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1.
Nat Immunol ; 17(1): 65-75, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26595887

RESUMO

Viral respiratory tract infections are the main causative agents of the onset of infection-induced asthma and asthma exacerbations that remain mechanistically unexplained. Here we found that deficiency in signaling via type I interferon receptor led to deregulated activation of group 2 innate lymphoid cells (ILC2 cells) and infection-associated type 2 immunopathology. Type I interferons directly and negatively regulated mouse and human ILC2 cells in a manner dependent on the transcriptional activator ISGF3 that led to altered cytokine production, cell proliferation and increased cell death. In addition, interferon-γ (IFN-γ) and interleukin 27 (IL-27) altered ILC2 function dependent on the transcription factor STAT1. These results demonstrate that type I and type II interferons, together with IL-27, regulate ILC2 cells to restrict type 2 immunopathology.


Assuntos
Imunidade Inata/imunologia , Interferon Tipo I/imunologia , Linfócitos/imunologia , Infecções Respiratórias/imunologia , Animais , Citocinas/biossíntese , Citocinas/imunologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infecções por Orthomyxoviridae/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Infecções Respiratórias/patologia
2.
Phytopathology ; 112(9): 2012-2021, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35302895

RESUMO

Plum pox virus (PPV) causes sharka disease in Prunus trees. Peach (P. persica) trees are severely affected by PPV, and no definitive source of genetic resistance has been identified. However, previous results showed that PPV-resistant 'Garrigues' almond (P. dulcis) was able to transfer its resistance to 'GF305' peach through grafting, reducing symptoms and viral load in PPV-infected plants. A recent study tried to identify genes responsible for this effect by studying messenger RNA expression through RNA sequencing in peach and almond plants, before and after grafting and before and after PPV infection. In this work, we used the same peach and almond samples but focused the high-throughput analyses on small RNA (sRNA) expression. We studied massive sequencing data and found an interesting pattern of sRNA overexpression linked to antiviral defense genes that suggested activation of these genes followed by downregulation to basal levels. We also discovered that 'Garrigues' almond plants were infected by different plant viruses that were transferred to peach plants. The large amounts of viral sRNA found in grafted peaches indicated a strong RNA silencing antiviral response and led us to postulate that these plant viruses could be collaborating in the observed "Garrigues effect."


Assuntos
Vírus Eruptivo da Ameixa , Prunus dulcis , Prunus persica , Antivirais , Doenças das Plantas , Vírus Eruptivo da Ameixa/genética , Prunus dulcis/genética , Prunus persica/genética , Interferência de RNA , Árvores
3.
Int J Mol Sci ; 23(9)2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35562966

RESUMO

This study aimed at the monitoring of the apricot (Prunus armeniaca L.) ripening progression through the expression analysis of 25 genes related to fruit quality traits in nine cultivars with great differences in fruit color and ripening date. The level of pigment compounds, such as anthocyanins and carotenoids, is a key factor in food taste, and is responsible for the reddish blush color or orange skin and flesh color in apricot fruit, which are desirable quality traits in apricot breeding programs. The construction of multiple linear regression models to predict anthocyanins and carotenoids content from gene expression allows us to evaluate which genes have the strongest influence over fruit color, as these candidate genes are key during biosynthetic pathways or gene expression regulation, and are responsible for the final fruit phenotype. We propose the gene CHS as the main predictor for anthocyanins content, CCD4 and ZDS for carotenoids content, and LOX2 and MADS-box for the beginning and end of the ripening process in apricot fruit. All these genes could be applied as RNA markers to monitoring the ripening stage and estimate the anthocyanins and carotenoids content in apricot fruit during the ripening process.


Assuntos
Prunus armeniaca , Antocianinas/genética , Antocianinas/metabolismo , Carotenoides/metabolismo , Frutas/metabolismo , Expressão Gênica , Melhoramento Vegetal , Prunus armeniaca/genética , Prunus armeniaca/metabolismo
4.
Eur J Immunol ; 50(11): 1676-1690, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32557554

