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1.
J Allergy Clin Immunol ; 153(4): 1050-1062.e6, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38135009

RESUMO

BACKGROUND: Alpha-gal (Galα1-3Galß1-4GlcNAc) is a carbohydrate with the potential to elicit fatal allergic reactions to mammalian meat and drugs of mammalian origin. This type of allergy is induced by tick bites, and therapeutic options for this skin-driven food allergy are limited to the avoidance of the allergen and treatment of symptoms. Thus, a better understanding of the immune mechanisms resulting in sensitization through the skin is crucial, especially in the case of a carbohydrate allergen for which underlying immune responses are poorly understood. OBJECTIVE: We aimed to establish a mouse model of alpha-gal allergy for in-depth immunologic analyses. METHODS: Alpha-galactosyltransferase 1-deficient mice devoid of alpha-gal glycosylations were sensitized with the alpha-gal-carrying self-protein mouse serum albumin by repetitive intracutaneous injections in combination with the adjuvant aluminum hydroxide. The role of basophils and IL-4 in sensitization was investigated by antibody-mediated depletion. RESULTS: Alpha-gal-sensitized mice displayed increased levels of alpha-gal-specific IgE and IgG1 and developed systemic anaphylaxis on challenge with both alpha-gal-containing glycoproteins and glycolipids. In accordance with alpha-gal-allergic patients, we detected elevated numbers of basophils at the site of sensitization as well as increased numbers of alpha-gal-specific B cells, germinal center B cells, and B cells of IgE and IgG1 isotypes in skin-draining lymph nodes. By depleting IL-4 during sensitization, we demonstrated for the first time that sensitization and elicitation of allergy to alpha-gal and correspondingly to a carbohydrate allergen is dependent on IL-4. CONCLUSION: These findings establish IL-4 as a potential target to interfere with alpha-gal allergy elicited by tick bites.


Assuntos
Anafilaxia , Hipersensibilidade Alimentar , Picadas de Carrapatos , Animais , Humanos , Camundongos , Alérgenos , Imunoglobulina E , Imunoglobulina G , Interleucina-4 , Mamíferos
2.
Chimia (Aarau) ; 78(5): 326-332, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38822776

RESUMO

Electron paramagnetic resonance (EPR) spectroscopy is a powerful tool for in situ/operando tracking of catalytic reactions that involve paramagnetic species either as a catalyst (e.g. transition metal ions or defects), reaction intermediates (radicals) or poisoning agents such as coke. This article provides a summary of recent experimental examples and developments in resonator design as well as detection schemes that were carried out in our group. Opportunities for applying this technique are illustrated by examples, including studies of transition metal exchanged zeolites and metal-free zeolites as well as metal oxide catalysts. The inherent limitations of EPR applied at high temperatures are discussed, as well as strategies in reducing or lifting these restrictions are evaluated and ideas for future improvements and methodologies are discussed.

3.
Chimia (Aarau) ; 78(6): 427-430, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38946416

RESUMO

EquipSent is a volunteer-based non-profit organization aiming at creating conditions for sustainable teaching, study, and academic research worldwide. Used, functional equipment is collected by its members, who are responsible for matching the donations with the receivers in need. After starting in 2017, nine big transfers were accomplished that significantly impacted the quality of local scientific and educational life. In this article, we show how EquipSent as an organization strives to align with the Sustainable Development Goals (SDG) in Chemistry in Switzerland.

4.
Proc Natl Acad Sci U S A ; 117(20): 10983-10988, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32366650

RESUMO

Allergies are highly prevalent, and allergic responses can be triggered even in the absence of allergens due to Pavlovian conditioning to a specific cue. Here we show in humans suffering from allergic rhinitis that merely reencountering the environmental context in which an allergen was administered a week earlier is sufficient to trigger an allergic response-but only if participants had slept after allergen exposure. This context-conditioning effect was entirely absent when participants stayed awake the night after allergen exposure or were tested in a different context. Unlike in context conditioning, cue conditioning (to an odor stimulus) occurred independently of sleep, a differential pattern that is likewise observed for conditioning in the behavioral domain. Our findings provide evidence that allergic responses can be conditioned to contextual information alone, even after only a single-trial conditioning procedure, and that sleep is necessary to consolidate this rapidly acquired maladaptive response. The results unravel a mechanism that could explain part of the strong psychological impact on allergic responses.


