD9 is essential for the induction of vaccine-mediated immunity against C. neoformans infection. We observed significant decreases in interleukin-17 (IL-17) production and significant increases in Th2-type cytokine (IL-4, IL-5, and IL-13) production in CARD9-deficient mice after inoculation with strain LW10. While leukocyte infiltration to the lungs of CARD9-deficient mice was similar in LW10 and WT C. neoformans-infected mice, macrophages derived from CARD9-deficient mice inherently skewed toward an M2 activation phenotype, were unable to contain the growth of LW10, and failed to produce nitric oxide in response to infection with LW10 or stimulation with lipopolysaccharide. These results suggest that CARD9-mediated signaling is required for M1 macrophage activation and fungicidal activity necessary for the induction of vaccine-mediated immunity against C. neoformans IMPORTANCE Cryptococcus neoformans is a fungal pathogen that is found throughout the environment and can cause life-threatening infections of the lung and central nervous system in severely immunocompromised individuals. Caspase recruitment domain-containing protein 9 (CARD9) is a critical molecule that is activated after interactions of C-type lectin receptors (CLRs) found on the surfaces of specific immune cells, with carbohydrate structures associated with fungi. Patients with defects in CARD9 are significantly more susceptible to a multitude of fungal infections. C. neoformans contains several carbohydrate structures that interact with CLRs on immune cells and activate CARD9. Consequently, these studies evaluated the necessity of CARD9 for the induction of protective immunity against C. neoformans infection. These results are important, as they advance our understanding of cryptococcal pathogenesis and host factors necessary for the induction of protective immunity against C. neoformans.

8.
J Allergy Clin Immunol Pract ; 8(3): 1022-1031.e1, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31785410

RESUMO

BACKGROUND: Diagnosis of hypersensitivity (HS) reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in children is complex. The real prevalence of NSAID HS remains unknown because a drug provocation test (DPT) is not always performed with the culprit NSAID. OBJECTIVE: To describe and compare the diagnostic workup among different European centers and to find out the real proportion of NSAID HS by performing a DPT with the culprit drug. METHODS: We retrospectively collected data from children (0-10 years) and adolescents (10-18 years) with a history of NSAID reactions and who underwent a complete allergy workup including DPTs with the culprit in 6 different pediatric centers: Belgrade, Florence, Geneva, Madrid, Porto, and Rome. RESULTS: A total of 693 children with a history of NSAID reactions were enrolled, and a total of 526 DPTs were performed with the culprit NSAID. The diagnosis of NSAID HS was confirmed in 19.6% (103 of 526) of children by performing a DPT with the culprit drug. The major differences in the allergy workup among the 6 centers concerned the duration of the DPT and the practical use of skin tests for diagnosing NSAID HS. In addition, the use of acetyl salicylic acid to differentiate single reactor or cross-intolerance patients is not common, except in Spain. CONCLUSION: The value of this study is that although different approaches are used around Europe to diagnose NSAID HS, we found that the percentage of confirmed NSAID HS is less than 20%. This highlights the importance of the DPT in confirming or excluding NSAID HS in the pediatric population.

9.
Rev. psicol. deport ; 29(1): 133-142, 2020. tab, graf
Artigo em Espanhol | IBECS-Express | ID: ibc-FGT-3936

RESUMO

El estudio propone un modelo de patrocinio deportivo que toma como eje la transferencia entre evento y marca en términos de valor y experiencia, abundando en sus antecedentes y efectos. Encuestando en 2012 a 364 asistentes al GP de Fórmula 1 de València se concluye que no se transfiere el valor del evento a la marca, pero sí la experiencia. Asimismo, se observa que ambos términos (experiencia y valor) están significativamente relacionados. Adicionalmente, se confirma que motivación, identificación e implicación son antecedentes del eje del modelo, junto con todos los efectos propuestos


This study proposes a general model for sports sponsorship which takes as its central concept the transfer between event and brand in terms of value and experience, elaborating on antecedent and effects. 364 questionnaires from Valencia GP Formula 1 2012 fans revealed that value is not transferred from event to brand, whereas, the experience is transferred. The observation is also made that the two terms (experience and perceived value) are significantly related. Additionally, the study confirms that are the antecedent variables of the central concept of the model, together with the proposed effects


O estudo propõe um modelo de patrocínio esportivo que se concentra na transferência entre evento e marca em termos de valor e experiência, abundando em seus antecedentes e efeitos. Em 2012, 364 participantes do GP de Fórmula 1 de Valência concluíram que o valor do evento não é transferido para a marca, mas a experiência é. Observa-se também que ambos os termos (experiência e valor) estão significativamente relacionados. Além disso, confirma-se que motivação, identificação e envolvimento são antecedentes do eixo do modelo, juntamente com todos os efeitos propostos