RESUMO

Monocyte maturation program into macrophages (MΦ) is well defined in murine gut under homeostatic or inflammatory conditions. Obviously, in vivo tracking of monocytes in inflamed tissues remains difficult in humans. Furthermore, in vitro models fall short in generating the surrogates of transient extravasated tissue inflammatory monocytes. Here, we aimed to unravel environmental cues that replicated the human monocyte "waterfall" process in vitro by first, generating tissue-like inflammatory monocytes, which were then shifted toward MΦ. Purified CD14+ CD16- monocytes, cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-γ and IL23, differentiated into CD14+ CD163- cells that displayed a monocyte-like morphology. In vitro generated inflammatory CD14+ CD163- (inflammatory monocyte-like cells) cells promoted IL-1ß-dependent memory Th17 and Th17/Th1 responses, like the CD14+ CD163- mo-like cells that accumulate in inflamed colon of Crohn's disease patients. Next, in vitro generated inflammatory monocyte-like cells converted to functional CD163+ MΦ following exposure to TGF-ß and IL10. Gene set enrichment analysis further revealed a shared molecular signature between converted CD163+ MΦ and MΦ detected in various inflamed nonlymphoid and lymphoid diseased tissues. Our findings propose a two-step in vitro culture that recapitulates human monocyte maturation cascade in inflamed tissue. Manipulation of this process might open therapeutic avenues for chronic inflammatory disorders.


Assuntos
Inflamação/patologia , Macrófagos/citologia , Monócitos/citologia , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Diferenciação Celular/fisiologia , Células Cultivadas , Técnicas de Cocultura/métodos , Colo/citologia , Colo/metabolismo , Humanos , Inflamação/metabolismo , Interleucina-10/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Camundongos , Monócitos/metabolismo , Receptores de Superfície Celular/metabolismo , Células Th1/citologia , Células Th1/metabolismo , Células Th17/citologia , Células Th17/metabolismo , Fator de Crescimento Transformador beta/metabolismo
5.
Int J Mol Sci ; 22(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808287

RESUMO

No natural sources of resistance to Plum pox virus (PPV, sharka disease) have been identified in peach. However, previous studies have demonstrated that grafting a "Garrigues" almond scion onto "GF305" peach rootstock seedlings heavily infected with PPV can progressively reduce disease symptoms and virus accumulation. Furthermore, grafting a "Garrigues" scion onto the "GF305" rootstock has been shown to completely prevent virus infection. This study aims to analyse the rewiring of gene expression associated with this resistance to PPV transmitted by grafting through the phloem using RNA-Seq and RT-qPCR analysis. A total of 18 candidate genes were differentially expressed after grafting "Garrigues" almond onto healthy "GF305" peach. Among the up-regulated genes, a HEN1 homolog stands out, which, together with the differential expression of RDR- and DCL2-homologs, suggests that the RNA silencing machinery is activated by PPV infection and can contribute to the resistance induced by "Garrigues" almond. Glucan endo-1,3-beta D-glucosidase could be also relevant for the "Garrigues"-induced response, since its expression is much higher in "Garrigues" than in "GF305". We also discuss the potential relevance of the following in PPV infection and "Garrigues"-induced resistance: several pathogenesis-related proteins; no apical meristem proteins; the transcription initiation factor, TFIIB; the speckle-type POZ protein; in addition to a number of proteins involved in phytohormone signalling.


Assuntos
Resistência à Doença/genética , Prunus dulcis/genética , Prunus persica/genética , Produção Agrícola/métodos , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Técnicas Genéticas , Melhoramento Vegetal/métodos , Doenças das Plantas/virologia , Reguladores de Crescimento de Plantas , Vírus Eruptivo da Ameixa/genética , Prunus/genética , Interferência de RNA , Transdução de Sinais/genética
6.
Rev Esp Enferm Dig ; 113(9): 684-685, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33618534

RESUMO

We would like to congratulate Drs. Espinel and Pinedo for their excellent results in single-ballon enteroscopy-assisted ERCP recently published in REED(1).We also want to share our experience. Between 2015 and 2021 we have performed 31 procedures in 26 patients. Half of the procedures (45.16%) were performed in patients with Roux-en-Y hepatic jejunostomy. Eight of these (22.80%) had prior primary bile duct surgery and six (19.35%) had prior Whipple surgery. The other half of the procedures (54.8%) presented native papilla: 10 (32.25%) subtotal gastrectomy and seven (22.58%) gastric bypass surgery.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Enteroscopia de Balão Único , Anastomose em-Y de Roux , Gastrectomia , Humanos , Estudos Retrospectivos
7.
Int J Mol Sci ; 22(1)2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33396946