Assuntos
Alérgenos/imunologia , Rinite Alérgica/imunologia , Sono/imunologia , Sono/fisiologia , Adulto , Condicionamento Clássico/fisiologia , Feminino , Humanos , Aprendizagem/fisiologia , Masculino , Propilenoglicol , Vigília , Adulto Jovem
5.
J Allergy Clin Immunol ; 150(2): 396-405.e11, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35459547

RESUMO

BACKGROUND: The α-Gal syndrome is associated with the presence of IgE directed to the carbohydrate galactose-α-1,3-galactose (α-Gal) and is characterized by a delayed allergic reaction occurring 2 to 6 hours after ingestion of mammalian meat. On the basis of their slow digestion and processing kinetics, α-Gal-carrying glycolipids have been proposed as the main trigger of the delayed reaction. OBJECTIVE: We analyzed and compared the in vitro allergenicity of α-Gal-carrying glycoproteins and glycolipids from natural food sources. METHODS: Proteins and lipids were extracted from pork kidney (PK), beef, and chicken. Glycolipids were purified from rabbit erythrocytes. The presence of α-Gal and IgE binding of α-Gal-allergic patient sera (n = 39) was assessed by thin-layer chromatography as well as by direct and inhibition enzyme-linked immunosorbent assay. The in vitro allergenicity of glycoproteins and glycolipids from different meat extracts was determined by basophil activation test. Glycoprotein stability was evaluated by simulated gastric and intestinal digestion assays. RESULTS: α-Gal was detected on glycolipids of PK and beef. Patient IgE antibodies recognized α-Gal bound to glycoproteins and glycolipids, although binding to glycoproteins was more potent. Rabbit glycolipids were able to strongly activate patient basophils, whereas lipid extracts from PK and beef were also found to trigger basophil activation, but at a lower capacity compared to the respective protein extracts. Simulated gastric digestion assays of PK showed a high stability of α-Gal-carrying proteins in PK. CONCLUSION: Both α-Gal-carrying glycoproteins and glycolipids are able to strongly activate patient basophils. In PK and beef, α-Gal epitopes seem to be less abundant on glycolipids than on glycoproteins, suggesting a major role of glycoproteins in delayed anaphylaxis upon consumption of these food sources.


Assuntos
Hipersensibilidade Alimentar , Galactose , Alérgenos , Animais , Bovinos , Glicolipídeos , Glicoproteínas , Imunidade , Imunoglobulina E , Mamíferos , Carne , Coelhos
6.
J Environ Manage ; 325(Pt B): 116487, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36419305

RESUMO

The Agenda 2030 of the United Nations stipulates an ambitious set of 17 Sustainable Development Goals (SDGs). They were globally agreed upon and demand coherent, context-specific implementation at the national level. To address the complexity of challenges therein, the Agenda is designed to be integrated, indivisible, and universal. The numerous multifaceted interactions in-between the SDGs and with corresponding measures pose a complex challenge for decision-makers implementing them worldwide that requires support for a comprehensive discourse in the science-society-policy arena. Research on the interactions between the SDGs has been flourishing and can help to understand where policy options might be most successfully located. A catalytic effect on several other goals is, e.g., often attributed to SDG 6 on water and sanitation. However, beyond the where to locate policy options, it is similarly important to understand how potential policy options would affect the SDGs and their targets. We developed eleven options and 85 measures as context-specific pathways to advance the SDG 6 Targets in Austria. As a country in the Global North and with a generally far-established water and sanitation infrastructure and management, this responds to the Agenda's demand for universal applicability and can serve as an example to illustrate potential challenges beyond basic infrastructure provision and management. The proposed options cover resources-oriented sanitation, blue-green-brown infrastructure, efficient use and integrated management of water resources, maintenance and restoration of ecological functions of inland waters, reduction of diffuse discharge of nutrients and problematic substances as well as trace substances, water, sanitation and hygiene in public spaces, groundwater protection, development cooperation as well as co-design and co-creation. Their effects on the SDG 6 Targets are evaluated using a 7-point-scale. The evaluation method is simple and practicable, and fosters discourse on the entire water cycle amongst the expert group applying the method. The evaluated effects on the targets are found to be unanimously positive or neutral, but trade-offs might arise when including other SDGs in the assessment, making an expansion of the evaluation necessary for coherent implementation. The results can be used as a baseline to support follow-up discussions with stakeholders and decision-makers.


