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1.
Emerg Med Clin North Am ; 40(1): 119-133, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34782083

RESUMO

Scombroid poisoning, systemic mastocytosis, and hereditary alpha tryptasemia all present with episodes that resemble allergic reactions. Knowledge regarding systemic mastocytosis and hereditary alpha tryptasemia is quickly evolving. Epidemiology, pathophysiology, and strategies to identify and diagnose are discussed. Evidence-based management in the emergency setting and beyond is also explored and summarized. Key differences are described between these events and allergic reactions.


Assuntos
Angioedema/diagnóstico , Hipersensibilidade/diagnóstico , Toxinas Marinhas/biossíntese , Angioedema/fisiopatologia , Mimetismo Biológico , Humanos , Hipersensibilidade/fisiopatologia , Toxinas Marinhas/metabolismo , Triptases/análise , Triptases/deficiência
3.
Laeknabladid ; 107(10): 470-475, 2021 10.
Artigo em Islandês | MEDLINE | ID: mdl-34585673

RESUMO

Background Diagnosing anaphylaxis is often straightforward but can be challenging if the presentation is atypical. In patients with atypical symptoms suspected to be due to an acute allergic reaction, s-tryptase can give additional diagnostic information. Measuring s-tryptase is also helpful in diagnosing mastocytosis. Obtaining s-tryptase levels has been done in the emergency department (ED) at Landspitali since 2011. The aim of this study was to evaluate the benefit of obtaining s-tryptase levels in the ED. Methods With institutional review board approval, all cases where s-tryptase level was obtained in ED patients from 2011-2018 were retrospectively reviewed. A database was collected including information on patient demographics, presenting symptoms, treatment, diagnosis, s-tryptase level and follow up. Results A total of 214 patients had a s-tryptase level measured. Serum tryptase was elevated (>12 µg/L) in 36 cases. Females were 131 and average age 40.6 years. Of the patients, 86.4% had skin or mucosal symptoms, 48.1% cardiovascular symptoms, 49.5% respiratory symptoms and 36.0% had gastrointestinal symptoms. An allergist reviewed 126 returning patients and 65 were considered to have had an episode of anaphylaxis. Of those 65 were 4 patients which did not meet the diagnostic criteria for anaphylaxis but had raised s-tryptase levels. Sensitivity of s-tryptase measurement was 40.9% and specificity 97.1%. Conclusions Obtaining a s-tryptase level from ED patients with possible anaphylaxis seems to be useful in atypical cases. The measurement is specific but not sensitive. No cases of mastocytosis were identified in the patient cohort.


Assuntos
Anafilaxia , Adulto , Anafilaxia/diagnóstico , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Estudos Retrospectivos , Triptases
6.
Int Arch Allergy Immunol ; 182(11): 1135-1142, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34455412

RESUMO

INTRODUCTION: Mast cells and their major protein, the serine proteinase tryptase, can be involved in cutaneous photodamage and carcinogenesis. The serum test of tryptase (S-tryptase) measures total tryptase protein (active tryptase and inactive protryptases), and S-tryptase is elevated in a variety of diseases, for example, in mastocytosis and α-tryptasemia. OBJECTIVES: The objective of this study is to study whether S-tryptase is a marker of cutaneous photodamage and carcinogenesis. METHODS: Adult subjects (n = 399, aged 21-79) evaluated to be at risk for skin cancers were recruited at the dermatological policlinic and examined for photodamage severity, mole count, actinic keratoses (AKs), skin cancers, and immunosuppression (IS). A blood sample was analyzed for S-tryptase using the ImmunoCAP® Tryptase fluoroenzymeimmunoassay. RESULTS: There was no difference in S-tryptase between non-IS (n = 321) and IS (n = 78) subjects or between genders. S-tryptase correlated slightly to photodamage and AKs in 321 non-IS subjects, and this association can be related, in part, to the age of subjects. In 34 subjects, S-tryptase was elevated (≥13.5 ng/mL), and in 20 males, but not in 14 females, the photodamage level was significantly (p = 0.031) more severe than in 179 males with normal S-tryptase. In contrast, there were more frequently subjects (n = 12) with past or present skin cancer (basal or squamous cell carcinoma or melanoma) in 14 females with elevated S-tryptase than in 186 female controls. So far, no explanation has been found for the elevated S-tryptase. CONCLUSION: There are significant associations between elevated S-tryptase and skin carcinogenesis, but the molecular mechanisms are unclear and gender differences can exist.