RESUMO

In plants, fruit ripening is a coordinated developmental process that requires the change in expression of hundreds to thousands of genes to modify many biochemical and physiological signal cascades such as carbohydrate and organic acid metabolism, cell wall restructuring, ethylene production, stress response, and organoleptic compound formation. In Prunus species (including peaches, apricots, plums, and cherries), fruit ripening leads to the breakdown of complex carbohydrates into sugars, fruit firmness reductions (softening by cell wall degradation and cuticle properties alteration), color changes (loss of green color by chlorophylls degradation and increase in non-photosynthetic pigments like anthocyanins and carotenoids), acidity decreases, and aroma increases (the production and release of organic volatile compounds). Actually, the level of information of molecular events at the transcriptional, biochemical, hormonal, and metabolite levels underlying ripening in Prunus fruits has increased considerably. However, we still poorly understand the molecular switch that occurs during the transition from unripe to ripe fruits. The objective of this review was to analyze of the molecular bases of fruit quality in Prunus species through an integrated metabolic, genomic, transcriptomic, and epigenetic approach to better understand the molecular switch involved in the ripening process with important consequences from a breeding point of view.


Assuntos
Qualidade dos Alimentos , Frutas/química , Metaboloma , Melhoramento Vegetal , Proteínas de Plantas/metabolismo , Prunus/química , Transcriptoma , Frutas/genética , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Proteínas de Plantas/genética , Prunus/genética , Prunus/crescimento & desenvolvimento , Prunus/metabolismo
8.
Behav Genet ; 47(6): 596-608, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28879499

RESUMO

Neurexins and neuroligins are neuronal membrane adhesion molecules that have been involved in neuropsychiatric and neurodevelopmental disorders. The nrx-1 and nlg-1 genes of Caenorhabditis elegans encode NRX-1 and NLG-1, orthologue proteins of human neurexins and neuroligins, respectively. Dopaminergic and serotoninergic signalling control the locomotory rate of the nematode. When well-fed animals are transferred to a plate with food (bacterial lawn), they reduce the locomotory rate. This behavior, which depends on dopamine, is known as basal slowing response (BSR). Alternatively, when food-deprived animals are moved to a plate with a bacterial lawn, further decrease their locomotory rate. This behavior, known as enhanced slowing response (ESR), is serotonin dependent. C. elegans nlg-1-deficient mutants are impaired in BSR and ESR. Here we report that nrx-1-deficient mutants were defective in ESR, but not in BSR. The nrx-1;nlg-1 double mutant was impaired in both behaviors. Interestingly, the nlg-1 mutants upregulate the expression of comt-4 which encodes an enzyme with putative catechol-O-methyltransferase activity involved in dopamine degradation. Our study also shows that comt-4(RNAi) in nlg-1-deficient mutants rescues the wild type phenotypes of BSR and ESR. On the other hand, comt-4(RNAi) in nlg-1-deficient mutants also recovers, at least partially, the gentle touch response and the pharyngeal pumping rate that were impaired in these mutants. These latter behaviors are dopamine and serotonin dependent, respectively. Based on these results we propose a model for the neuroligin function in modulating the dopamine-dependent locomotory behavior in the nematode.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Moléculas de Adesão Celular Neuronais/genética , Moléculas de Adesão Celular Neuronais/metabolismo , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Catecol O-Metiltransferase/genética , Catecol O-Metiltransferase/metabolismo , Catecol O-Metiltransferase/fisiologia , Dopamina/metabolismo , Locomoção/genética , Locomoção/fisiologia , Interferência de RNA , Serotonina/metabolismo
9.
Age Ageing ; 46(1): 119-124, 2017 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-28181648

RESUMO

Background: Faecal impaction (FI) is a common problem in old people living in nursing home. Its prevalence and associated factors remain unknown in the general population. Aim: To evaluate FI prevalence in the Spanish population older than 65 years and to assess the factors associated with it. Methods: A telephone survey was carried out of a Spanish population older than 65 years random sample (N = 1000). FI was assessed using a previously validated questionnaire. Results: A total of 28,128 calls were made; 1,431 subjects were eligible and 1,000 subjects were enrollled, mean aged 74.6 ± 7.3 (65­97); 57.5% were women. At least 53 people reported FI within the past year (5.3% (CI 95%: 3.9­6.7%)). Only 0.03% met criteria for chronic constipation and faecal incontinence. FI-associated factors were constipation, female gender, reduced physical activity, and chronic renal failure (CRF). Conclusion: FI is a prevalent problem in old Spanish population. Constipation and female gender are the main associated factors; low physical activity and CRF appear to play also a significant role. Further studies are required to confirm this association.