Assuntos
Saneamento , Desenvolvimento Sustentável , Áustria , Higiene , Água
7.
Angew Chem Int Ed Engl ; 62(34): e202303574, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37292054

RESUMO

Cu-exchanged mordenite (MOR) is a promising material for partial CH4 oxidation. The structural diversity of Cu species within MOR makes it difficult to identify the active Cu sites and to determine their redox and kinetic properties. In this study, the Cu speciation in Cu-MOR materials with different Cu loadings has been determined using operando electron paramagnetic resonance (EPR) and operando ultraviolet-visible (UV/Vis) spectroscopy as well as in situ photoluminescence (PL) and Fourier-transform infrared (FTIR) spectroscopy. A novel pathway for CH4 oxidation involving paired [CuOH]+ and bare Cu2+ species has been identified. The reduction of bare Cu2+ ions facilitated by adjacent [CuOH]+ demonstrates that the frequently reported assumption of redox-inert Cu2+ centers does not generally apply. The measured site-specific reaction kinetics show that dimeric Cu species exhibit a faster reaction rate and a higher apparent activation energy than monomeric Cu2+ active sites highlighting their difference in the CH4 oxidation potential.

8.
J Am Chem Soc ; 144(29): 13384-13393, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35834364

RESUMO

The increasing demand for short chain olefins like propene for plastics production and the availability of shale gas make the development of highly performing propane dehydrogenation (PDH) catalysts, robust toward industrially applied harsh regeneration conditions, a highly important field of research. A combination of surface organometallic chemistry and thermolytic molecular precursor approach was used to prepare a nanometric, bimetallic Pt-Mn material (3 wt % Pt, 1.3 wt % Mn) supported on silica via consecutive grafting of a Mn and Pt precursor on surface OH groups present on the support surface, followed by a treatment under a H2 flow at high temperature. The material exhibits a 70% fraction of the overall Mn as MnII single sites on the support surface; the remaining Mn is incorporated in segregated Pt2Mn nanoparticles. The material shows great performance in PDH reaction with a low deactivation rate. In particular, it shows outstanding robustness during repeated regeneration cycles, with conversion and selectivity stabilizing at ca. 37 and 98%, respectively. Notably, a material with a lower Pt loading of only 0.05 wt % shows an outstanding catalytic performance─initial productivity of 4523 gC3H6/gPt h and an extremely low kd of 0.003 h-1 under a partial pressure of H2, which are among the highest reported productivities. A combined in situ X-ray absorption spectroscopy, scanning transmission electron microscopy, electron paramagnetic resonance, and metadynamics at the density functional theory level study could show that the strong interaction between the MnII-decorated support and the unexpectedly segregated Pt2Mn particles is most likely responsible for the outstanding performance of the investigated materials.

9.
Allergy ; 77(10): 2924-2936, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35266570

RESUMO

The worldwide use of COVID-19 vaccines has shown that immediate allergic reactions to the ingredients are rare but should be clarified by means of an allergological work-up. This review aims to highlight the current state of knowledge and possible pathogenesis based on the literature published to date. In addition to recording a detailed history and performing skin tests, cellular tests (basophil activation or basophil histamine release test) by using the vaccines or modified compounds containing polyethylene glycol (PEG), rather than unmodified PEGs, have proven to be particularly helpful. Negative results with vaccines seem to indicate tolerance. Details of the performance of these cellular tests with different vaccines, PEGs of different molecular weights, other ingredients of the vaccines, as well as other PEGylated drugs, and the results in the context of COVID-19 vaccination of various working groups worldwide are summarized.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Hipersensibilidade , Teste de Degranulação de Basófilos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Polietilenoglicóis
10.
Allergy ; 77(7): 2200-2210, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34806775