Assuntos
Ceratose Actínica/sangue , Nevo/sangue , Envelhecimento da Pele , Neoplasias Cutâneas/sangue , Triptases/sangue , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Síndromes de Imunodeficiência/sangue , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Biomed Res Int ; 2021: 5521564, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34212030

RESUMO

Background: Cardiovascular disease (CVD) contributes critically to the mortality, morbidity, and economic problem of illness globally. Exercise is a share of everyone's life. Some evidence-based studies have frequently shown a progressive correlation between physical activity and good health. Objective: The effects of daily exercise on cardiomyocyte size, collagen content (fibrosis), and releasing mast cells (MCs') tryptase of the model of myocardial infarction (MI) were assessed. Methods: 40 rats were coincidentally spread into sham+inertia (control), sham+exercise, infarction+inertia, and infarction+exercise groups. An experimental model of acute MI was induced in infarction groups. One week after surgery, exercising groups were allowed to an aerobic exercise program for six weeks. At the endpoint of the study, all examinations were performed. Results: We found lesser fibrosis in sham+exercise and infarction+exercise groups compared to sham+inertia and infarction+inertia groups, respectively (p = 0.023, p = 0.001). Also, infarction groups were significantly lower than sham groups (p < 0.05) and the infarction+exercise group was significantly lower than the infarction+inertia group (p < 0.05). The effect of exercise on MCs while increased MC density and degranulation occur at the site of fibrosis, we demonstrated that exercise decreases both total MC density and degranulation in both sham and infarction groups (p < 0.05). Immunohistochemistry examinations were significantly higher expression of MCs' tryptase in infarction groups than sham groups (p < 0.05, p < 0.0001). Conclusion: Exercise improves fibrosis and cardiac function in both healthy and MI rats by inhibiting released MCs' tryptase.


Assuntos
Mastócitos/metabolismo , Mastócitos/fisiologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Condicionamento Físico Animal/fisiologia , Regeneração/fisiologia , Triptases/metabolismo , Animais , Ecocardiografia/métodos , Terapia por Exercício/métodos , Fibrose/metabolismo , Fibrose/fisiopatologia , Masculino , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/fisiologia , Ratos , Ratos Wistar , Função Ventricular Esquerda/fisiologia
10.
Ann Allergy Asthma Immunol ; 127(4): 427-434, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34298172

RESUMO

OBJECTIVE: Mast cell (MC) activation (MCA) defines the mechanism by which certain patients have symptoms owing to the effect of a wide range of mediators released from MCs upon their activation, when triggered by different stimuli. When these symptoms are severe and recurrent, the diagnosis of MCA syndrome (MCAS) might be considered. Here, we review the relevant aspects related to the pathogenesis of MCAS, with special emphasis on the prevalence and diagnostic relevance of KIT mutations. DATA SOURCES: PubMed was searched between 1980 and 2021 using the following terms: mast cell activation syndromes, mast cell activation, anaphylaxis, KIT mutations, KIT D816V, indolent systemic mastocytosis, bone marrow mastocytosis, cutaneous mastocytosis, IgE anaphylaxis, and idiopathic anaphylaxis. STUDY SELECTIONS: Only articles published in English were selected based on their relevance to MCAS or severe and recurrent anaphylaxis. RESULTS: MCAS can be classified as clonal MCAS and nonclonal MCAS depending on the presence vs absence of an underlying KIT mutation (mostly KIT D816V), respectively. In contrast to clonal MCAS in which MCA is associated with a primary MC disorder (ie, primary MCAS) such as mastocytosis or monoclonal MCAS, nonclonal MCAS can be secondary to known or unidentified triggers (ie, secondary and idiopathic MCAS, respectively). CONCLUSION: The clinical heterogeneity and complexity of the molecular assays needed for the study of patients with MCAS might lead to misdiagnosis, particularly when patients are evaluated at nonspecialized centers. Thus, referral of patients having clinical manifestations suggestive of MCAS to reference centers on mastocytosis and MC diseases is strongly recommended.