Assuntos
Impacção Fecal/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Comorbidade , Constipação Intestinal/epidemiologia , Impacção Fecal/diagnóstico , Impacção Fecal/fisiopatologia , Incontinência Fecal/epidemiologia , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Falência Renal Crônica/epidemiologia , Masculino , Prevalência , Fatores de Risco , Comportamento Sedentário , Fatores Sexuais , Espanha/epidemiologia
10.
Int J Clin Pract ; 71(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28949430

RESUMO

AIM: We analysed the effectiveness and safety of outpatient parenteral antibiotic therapy (OPAT) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in patients admitted to home hospitalisation units (HHU). METHODS: Retrospective multicentre study of patients with AECOPD included in the Spanish OPAT Registry during 2 years period. RESULTS: Twenty-seven hospitals included 562 episodes in 361 patients diagnosed COPD GOLD III-IV. The most frequently isolated pathogen was Pseudomonas aeruginosa (38%) and the most frequently used antibiotic was piperacillin-tazobactam (20%). The effectiveness of OPAT defined as the rate of improvement or recovery was 93.4%. The safety of OPAT defined as no adverse drug events and no infectious or catheter-related complications was 89.3%. Moreover, the risk of hospital readmission was not greater in patients with AECOPD aged >80 years. No differences in the effectiveness or safety were observed when OPAT was administered by patients and/or caregivers. CONCLUSION: Patients with AECOPD who require parenteral antimicrobial therapy can be managed effectively and safely in HHU, avoiding hospital stays, readmissions and complications.


Assuntos
Anti-Infecciosos/uso terapêutico , Serviços de Assistência Domiciliar , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Administração Intravenosa , Idoso , Assistência Ambulatorial , Feminino , Humanos , Masculino , Infecções Respiratórias/microbiologia , Espanha
11.
J Clin Gastroenterol ; 50(3): 202-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26084009

RESUMO

BACKGROUND: Although 2% to 4% of the population develop gastroesophageal reflux disease (GERD) annually, factors associated with the onset of GERD are scarcely known. OBJECTIVE: To assess whether such factors include weight gain and psychological distress. METHODS: Two cohorts (first: N=222; second N=754) drawn from 2 case-control studies were followed up for around 5 years. In 2004, all participants were directly interviewed using a validated questionnaire to collect data on body weight, height, GERD symptoms, and psychological distress. In 2009 to 2010, these same participants were again interviewed using the same methodology. RESULTS: The response rate was 83.3% in cohort 1 and 39.1% in cohort 2, after a follow-up of 4.3±0.7 and 5.6±0.3 years, respectively. The multivariate analysis showed only weight gain and psychological distress as being independently associated with the onset of GERD in both cohorts. Weight gain per kilogram showed an adjusted odds ratio (OR) of 1.21 (1.01-1.44) in the first cohort, and a gain of 5 kg or more showed an adjusted OR of 4.65 (1.72-12.53) in the second. Somatization scores showed an adjusted OR of 1.09 (1.04-1.15) in the first cohort (measured as Minnesota Multiphasic Personality Inventory 2 hypochondriasis score) and 2.88 (1.04-8.02) in the second (measured as psychosomatic symptoms score). Body mass index on attaining overweight or obese status was associated with the onset of GERD in the unadjusted but not in the adjusted analysis. CONCLUSIONS: Weight gain and somatization are the main factors associated with the onset of GERD. The association between GERD and obesity is just the ultimate consequence of gaining weight.


Assuntos
Refluxo Gastroesofágico/epidemiologia , Hipocondríase/epidemiologia , Estresse Psicológico/epidemiologia , Aumento de Peso , Adulto , Índice de Massa Corporal , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Adulto Jovem
12.
J Allergy Clin Immunol ; 136(2): 351-9.e1, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25792465