RESUMO

BACKGROUND: Polyethylene glycol (PEG) may elicit anaphylaxis to COVID-19 mRNA vaccines, and guidance for patients at risk is needed. METHODS: In retrospective patients with PEG allergy collected from 2006 till 2019, clinical, skin, and basophil activation test (BAT) characteristics discriminative for PEG allergy were analyzed and compared with the literature. In 421 prospective real-life patients asking for allergy workup for COVID-19 vaccine hypersensitivity in 2020/2021, risk assessment was performed and tolerance of the recommended vaccination approach was assessed. RESULTS: Ten patients with PEG allergy were found in the retrospective cohort. Patients reacted with immediate anaphylaxis (100%) not only to PEG-based laxatives/bowel preparations or injections, but also to cold medication, antiseptics, analgetics, or antibiotics. Skin tests ± BAT with PEG ± elicitors were positive in 10/10. Provocation tests were positive in 7/9 patients. From the prospective cohort, 370/421 patients self-reporting increased risk for vaccine allergy lacked criteria necessitating allergy workup and were recommended for routine vaccination. A total of 51/421 patients were tested, and three (6%) with PEG allergy were identified, whereas 48 patients remained negative in skin tests. Vaccination was recommended in all those patients. No hypersensitivity reactions were reported to vaccination including six PEG-allergic patients tolerating COVID-19 vaccination. CONCLUSIONS: Taking a detailed history excluded PEG allergy in most referred patients and enabled direct safe vaccination. Immediate urticaria/anaphylaxis to typical elicitors identified patients requiring PEG allergy workup. Skin tests ± BAT identified PEG allergy and helped to select the vaccine and the vaccination approach. Even PEG-allergic patients can tolerate COVID-19 vaccines.


Assuntos
Anafilaxia , Vacinas contra COVID-19 , COVID-19 , Polietilenoglicóis , Anafilaxia/etiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Polietilenoglicóis/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos , Gestão de Riscos
11.
Anal Bioanal Chem ; 413(4): 1091-1098, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33244685

RESUMO

Recycling will be of increasing importance in the future, especially for plastic packaging waste mainly consisting of polyolefins. One major problem of recyclates comprises impurities which can have a significant negative impact on future product properties. Polyamide 6 can be found widely as contaminant in recycled polyolefins, leading to a need of quantification methods thereof. In this paper, a method development for the quantitative analysis of polyamide 6 is presented based on analysing ε-caprolactam and related cyclic oligomers as marker compounds in model recyclates of high- and low-density polyethylene and polypropylene compounded with low amounts of polyamide 6. For the method development and tentative identification of the different cyclic compounds, a HPLC-QTOF-MS was used and it was possible to detect six different compounds, ε-caprolactam and the corresponding cyclic di- to hexamer. The quantification was performed with a HPLC-QQQ-MS, equipped with a HILIC column, after sample preparation via microwave-assisted extraction. It could be shown that a good linearity from 0.2 up to 5 wt% polyamide 6 in the different polyolefins can be achieved. The cyclic trimer and tetramer show a low limit of quantification and are therefore well-suited for the quantification, whereas the other cyclic compounds can be then used as qualifiers to avoid false positives. To guarantee the applicability of the method, six real recyclate materials were analysed, whereby in three of them low amounts of polyamide 6 could be detected. Graphical abstract.