Assuntos
Mediadores da Inflamação/metabolismo , Mastócitos/imunologia , Mastocitose Sistêmica/genética , Mastocitose Sistêmica/patologia , Proteínas Proto-Oncogênicas c-kit/genética , Triptases/genética , Anafilaxia/patologia , Mutação da Fase de Leitura/genética , Humanos , Mastocitose Sistêmica/imunologia , Mutação Puntual/genética , Domínios Proteicos/genética
12.
Clin Ter ; 172(4): 369-371, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34247221

RESUMO

Abstract: Anaphylaxis is defined as a rapid systemic reaction that develops in individuals previously exposed to specific allergens. The new exposure causes systemic cellular degranulation, which in turn leads to cardiovascular and respiratory changes that are fatal if not treated immediately. One of the main problems of this scenario in the forensic field is the determination of a correct post-mortem diagnosis. Traditional methods, such as histopathological examination of the respiratory tract and the use of specific antibodies used in immunohistochemistry, are sensitive but not always specific and therefore do not guarantee a high degree of probability in the diagnosis of anaphylaxis. For this reason, a new and promising research frontier in this field of forensic pathology could be represented by the application of miRNAs as biomarkers, as has been done in other areas of medicine.


Assuntos
Anafilaxia/diagnóstico , Anafilaxia/mortalidade , Anafilaxia/fisiopatologia , Autopsia/métodos , Causas de Morte , Patologia Legal/métodos , Biomarcadores/análise , Humanos , Triptases/análise
14.
Ann Allergy Asthma Immunol ; 127(4): 420-426, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34175497

RESUMO

OBJECTIVE: To aid the clinician in correctly interpreting serum tryptase levels. DATA SOURCES: Primary peer-reviewed literature. STUDY SELECTIONS: Clinical and basic science peer-reviewed studies characterizing the genetic and physiological bases for tryptase generation, secretion, and elevation, including those describing serum tryptase levels in population-based cohort studies. RESULTS: Clinically measured basal serum tryptase (BST) consists of ostensibly inactive alpha- and beta-tryptase precursors. The autosomal dominant genetic trait hereditary alpha-tryptasemia is the most often cause for elevated BST levels, with other acquired causes, such as renal failure and clonal myeloid diseases being far less common. Acute increases in serum tryptase levels resulting from release of mature tryptase from secretory granules is specific to mast cell degranulation but is not detected in all cases of systemic anaphylaxis. CONCLUSION: Understanding the differences and distinguishing between acute increases in serum tryptase and chronic elevations in BST owing to inherited or acquired conditions is critical in the correct interpretation of this useful clinical biomarker.


Assuntos
Precursores Enzimáticos/sangue , Mastócitos/imunologia , Mastocitose/imunologia , Triptases/sangue , Anafilaxia/imunologia , Biomarcadores/sangue , Degranulação Celular/fisiologia , Humanos , Mastocitose/genética , Insuficiência Renal/sangue , Insuficiência Renal/patologia
15.
Int J Mol Sci ; 22(10)2021 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-34065716

RESUMO

Chronic respiratory diseases are often characterized by impaired epithelial function and remodeling. Mast cells (MCs) are known to home into the epithelium in respiratory diseases, but the MC-epithelial interactions remain less understood. Therefore, this study aimed to investigate the effect of MC proteases on bronchial epithelial morphology and function. Bronchial epithelial cells were stimulated with MC tryptase and/or chymase. Morphology and epithelial function were performed using cell tracking analysis and holographic live-cell imaging. Samples were also analyzed for motility-associated gene expression. Immunocytochemistry was performed to compare cytoskeletal arrangement. Stimulated cells showed strong alterations on gene, protein and functional levels in several parameters important for maintaining epithelial function. The most significant increases were found in cell motility, cellular speed and cell elongation compared to non-stimulated cells. Also, cell morphology was significantly altered in chymase treated compared to non-stimulated cells. In the current study, we show that MC proteases can induce cell migration and morphological and proliferative alterations in epithelial cells. Thus, our data imply that MC release of proteases may play a critical role in airway epithelial remodeling and disruption of epithelial function.