RESUMO

BACKGROUND: Psoriasis is a systemic inflammatory disease in which IL-17 and IL-22 levels are markedly increased in the skin and blood. The prevalent concept, using skin cells that are isolated from psoriatic plaques and examined after cell expansion and in vitro stimulation, is that IL-17 and IL-22 production essentially results from T cells and the rare type 3 innate lymphoid cells. OBJECTIVE: We sought to examine the cellular source of IL-17A and IL-22 at the protein and transcriptional single-cell level immediately after ex vivo skin cell isolation from psoriatic plaques. METHODS: Skin biopsy specimens were collected from patients with psoriasis, as well as from patients with atopic dermatitis. Cell suspensions were prepared by combining mild enzymatic digestion and mechanical dissociation and analyzed for cytokine expression without prior in vitro culture and stimulation. Expression of IL-17 and IL-22 was quantified at the protein and mRNA single-cell level by using flow cytometry. RESULTS: IL-22 is predominantly expressed by CD3(-)c-Kit(+) cells relative to CD3(+) T cells in lesional skin of patients with psoriasis and patients with atopic dermatitis. Strikingly, we identified c-Kit(+)FcεRI(+) mast cells as major IL-22 producers. The proportion of mast cells that produce IL-22 ranges from 20% to 80% in patients with psoriasis or those with atopic dermatitis. Skin mast cells express IL-22 and IL-17 mRNA. Conversely, IL-17-producing T cells outnumber IL-17-producing mast cells, which also express IL-17 receptor. CONCLUSION: Human skin mast cells are previously unrecognized IL-22 producers. We further established that skin mast cells express IL-17. Thus mast cells might play an important role in the physiopathology of chronic inflammatory skin disorders.


Assuntos
Dermatite Atópica/imunologia , Interleucina-17/imunologia , Interleucinas/imunologia , Mastócitos/imunologia , Psoríase/imunologia , Linfócitos T/imunologia , Complexo CD3/genética , Complexo CD3/imunologia , Contagem de Células , Dermatite Atópica/genética , Dermatite Atópica/patologia , Expressão Gênica , Humanos , Interleucina-17/genética , Interleucinas/genética , Mastócitos/patologia , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/imunologia , Psoríase/genética , Psoríase/patologia , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Receptores de IgE/genética , Receptores de IgE/imunologia , Receptores de Interleucina-17/genética , Receptores de Interleucina-17/imunologia , Pele/imunologia , Pele/patologia , Linfócitos T/patologia , Interleucina 22
13.
Molecules ; 20(10): 19372-92, 2015 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-26512637

RESUMO

ß-Glucosidase (EC 3.2.1.21) is a prominent member of the GH1 family of glycoside hydrolases. The properties of this ß-glucosidase appear to include resistance to temperature, urea, and iodoacetamide, and it is activated by 2-ME, similar to other members. ß-Glucosidase from chayote (Sechium edule) was purified by ionic-interchange chromatography and molecular exclusion chromatography. Peptides detected by LC-ESI-MS/MS were compared with other ß-glucosidases using the BLAST program. This enzyme is a 116 kDa protein composed of two sub-units of 58 kDa and shows homology with Cucumis sativus ß-glucosidase (NCBI reference sequence XP_004154617.1), in which seven peptides were found with relative masses ranging from 874.3643 to 1587.8297. The stability of ß-glucosidase depends on an initial concentration of 0.2 mg/mL of protein at pH 5.0 which decreases by 33% in a period of 30 h, and then stabilizes and is active for the next 5 days (pH 4.0 gives similar results). One hundred µg/mL ß-D-glucose inhibited ß-glucosidase activity by more than 50%. The enzyme had a Km of 4.88 mM with p-NPG and a Kcat of 10,000 min(-1). The optimal conditions for the enzyme require a pH of 4.0 and a temperature of 50 °C.


Assuntos
Cucurbitaceae/enzimologia , beta-Glucosidase/isolamento & purificação , Sequência de Aminoácidos , Precipitação Química , Cromatografia por Troca Iônica , Estabilidade Enzimática , Glucose/química , Concentração de Íons de Hidrogênio , Cinética , Dados de Sequência Molecular , Proteínas de Plantas , Homologia de Sequência de Aminoácidos , Especificidade por Substrato , beta-Glucosidase/química
14.
Blood ; 120(24): 4761-71, 2012 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-23071273