10.
mBio ; 10(6)2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31744923

RESUMO

Arrestins, a structurally specialized and functionally diverse group of proteins, are central regulators of adaptive cellular responses in eukaryotes. Previous studies on fungal arrestins have demonstrated their capacity to modulate diverse cellular processes through their adaptor functions, facilitating the localization and function of other proteins. However, the mechanisms by which arrestin-regulated processes are involved in fungal virulence remain unexplored. We have identified a small family of four arrestins, Ali1, Ali2, Ali3, and Ali4, in the human fungal pathogen Cryptococcus neoformans Using complementary microscopy, proteomic, and reverse genetics techniques, we have defined a role for Ali1 as a novel contributor to cytokinesis, a fundamental cell cycle-associated process. We observed that Ali1 strongly interacts with proteins involved in lipid synthesis, and that ali1Δ mutant phenotypes are rescued by supplementation with lipid precursors that are used to build cellular membranes. From these data, we hypothesize that Ali1 contributes to cytokinesis by serving as an adaptor protein, facilitating the localization of enzymes that modify the plasma membrane during cell division, specifically the fatty acid synthases Fas1 and Fas2. Finally, we assessed the contributions of the C. neoformans arrestin family to virulence to better understand the mechanisms by which arrestin-regulated adaptive cellular responses influence fungal infection. We observed that the C. neoformans arrestin family contributes to virulence, and that the individual arrestin proteins likely fulfill distinct functions that are important for disease progression.IMPORTANCE To survive under unpredictable conditions, all organisms must adapt to stressors by regulating adaptive cellular responses. Arrestin proteins are conserved regulators of adaptive cellular responses in eukaryotes. Studies that have been limited to mammals and model fungi have demonstrated that the disruption of arrestin-regulated pathways is detrimental for viability. The human fungal pathogen Cryptococcus neoformans causes more than 180,000 infection-related deaths annually, especially among immunocompromised patients. In addition to being genetically tractable, C. neoformans has a small arrestin family of four members, lending itself to a comprehensive characterization of its arrestin family. This study serves as a functional analysis of arrestins in a pathogen, particularly in the context of fungal fitness and virulence. We investigate the functions of one arrestin protein, Ali1, and define its novel contributions to cytokinesis. We additionally explore the virulence contributions of the C. neoformans arrestin family and find that they contribute to disease establishment and progression.


Assuntos
Arrestina/metabolismo , Ciclo Celular , Suscetibilidade a Doenças , Fungos/fisiologia , Micoses/microbiologia , Arrestina/genética , Biomarcadores , Ciclo Celular/genética , Citocinese , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Metabolismo dos Lipídeos , Modelos Biológicos , Mutação , Micoses/metabolismo , Virulência , Proteínas ras/metabolismo
11.
Sci Rep ; 9(1): 17810, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31780737

RESUMO

In chronic kidney disease (CKD), hyperphosphatemia-induced inflammation aggravates vascular calcification (VC) by increasing vascular smooth muscle cell (VSMC) osteogenic differentiation, ADAM17-induced renal and vascular injury, and TNFα-induction of neutral-sphingomyelinase2 (nSMase2) to release pro-calcifying exosomes. This study examined anti-inflammatory ß-glucans efficacy at attenuating systemic inflammation in health, and renal and vascular injury favoring VC in hyperphosphatemic CKD. In healthy adults, dietary barley ß-glucans (Bßglucans) reduced leukocyte superoxide production, inflammatory ADAM17, TNFα, nSMase2, and pro-aging/pro-inflammatory STING (Stimulator of interferon genes) gene expression without decreasing circulating inflammatory cytokines, except for γ-interferon. In hyperphosphatemic rat CKD, dietary Bßglucans reduced renal and aortic ADAM17-driven inflammation attenuating CKD-progression (higher GFR and lower serum creatinine, proteinuria, kidney inflammatory infiltration and nSMase2), and TNFα-driven increases in aortic nSMase2 and calcium deposition without improving mineral homeostasis. In VSMC, Bßglucans prevented LPS- or uremic serum-induced rapid increases in ADAM17, TNFα and nSMase2, and reduced the 13-fold higher calcium deposition induced by prolonged calcifying conditions by inhibiting osteogenic differentiation and increases in nSMase2 through Dectin1-independent actions involving Bßglucans internalization. Thus, dietary Bßglucans inhibit leukocyte superoxide production and leukocyte, renal and aortic ADAM17- and nSMase2 gene expression attenuating systemic inflammation in health, and renal injury and aortic calcification despite hyperphosphatemia in CKD.