Assuntos
Brônquios/citologia , Brônquios/metabolismo , Quimases/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Mastócitos/enzimologia , Triptases/metabolismo , Divisão Celular , Linhagem Celular , Movimento Celular , Proliferação de Células , Citoesqueleto/metabolismo , Holografia , Humanos , Imageamento Tridimensional , Imuno-Histoquímica , Análise Serial de Tecidos
16.
Braz Oral Res ; 35: e061, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076187

RESUMO

Inflammatory periapical lesions are characterized by infiltration of different immune cell types, the functions of which depend on an effective vascular network. This study aimed to evaluate the mast cells density (MCD) in inflamatory odontogenic cysts capsules concerning microvascular density (MVD), microvascular area (MVA), and microvascular perimeter (MVP), and correlate such findings with the type of lesion, intensity of the inflammatory infiltrate, and thickness of the epithelial lining. Twenty inflamatory dentigerous cysts (IDCs), twenty radicular cysts (RCs), and twenty residual radicular cysts (RRCs) were submitted to immunohistochemical analysis using anti-tryptase and anti-CD34 antibodies. RCs exhibited the highest MCD, MVD, MVA, and MVP indexes (p = < 0.001, p = 0.008, p = 0.003 and p = < 0.001, respectively), and lesions with inflammatory infiltrate grade III showed the highest MVD (p = 0.044). Considering epithelial thickness, a higher MVP index was identified in lesions with hyperplastic epithelium (p = 0.018). In IDCs, RCs, and RRCs, a strong positive correlation was observed between MVA and MVP (r = 0.950 and p = < 0.001; r = 0.914 and p = < 0.001; r = 0.713 and p = < 0.001, respectively). In IDCs, a moderate correlation was observed between MCD and both MVA and MVP (r = 0.660 and p = 0.002; r = 0.634 and p = 0.003, respectively). These results suggest that tryptase-positive mast cells might play an important role in the angiogenic activity of IDCs, while RCs had the highest indexes. Our findings also confirmed that the intensity of the inflammatory infiltrate and epithelial thickness influence angiogenesis.


Assuntos
Cistos Odontogênicos , Cisto Radicular , Epitélio , Humanos , Mastócitos , Triptases
17.
J Allergy Clin Immunol Pract ; 9(8): 3166-3175.e2, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33965596

RESUMO

BACKGROUND: Mastocytosis comprises a heterogeneous group of disorders characterized by an accumulation of mast cells in 1 or more organs. Symptoms range from mild complaints to severe and life-threatening events. Impact on quality of life seems to vary widely, but influencing factors are poorly understood so far. OBJECTIVE: To examine impairments, psychological burden, health-related quality of life (HRQOL), and possible influencing factors in patients with mastocytosis. METHODS: In semistructured telephone interviews, patients provided information on impairments in everyday life and psychological burden caused by mastocytosis. HRQOL was measured using the Mastocytosis Quality of Life (MC-QoL) questionnaire. Clinical data were collected from patient files. RESULTS: A total of 101 adult patients with mastocytosis (74.3% women; mean age, 47.7 ± 13.5 years) were included. Half of the interviewed patients (50.6%) reported disease-related impairments in everyday life, and 42.4% stated a psychological burden. MC-QoL questionnaire scores showed a broad distribution, with a mean total score at a "mild" impairment level (mean total score, 34.7 ± 22.5). One-third of patients felt moderately (22.8%) or severely (13.9%) impaired, whereas one-third reported no impairment at all (30.7%). Symptoms of mast cell activation and perceived food intolerance had the highest impact on HRQOL. Higher age, higher body mass index, higher tryptase level, and longer duration of symptoms, as well as current drug therapy and pathological bone density, were each associated with reduced HRQOL. CONCLUSIONS: A high level of suffering and strong associations between impairments and symptom-related factors indicate the importance of addressing patients' concerns and adequate symptom management in mastocytosis.


Assuntos
Mastocitose , Qualidade de Vida , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Mastocitose/epidemiologia , Pessoa de Meia-Idade , Inquéritos e Questionários , Triptases
18.
Sci Rep ; 11(1): 10687, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34021178

RESUMO

Tuberculosis (TB) is still a major worldwide health threat and primarily a lung disease. The innate immune response against Mycobacterium tuberculosis (Mtb) is orchestrated by dendritic cells, macrophages, neutrophils, natural killer cells and apparently mast cells (MCs). MCs are located at mucosal sites including the lungs and contribute in host-defence against pathogens, but little is known about their role during Mtb infection. This study investigates the location and characteristics of MCs in TB lesions to assess their contribution to TB pathology. To this purpose, number, location and phenotype of MCs was studied in 11 necropsies of pulmonary TB and 3 necropsies of non-TB infected lungs that were used as controls. MCs were localised at pneumonic areas, in the granuloma periphery and particularly abundant in fibrotic tissue. Furthermore, MCs displayed intracellular Mtb and IL-17A and TGF-ß immunostaining. These findings were validated by analysing, post-mortem lung tissue microarrays from 44 individuals with pulmonary TB and 25 control subjects. In affected lungs, increased numbers of MCs expressing intracellularly both tryptase and chymase were found at fibrotic sites. Altogether, our data suggest that MCs are recruited at the inflammatory site and that actively produce immune mediators such as proteases and TGF-ß that may be contributing to late fibrosis in TB lesions.