12.
Int Arch Allergy Immunol ; 181(2): 119-127, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31805569

RESUMO

BACKGROUND: Alpha-gal syndrome is a complex allergy with high clinical relevance regarding mammalian-derived food and drugs and is characterized by the presence of IgE antibodies directed at the carbohydrate galactose-α-1,3-galactose. As not all alpha-gal sIgE-positive individuals pre-sent clinical symptoms upon consumption of mammalian meat, the diagnostic value of alpha-gal sIgE has yet to be clarified. OBJECTIVE: To investigate the prevalence of alpha-gal-sIgE positivity among allergy patients, examine the impact of tick bites as associated risk factors and determine the diagnostic value of alpha-gal-sIgE positivity. METHODS: A retrospective cross-sectional study evaluating patients in the Allergy Unit was performed. Alpha-gal-sIgE levels were assessed by ImmunoCAP assay. Exposure to tick bites was assessed by a questionnaire. A receiver operating characteristics (ROC) curve analysis was performed to determine the diagnostic value of alpha-gal sIgE for the diagnosis of alpha-gal syndrome. RESULTS: In the study population (n = 1369), the overall prevalence of alpha-gal-sIgE-positive (≥0.10 kUA/L) individuals was 19.9%, and the highest prevalence (30.2%) was found in patients with insect venom allergies. A reported tick bite within the 12 months prior to blood sampling significantly increased the risk of alpha-gal-sIgE positivity (OR 2.084). The ROC curve analysis indicated alpha-gal sIgE ≥0.54 kUA/L as the optimal cutoff point for assessing the diagnostic value of alpha-gal syndrome in allergy patients. CONCLUSIONS: In allergy care settings, alpha-gal-sIgE positivity is a common finding. Alpha-gal sIgE is a sensitive marker in the diagnosis of alpha-gal syndrome but has limited predictive value for the characteristics or severity of this allergy.


Assuntos
Alérgenos/imunologia , Hipersensibilidade Alimentar/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Imunoglobulina E/imunologia , Lactente , Masculino , Carne , Pessoa de Meia-Idade , Prevalência , Curva ROC , Estudos Retrospectivos , Picadas de Carrapatos/imunologia , Carrapatos/imunologia , Adulto Jovem
13.
Int Arch Allergy Immunol ; 181(2): 111-118, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31794966

RESUMO

BACKGROUND: Venom immunotherapy (VIT) is an established and effective treatment for patients with Hymenoptera venom allergies. Especially during the build-up of VIT, systemic allergic reactions are a key issue. OBJECTIVE: To investigate the safety and effectiveness of a 3-day rush insect VIT protocol and a strategy for the management of individuals with VIT-induced anaphylaxis. METHODS: In this retrospective monocentric study, 11-year data regarding build-up cycles of VIT were retrieved from institutional records. The following parameters of VIT-induced anaphylaxis were analyzed: frequency, severity, time of occurrence within the build-up cycle, and impact on the success of VIT. The effectiveness of VIT was assessed by the results of sting challenges (SCs) by the culprit insect. RESULTS: In total, 1,317 initial build-up cycles of VIT were evaluated in this study, and the frequency of VIT-induced anaphylaxis was 6.6%. Anaphylaxis occurred most frequently when the daily cumulative venom dose was ≥100 µg. A group (n = 65) of patients with VIT-induced anaphylaxis in this dose range temporarily received a reduced maintenance dose, and without additional co-medications or complications, the target dose was reached after a second build-up in 91% of the cycles. After completing the VIT build-up, SCs were performed in 76.9% of the cohort, and the effectiveness of VIT was confirmed by 98.5% of the tests. CONCLUSIONS: In this study, we report a 3-day VIT rush protocol with a reasonable rate of VIT-induced anaphylaxis and excellent effectiveness of VIT.


Assuntos
Venenos de Artrópodes/efeitos adversos , Venenos de Artrópodes/imunologia , Imunoterapia/efeitos adversos , Mordeduras e Picadas de Insetos/imunologia , Insetos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alérgenos/imunologia , Anafilaxia/imunologia , Animais , Dessensibilização Imunológica/métodos , Feminino , Humanos , Fatores Imunológicos/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
14.
J Allergy Clin Immunol ; 143(1): 182-189, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30125663