12.
Biol Sex Differ ; 10(1): 44, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477151

RESUMO

BACKGROUND: Cryptococcus neoformans, the causative agent of cryptococcosis, causes ~ 181,000 deaths annually, with males having a higher incidence of disease than females (7M:3F). The reason for this sex bias remains unclear. We hypothesized that this disparity was due to biological differences between the male and female immune response. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy donors were isolated and infected with C. neoformans ± exogenous testosterone or 17-ß-estradiol. C. neoformans, B, T, and NK cell proliferation was quantified by flow cytometry. Cytokine analysis was conducted via protein array or ELISA. Serological testing was conducted to determine previous exposure to C. neoformans. RESULTS: C. neoformans proliferated more in male PBMCs. T cell percentages in both sexes were lower in infected versus uninfected cells. Male PBMCs had lower CD3+, CD4+, and CD8+ T cells percentages during infection compared to females. Cytokine profiles showed differences in uninfected male and female PBMCs, which subsided during infection. Only one donor was sero-negative for prior C. neoformans exposure. There was an effect of estrogen in one dataset. CONCLUSIONS: These results suggest that males show an inherent deficit in T cell response during infection, which may contribute to the increased incidence of disease in males.


Assuntos
Criptococose/imunologia , Cryptococcus neoformans , Leucócitos Mononucleares/microbiologia , Subpopulações de Linfócitos/microbiologia , Adolescente , Proliferação de Células , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Feminino , Humanos , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Contagem de Linfócitos , Subpopulações de Linfócitos/metabolismo , Masculino , Caracteres Sexuais
13.
Sci Rep ; 9(1): 13230, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519925

RESUMO

Inflammation is central to chronic kidney disease (CKD) pathogenesis and vascular outcomes, but the exact players remain unidentified. Since low density granulocytes (LDGs) are emerging mediators in inflammatory conditions, we aimed to evaluate whether LDGs may be altered in CKD and related to clinical outcomes as biomarkers. To his end, LDGs subsets were measured in peripheral blood by flow cytometry and confocal microscopy in 33 CKD patients undergoing peritoneal dialysis and 15 healthy controls (HC). Analyses were replicated in an additional cohort. DEF3 (marker of early granulopoiesis) gene expression on PBMCs was quantified by qPCR. Total CD15+ LDGs and both CD14lowCD16+ and CD14-CD16- subsets were expanded in CKD. The relative frequency of the CD14-CD16- subpopulation was higher among the CD15+ pool in CKD. This alteration was stable over-time. The increased CD14-CD16-CD15+ paralleled Kauppila scores and DEF3 expression, whereas no association was found with CD14lowCD16+ CD15+. Both subsets differed in their CD11b, CD10, CD35, CD31, CD62L, IFNAR1 and CD68 expression, FSC/SSC features and nuclear morphology, pointing to different origins and maturation status. In conclusion, LDGs were expanded in CKD showing a skewed distribution towards a CD14-CD16-CD15+ enrichment, in association with vascular calcification. DEF3 expression in PBMC can be a marker of LDG expansion.

14.
J Asthma Allergy ; 12: 217-233, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496752

RESUMO

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the leading cause of hypersensitivity drug reactions. The different chemical structures, cyclooxygenase 1 (COX-1) and/or COX-2 inhibitors, are taken at all ages and some can be easily obtained over the counter. Vasoactive inflammatory mediators like histamine and leukotriene metabolites can produce local/systemic effects. Responders can be selective (SR), IgE or T-cell mediated, or cross-intolerant (CI). Inhibition of the COX pathway is the common mechanism in CI, with the skin being the most frequent organ involved, followed by the lung and/or the nose. An important number of cases have skin and respiratory involvement, with systemic manifestations ranging from mild to severe anaphylaxis. Among SR, this is the most frequent entity, often being severe. Recent years have seen an increase in reactions involving the skin, with many cases having urticaria and/or angioedema in the absence of chronic urticaria. Aspirin, the classical drug involved, has now been replaced by other NSAIDs, with ibuprofen being the universal culprit. For CI, no in vivo/in vitro diagnostic methods exist and controlled administration is the only option unless the cases evaluated report repetitive and consistent episodes with different NSAIDs. In SR, skin testing (patch and intradermal) with 24-48 reading can be useful, mainly for delayed T-cell responses. Acetyl salicylic acid (ASA) is the test drug to establish the diagnosis and confirm/exclude CI by controlled administration. Desensitization to ASA has been extensively used in respiratory cases though it can also be applied in those cases where it is required.