RESUMO

Basophils are a rare population of granulocytes that have long been associated with IgE-mediated and Th2-associated allergic diseases. However, the role of basophils in Th17 and/or Th1 diseases has not been reported. In the present study, we report that basophils can be detected in the mucosa of Th17-associated lung and inflammatory bowel disease and accumulate in inflamed colons containing large quantities of IL-33. We also demonstrate that circulating basophils increased memory Th17 responses. Accordingly, IL-3- or IL-33-activated basophils amplified IL-17 release in effector memory T cells (T(EM)), central memory T cells (T(CM)), and CCR6(+) CD4 T cells. More specifically, basophils promoted the emergence of IL-17(+)IFN-γ(-) and IL-17(+)IFN-γ(+), but not IL-17(-)IFN-γ(+) CD4 T cells in T(EM) and T(CM). Mechanistic analysis revealed that the enhancing effect of IL-17 production by basophils in T(EM) involved the ERK1/2 signaling pathway, occurred in a contact-independent manner, and was partially mediated by histamine via H(2) and H(4) histamine receptors. The results of the present study reveal a previously unknown function for basophils in augmenting Th17 and Th17/Th1 cytokine expression in memory CD4 T cells. Because basophils accumulated in inflamed inflammatory bowel disease tissues, we propose that these cells are key players in chronic inflammatory disorders beyond Th2.


Assuntos
Basófilos/imunologia , Linfócitos T CD4-Positivos/imunologia , Comunicação Celular/imunologia , Interleucina-17/imunologia , Células Th17/imunologia , Basófilos/metabolismo , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Células Cultivadas , Técnicas de Cocultura , Citometria de Fluxo , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Histamina/imunologia , Histamina/metabolismo , Humanos , Memória Imunológica/imunologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-17/metabolismo , Interleucina-3/imunologia , Interleucina-3/farmacologia , Interleucina-33 , Interleucinas/imunologia , Interleucinas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/imunologia , Pneumonia/imunologia , Pneumonia/metabolismo , Pneumonia/patologia , Receptores Histamínicos H2/genética , Receptores Histamínicos H2/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Th17/efeitos dos fármacos , Células Th17/metabolismo
15.
BMC Gastroenterol ; 14: 17, 2014 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-24450939

RESUMO

BACKGROUND: Scales for aiding physicians diagnose gastro-oesophageal reflux disease (GERD) have not been evaluated in terms of their ability to discriminate between troublesome symptoms (TS) and non-troublesome symptoms (NTS). Our objective is to evaluate the ability of the Reflux Disease Questionnaire (RDQ) to identify GERD according to referral of TS, in patients without previous proton pump inhibitor (PPI) treatment and in patients on PPI treatment. METHODS: Patients consulting physicians because of heartburn or acid regurgitation were recruited at 926 primary-care centres in Spain. They were asked to complete several questionnaires including the RDQ, and to define which of their symptoms were troublesome. Information on drug treatment was collected by the physician. We performed a receiver operating characteristic (ROC) curve analysis to ascertain the RDQ's optimum cut-point for identifying TS. RESULTS: 4574 patients were included, 1887 without PPI and 2596 on PPI treatment. Among those without PPI treatment, 1722 reported TS. The area under the curve (AUC) was 0.79 for the RDQ, and the optimum RDQ cut-point for identifying TS was 3.18 (sensitivity, 63.2%; specificity, 80.2%). A total of 2367 patients on PPI treatment reported TS, and the optimum RDQ cut-off value was 3.06 (sensitivity, 65.4%; specificity, 71.8%). CONCLUSIONS: An RDQ score higher than 3 shows good sensitivity and specificity for differentiating TS from NTS among patients without PPI or on PPI treatment. The RDQ is useful in primary care for diagnosis of GERD based on the Montreal definition.


Assuntos
Refluxo Gastroesofágico/diagnóstico , Inquéritos e Questionários , Adulto , Área Sob a Curva , Estudos Transversais , Feminino , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/tratamento farmacológico , Azia/etiologia , Humanos , Refluxo Laringofaríngeo/etiologia , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons , Curva ROC , Espanha
16.
J Immunol ; 188(9): 4249-55, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22461697

RESUMO

T cell memory is the hallmark of adaptive immunity. Central questions are to determine which cells among proliferating effector T cells will live beyond the crash of the immune response (IR) and develop into functional memory T cells. CD47, considered as a marker of self, is implicated in cell death, cell elimination, and in the inflammatory response. We report in this article that CD47 expression was transiently regulated on Ag-specific CD4 T cells, that is, from CD47(high) to CD47(low) to CD47(high), during the course of the in vivo IR. Specifically, CD47(high) status marked central memory CD4 T cell precursors at an early time point of the IR. By contrast, cytokine production was a functional attribute restricted to CD47(high), but not CD47(low), polyclonal effector CD4 T cells during recall responses in an experimental model of chronic airway inflammatory disease. Passive transfer of CD47(high), but not CD47(low), CD4 T cells in nonlymphopenic naive mice generated long-lived memory T cells capable of anamnestic responses. We conclude that CD47(high) status on CD4 T cells identifies functional long-lived memory T cell progenitors.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Antígeno CD47/imunologia , Regulação da Expressão Gênica/fisiologia , Imunidade Celular/fisiologia , Memória Imunológica/fisiologia , Células Precursoras de Linfócitos T/imunologia , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/metabolismo , Antígeno CD47/biossíntese , Antígeno CD47/genética , Camundongos , Camundongos Knockout , Células Precursoras de Linfócitos T/citologia , Células Precursoras de Linfócitos T/metabolismo
17.
Neurogenetics ; 14(3-4): 233-42, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24100941