Assuntos
Contagem de Leucócitos , Mastócitos/imunologia , Mastócitos/metabolismo , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Antígenos de Bactérias/imunologia , Fibrose , Granuloma do Sistema Respiratório/patologia , Humanos , Imuno-Histoquímica , Triptases/metabolismo
19.
Curr Allergy Asthma Rep ; 21(5): 33, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33970354

RESUMO

PURPOSE OF REVIEW: Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait and a common cause of elevated basal serum tryptase in Western populations. It is a risk factor for severe anaphylaxis among individuals with venom allergy and an established modifier of anaphylaxis and mast cell mediator-associated symptoms among patients with systemic mastocytosis. Understanding the physiology of tryptases and how this may relate to the clinical features associated with HαT is the first step in identifying optimal medical management and targets for novel therapeutics. RECENT FINDINGS: HαT prevalence is increased in both clonal and non-clonal mast cell-associated disorders where it augments symptoms of immediate hypersensitivity, including anaphylaxis. The unique properties of naturally occurring α/ß-tryptase heterotetramers may explain certain elements of phenotypes associated with HαT, though additional mechanisms are being evaluated. This review provides an overview of the clinical and translational studies that have identified HαT as a modifier of mast cell-associated disorders and anaphylaxis and discusses mechanisms that may potentially explain some of these clinical findings.


Assuntos
Anafilaxia , Mastocitose , Triptases , Anafilaxia/sangue , Anafilaxia/genética , Anafilaxia/imunologia , Genótipo , Humanos , Mastócitos/imunologia , Mastocitose/sangue , Mastocitose/genética , Mastocitose/imunologia , Fenótipo , Triptases/sangue , Triptases/genética , Triptases/imunologia
20.
Allergol Immunopathol (Madr) ; 49(3): 91-99, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33938193

RESUMO

INTRODUCTION AND OBJECTIVES: There are a few reports in the literature about the successful use of sugammadex in the treatment of hypersensitivity reactions caused by rocuronium; however, the pathophysiological mechanism is still unknown. This study aims to investigate the changes caused by rocuronium in the lung and the effect of sugammadex on these changes with biochemical, light microscopic and immunohistochemical parameters on a rat model. MATERIALS AND METHODS: For the study, 28-male Sprague-Dawley rats were randomly divided, seven of each, into four groups. Group C (control) received only 0. 9 % NaCl without any drug. Group R received rocuronium alone 1mg/kg. Group S received sugammadex alone 96 mg/kg. Group RS received rocuronium 1mg/kg and sugammadex 96 mg/kg. After 24 h later, the animals were sacrificed and their tissues were removed. Biochemical (IgE/CRP), light microscopic and immunohistochemical findings were recorded. RESULTS: Immunoglobulin E and CRP levels, peribronchial, alveolar septal lymphocytic infiltration, thickening of the alveolar membranes and bleeding sites in Group R were significantly higher than all the other groups. In Group RS, while these parameters were significantly lower than that of Group R and Group S, it was significantly higher than that of Group C. Total mast cells and tryptase-positive mast cells counts were significantly higher in Group R than in all other groups. In Group RS, these parameters were statistically lower than that of Group R and Group S, but higher than that of Group C. CONCLUSIONS: This study shows that allergic inflammatory changes due to rocuronium in the lungs of rats are reduced with sugammadex. These results support cases of anaphylaxis due to rocuronium which improved with sugammadex.


Assuntos
Hipersensibilidade/complicações , Inflamação/prevenção & controle , Pulmão/efeitos dos fármacos , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Rocurônio/efeitos adversos , Sugammadex/farmacologia , Anafilaxia/induzido quimicamente , Anafilaxia/prevenção & controle , Animais , Proteína C-Reativa/análise , Modelos Animais de Doenças , Hemorragia/induzido quimicamente , Imunoglobulina E/análise , Inflamação/induzido quimicamente , Inflamação/imunologia , Linfócitos , Masculino , Mastócitos/citologia , Mastócitos/enzimologia , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Rocurônio/antagonistas & inibidores , Triptases/análise
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