15.
Parkinsonism Relat Disord ; 66: 195-201, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31473084

RESUMO

INTRODUCTION: Despite clinical relevance and potential role on the disease pathogenesis, underlying mechanisms of constipation in Parkinson's disease (PD) remain poorly understood. A systematic assessment using complementary physiological investigations was performed to elucidate constipation pathophysiology in order to improve its symptomatic management. METHODS: PD patients with constipation were evaluated with clinical questionnaires, colonic transit, high-resolution anorectal manometry and MRI defecography. Results were compared and correlated with clinical features. RESULTS: A total of 42 patients (69% male; age 68 ±â€¯8 years; disease duration 10.5 ±â€¯6.1 years) were included, of whom 33 (78.6%) had objective constipation defined by < 3 bowel movements per week or straining. Severity of constipation measured by self-administered questionnaires correlated with disease severity, burden of motor and non-motor symptoms but not with age, disease duration or Parkinson's medications. Colonic transit and anorectal function (high-resolution anorectal manometry and/or MRI defecography) was assessed in 15 patients. A combination of both delayed colonic transit and anorectal dysfunction was the pattern most commonly found (60% of patients) and overall anorectal dysfunction was more prevalent than isolated slow transit constipation. Physiological findings were heterogeneous including reduced colonic motility, rectal hyposensitivity, defecatory dyssynergia and poor motor rectal function. CONCLUSION: Subjective constipation in PD is poorly correlated with commonly used definition, assessment questionnaires and physiological results. Multiple complex overlapping pathophysiological mechanisms are responsible including slow transit and anorectal dysfunction. Complementary investigations to assess colonic transit and anorectal function are required in those with refractory symptoms for a systematic assessment and appropriate symptomatic management.

16.
Rev. argent. salud publica ; 10(40): 7-13, 30 de septiembre 2019.
Artigo em Espanhol | LILACS, BINACIS, ARGMSAL | ID: biblio-1024360

RESUMO

INTRODUCCIÓN: Es reconocida la efectividad del test del virus del papiloma humano (VPH) para prevenir el cáncer cervicouterino (CC), así como su potencial para reducir barreras de acceso al tamizaje a través de su modalidad autotoma (ATVPH). Uno de los principales desafíos consiste en garantizar el acceso a la citología de triaje de las mujeres con AT-VPH positivas (VPH+). El objetivo de este estudio fue analizar la magnitud y los determinantes sociales de la adherencia al triaje (realización de citología posterior a un resultado de test de VPH+) en mujeres de 30 años o más con AT-VPH+ dentro del sistema público de salud de la provincia de Jujuy. MÉTODOS: Se efectuó un estudio descriptivo transversal con análisis del Sistema de Información para el Tamizaje (SITAM) y encuestas domiciliarias a mujeres de 30 años o más con autotomas positivas en Jujuy durante 2015-2016, sin registro de triaje. RESULTADOS: El porcentaje estimado de adherencia al triaje fue de entre 96% y 81%. Estos porcentajes son menores a los 60 y 120 días de realizada la AT (18% y 35%, respectivamente). Las mujeres con cobertura de obra social/privada y sin condición de hacinamiento poseen mayor probabilidad de adherir al triaje. El principal motivo de no adherencia fueron los problemas con la entrega de resultados. CONCLUSIONES: Pese a los altos niveles de adherencia al triaje, es necesario incorporar intervenciones que mejoren la entrega de resultados y ayuden a enfrentar las barreras socioestructurales


Assuntos
Colo do Útero , Triagem , Recusa do Médico a Tratar
17.
Stud Health Technol Inform ; 264: 763-767, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438027

RESUMO

30% of the Argentinian population and 58% of Plan de Salud HIBA patients are unaware of their HIV status. The Ministry of Health and US Preventive Service Task recommends physicians to assess HIV infection in persons aged 15 to 65. An HIV screening reminder integrated in an electronic health record (EHR) was created using FHIR to represent clinical information and CDS-Hooks to represent the exchange of information with a CDS service. The tool had a 1% intervention rate, and 67.4% acceptance rate. The number of HIV screening tests requested during the weeks after the CDSS implementation and in the same period in 2017 were obtained. 575 orders were requested in the 2017 period and 893 in the 2018. 89 (almost 10%) of these came from the electronic tool. The preliminary results indicate that this non disruptive, action oriented reminder can contribute to increased HIV screening orders.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Infecções por HIV , Adolescente , Adulto , Idoso , Registros Eletrônicos de Saúde , HIV , Infecções por HIV/diagnóstico , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Serviços Preventivos de Saúde , Adulto Jovem
18.
Molecules ; 24(15)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382514