RESUMO

Neuroligins are neuronal and neuromuscular transmembrane proteins that have been implicated in autism spectrum disorder and other cognitive diseases. The nlg-1 gene from Caenorhabditis elegans is orthologous to human neuroligin genes. In the nematode, the locomotory rate is mediated by dopaminergic and serotonergic pathways, which result in two different behavioral responses known as basal slowing response (BSR) and enhanced slowing response (ESR), respectively. We report that nlg-1-deficient mutants are defective in both the BSR and ESR behaviors. In addition, we demonstrate that methylphenidate (a dopamine reuptake inhibitor) and fluoxetine (a serotonin reuptake inhibitor), two drugs widely used for the treatment of behavioral disorders in humans, are able to restore the BSR and ESR wild type phenotypes, respectively, in nlg-1 defective mutant nematodes. The abnormal locomotory behavior patterns were rescued in nlg-1-deficient mutant by expressing a cDNA from the human NLGN1 gene under the C. elegans nlg-1 promoter. However, human NLGN1 (R453C) and NLGN1 (D432X) mutant alleles did not rescue any of the two mutant phenotypes. The results indicate that neuroligin is involved in modulating the action of dopamine and serotonin in the nematode and suggest that the functional mechanism underpinning both methylphenidate and fluoxetine in C. elegans might be comparable to that in humans. The neuroligin-deficient mutants may undergo inefficient synaptic transmissions which could affect different traits in the nervous system. In particular, neuroligin might be required for normal neurotransmitters release. The understanding of the mechanisms by which methylphenidate and fluoxetine are able to restore the behavior of these mutants could help to explain the etiology of some human neurological diseases.


Assuntos
Moléculas de Adesão Celular Neuronais/fisiologia , Dopamina/metabolismo , Locomoção/fisiologia , Serotonina/metabolismo , Animais , Caenorhabditis elegans , Moléculas de Adesão Celular Neuronais/genética , Inibidores da Captação de Dopamina/farmacologia , Fluoxetina/farmacologia , Locomoção/efeitos dos fármacos , Metilfenidato/farmacologia , Vias Neurais/fisiologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia
18.
Plant Cell Environ ; 36(3): 640-54, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22913613

RESUMO

Sharka, a disease caused by plum pox virus (PPV), has a significant economic impact on fruit tree production. In this work, we analysed the effect of (2,1,3)-benzothiadiazole (BTH) and L-2-oxo-4-thiazolidine-carboxylic acid (OTC) on plant growth and virus content. OTC reduced sharka symptom, stimulated plant growth and alleviated PPV-induced oxidative stress, indicated by a lack of changes in some oxidative stress parameters. PPV infection reduced chloroplast electron transport efficiency. However, in the presence of BTH or OTC, no changes in the chlorophyll fluorescence parameters were observed. PPV produced an alteration in chloroplast ultrastructure, giving rise to a decrease in starch contents that was less dramatic in OTC-treated plants. Furthermore, PPV reduced the abundance of proteins associated with photosynthesis, carbohydrate and amino acid metabolism and photorespiration. These changes did not take place in OTC-treated plants, and increases in the expression of proteins related with the aforementioned processes, including ADP-glucose pyrophosphorylase, were produced, which correlated with the lower decrease in starch contents observed in PPV-infected plants treated with OTC. The results suggested that OTC treatment provides protection to the photosynthetic machinery and/or the chloroplast metabolism in PPV-infected peaches. Thus, OTC could have practical implications in agriculture in improving the vigour of different plant species as well as in immunizing plants against pathogens.