RESUMO

Crocus sativus L. has been cultivated throughout history to obtain its flowers, whose dried stigmas give rise to the spice known as saffron. Crocetin esters, picrocrocin, and safranal are the main metabolites of this spice, which possess a great bioactivity, although the mechanisms of action and its bioavailability are still to be solved. The rest of the flower is composed by style, tepals, and stamens that have other compounds, such as kaempferol and delphinidin, which have an important antioxidant capacity, and these can be applied in foods, phytopharmaceuticals, and cosmetics. The aim of this work was to provide an updated and critical review of the research on the main compounds of Crocus sativus L. flower, including the adequate analytical methods for their identification and quantification, with a focus on their bioactivity and bioavailability.


Assuntos
Crocus/química , Flores/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Disponibilidade Biológica , Estrutura Molecular , Fenóis/química , Fenóis/farmacologia , Fenótipo , Relação Estrutura-Atividade
19.
Front Genet ; 10: 582, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293618

RESUMO

The prevalence of allergic diseases and drug hypersensitivity reactions (DHRs) during recent years is increasing. Both, allergic diseases and DHRs seem to be related to an interplay between environmental factors and genetic susceptibility. In recent years, a large effort in the elucidation of the genetic mechanisms involved in these disorders has been made, mostly based on case-control studies, and typically focusing on isolated SNPs. These studies provide a limited amount of information, which now can be greatly expanded by the complete coverage that Next Generation Sequencing techniques offer. In this study, we analyzed the promoters of sixteen genes related to the Vitamin D pathway and the high-affinity IgE receptor, including FCER1A, MS4A2, FCER1G, VDR, GC, CYP2R1, CYP27A1, CYP27B1, CYP24A1, RXRA, RXRB, RXRG, IL4, IL4R, IL13, and IL13RA1. The study group was composed of patients with allergic rhinitis plus asthma (AR+A), patients with hypersensitivity to beta-lactams (BLs), to NSAIDs including selective hypersensitivity (SH) and cross-reactivity (CR), and healthy controls without antecedents of atopy or adverse drug reactions. We identified 148 gene variations, 43 of which were novel. Multinomial analyses revealed that three SNPs corresponding to the genes FCER1G (rs36233990 and rs2070901), and GC (rs3733359), displayed significant associations and, therefore, were selected for a combined dataset study in a cohort of 2,476 individuals. The strongest association was found with the promoter FCER1G rs36233990 SNP that alters a transcription factor binding site. This SNP was over-represented among AR+A patients and among patients with IgE-mediated diseases, as compared with control individuals or with the rest of patients in this study. Classification models based on the above-mentioned SNPs were able to predict correct clinical group allocations in patients with DHRs, and patients with IgE-mediated DHRs. Our findings reveal gene promoter SNPs that are significant predictors of drug hypersensitivity, thus reinforcing the hypothesis of a genetic predisposition for these diseases.

20.
Nat Commun ; 10(1): 2955, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273203

RESUMO

Dendritic cells (DCs), a vital component of the innate immune system, are considered to lack antigen specificity and be devoid of immunological memory. Strategies that can induce memory-like responses from innate cells can be utilized to elicit protective immunity in immune deficient persons. Here we utilize an experimental immunization strategy to modulate DC inflammatory and memory-like responses against an opportunistic fungal pathogen that causes significant disease in immunocompromised individuals. Our results show that DCs isolated from protectively immunized mice exhibit enhanced transcriptional activation of interferon and immune signaling pathways. We also show long-term memory-like cytokine responses upon subsequent challenge with the fungal pathogen that are abrogated with inhibitors of specific histone modifications. Altogether, our study demonstrates that immunization strategies can be designed to elicit memory-like DC responses against infectious disease.


Assuntos
Células Dendríticas/imunologia , Memória Imunológica , Animais , Criptococose/imunologia , Criptococose/microbiologia , Cryptococcus/fisiologia , Células Dendríticas/microbiologia , Feminino , Histonas/metabolismo , Imunidade Inata , Inflamação/genética , Inflamação/patologia , Interferon gama/metabolismo , Pulmão/imunologia , Pulmão/microbiologia , Camundongos Endogâmicos BALB C , Fenótipo , Processamento de Proteína Pós-Traducional , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Vacinação
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