Assuntos
Cloroplastos/metabolismo , Vírus Eruptivo da Ameixa , Proteoma , Prunus/virologia , Ácido Pirrolidonocarboxílico , Tiazolidinas , Antioxidantes/metabolismo , Clorofila/metabolismo , Cloroplastos/ultraestrutura , Interações Hospedeiro-Patógeno , Estresse Oxidativo , Doenças das Plantas , Prunus/fisiologia , Prunus/ultraestrutura
19.
BMC Geriatr ; 13: 24, 2013 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-23496919

RESUMO

BACKGROUND: Studies on the epidemiology of fecal impaction are limited by the absence of a valid and reliable instrument to identify the condition in the elderly. Our aim is to validate a questionnaire for identifying fecal impaction in the elderly and to assess the impact of cognitive impairment and the aid of a proxy on its reliability. METHODS: We developed a 5 questions' questionnaire. The questionnaire was presented to twenty doctors to test its face validity. Feasibility was pre-tested with ten non institutionalized subjects who completed the questionnaire twice, once alone or with the help of a proxy, and another along with the researcher.For the validation of the questionnaire all residents in a single nursing-home were invited to participate, allowing the self-decision of using a proxy. Medical records of all subjects were abstracted without knowledge of subjects' answers and agreement between fecal impaction according to self-reported and medical records analyzed. Physical impairment was measured with the Barthel's test and cognitive impairment with the mini-mental test. RESULTS: In the face validity only minor changes in wording were suggested. In the feasibility pre-test all subjects were able to understand and complete the questionnaire and all questions were considered appropriate and easily understandable.One-hundred and ninety-nine of the 244 residents participated in the study (mean age 86,1 ± 6,6). One hundred and forty two subjects understood all questions; not understanding them was inversely associated with cognitive impairment score (aOR: 0.86; 95% CI: 0.82-0.91). One hundred and sixty decided to use a proxy; the use of a proxy was inversely associated with educative level (0.13 (0.02-0.72), minimental's score (0.85; 0.76-0.95) and Barthel's score (0.96; 0.94-0.99). Agreement between medical records and self-completed questionnaire was 85.9% (kappa 0.72 (0,62- 0,82). Disagreement was unrelated to education and cognitive impairment. CONCLUSIONS: Our simple questionnaire is reliable for identifying fecal impaction in the elderly by self-report. Limitation imposed by cognitive impairment is minimized with the aid of a proxy.


Assuntos
Transtornos Cognitivos/diagnóstico , Impacção Fecal/diagnóstico , Procurador , Autorrelato/normas , Inquéritos e Questionários/normas , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/psicologia , Impacção Fecal/epidemiologia , Impacção Fecal/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Casas de Saúde/normas , Procurador/psicologia
20.
Hepatobiliary Pancreat Dis Int ; 12(1): 87-93, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23392804

RESUMO

BACKGROUND: Despite a number of studies show the superiority of early over delayed cholecystectomy in the treatment of acute cholecystitis, there is still controversy over the time for intervention. This study aimed to assess the use of early versus delayed cholecystectomy for the treatment of acute cholecystitis in terms of complications, conversion to open surgery and mean hospital stay. METHOD: We collected patients with acute cholecystitis treated at a referral center for a year, and retrospectively analyzed the chosen therapeutic approach, the percentage of conversion of early cholecystectomy to open surgery, appearance of surgical complications, and mean hospital stay. RESULTS: The study included 117 patients, 44 women and 73 men, who had a mean age of 67.36+/-15.74 years. Early cholecystectomy was chosen in 31 (26.5%) and delayed cholecystectomy in 74 patients (63.2%). Of the 74 patients, 28 (37.8%) required emergency performance of delayed cholecystectomy, and 19 (25.7%) had not undergone surgery by the end of the study. While no differences were observed between early and delayed cholecystectomy in terms of surgical complications and conversion to open surgery, mean hospital stay was nevertheless significantly shorter in the early versus the delayed cholecystectomy group (8.32+/-4.98 vs 15.96+/-8.89 days). CONCLUSION: Under the routine working conditions of a hospital that is neither specially dedicated to the surgical treatment of acute cholecystitis nor provided with specific management guidelines, early cholecystectomy can reduce the hospital stay without increase of the conversion rate or complications.


Assuntos
Colecistectomia Laparoscópica/estatística & dados numéricos , Colecistite Aguda/epidemiologia , Colecistite Aguda/cirurgia , Centros de Atenção Terciária/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Conversão para Cirurgia Aberta/estatística & dados numéricos , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Serviços Médicos de Emergência/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Espanha/epidemiologia , Fatores de Tempo , Resultado do Tratamento
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