RESUMO

BACKGROUND: Galactose-alpha-1,3-galactose (alpha-gal) syndrome is characterized by the presence of serum specific IgE antibodies to alpha-gal and delayed type I allergic reactions to the carbohydrate alpha-gal after consumption of mammalian (red) meat products and drugs of mammalian origin. Diagnostics currently rely on patient history, skin tests, determination of serum specific IgE antibodies, and oral food or drug challenges. OBJECTIVE: We sought to assess the utility of different basophil parameters (basophil reactivity and sensitivity, the ratio of the percentage of CD63+ basophils induced by the alpha-gal-containing allergen to the percentage of CD63+ basophils after stimulation with anti-FcεRI antibody [%CD63+/anti-FcεRI], and area under the dose-response curve [AUC]) as biomarkers for the clinical outcome of patients with alpha-gal syndrome compared with subjects with asymptomatic alpha-gal sensitization. METHODS: In addition to routine diagnostics, a basophil activation test (Flow CAST) with different concentrations of alpha-gal-containing allergens (eg, commercially available alpha-gal-carrying proteins and pork kidney extracts) was performed in 21 patients with alpha-gal syndrome, 12 alpha-gal-sensitized subjects, and 18 control subjects. RESULTS: Alpha-gal-containing allergens induced strong basophil activation in a dose-dependent manner in patients. Basophil reactivity at distinct allergen concentrations, the %CD63+/anti-FcεRI ratio across most allergen concentrations, the AUC of dose-response curves, and basophil allergen threshold sensitivity (CD-sens) with pork kidney extract were significantly higher in patients with alpha-gal syndrome compared with those in sensitized subjects. All parameters were negative in control subjects. CONCLUSION: The basophil activation test should be considered as an additional diagnostic test before performing time-consuming and potentially risky oral provocation tests. The %CD63+/anti-FcεRI ratio for all allergens and AUCs for pork kidney were the best parameters for distinguishing patients with alpha-gal syndrome from subjects with asymptomatic alpha-gal sensitization.


Assuntos
Anafilaxia , Basófilos/imunologia , Galactose/efeitos adversos , Imunoglobulina E/imunologia , Adulto , Anafilaxia/diagnóstico , Anafilaxia/imunologia , Anafilaxia/patologia , Basófilos/patologia , Feminino , Galactose/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Cutâneos , Síndrome
15.
Curr Allergy Asthma Rep ; 19(1): 3, 2019 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-30673913

RESUMO

PURPOSE OF REVIEW: The alpha-Gal (α-Gal) syndrome is characterized by the presence of IgE antibodies directed at the carbohydrate galactose-alpha-1,3-galactose (α-Gal). In this article, we review the presence of α-Gal in food and non-food sources; we discuss the evolutionary context of the antibody response to α-Gal and highlight immune responses to α-Gal and other carbohydrates. RECENT FINDINGS: IgE antibodies have been associated with delayed allergy to red meat. In addition to food, drugs, and other products of animal origin are increasingly perceived as a risk for patients sensitized to α-Gal. The link between tick bites and anti-α-Gal IgE-antibody production that has been established first by epidemiological studies has now been confirmed in mouse models. The anti-α-Gal immune response is complex and characterized by a unique feature. IgM and IgG antibodies have been found to confer protection against pathogens whereas the IgE-response to α-Gal is detrimental and causes severe reactions upon exposure to mammalian meat and other products.


Assuntos
Anafilaxia/imunologia , Hipersensibilidade Alimentar/imunologia , Galactose/efeitos adversos , Hipersensibilidade Tardia/imunologia , Carne Vermelha/efeitos adversos , Animais , Galactose/análogos & derivados , Humanos , Camundongos
16.
J Allergy Clin Immunol ; 139(4): 1311-1320, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27658762

RESUMO

BACKGROUND: Schnitzler syndrome is an adult-onset autoinflammatory disease characterized by urticarial exanthema and monoclonal gammopathy accompanied by systemic symptoms such as fever, bone, and muscle pain. Up to now, approved treatment options are not available. OBJECTIVE: We assessed effects of the anti-IL-1ß mAb canakinumab on the clinical signs and symptoms of Schnitzler syndrome. METHODS: In this phase II, randomized placebo-controlled multicenter study, 20 patients with active disease enrolled in 4 German study centers. Patients were randomly assigned to receive single subcutaneous canakinumab 150 mg or placebo injections for 7 days, followed by a 16-week open-label phase with canakinumab injections on confirmed relapse of symptoms. The primary end point was the proportion of patients with complete clinical response evaluated by physician global assessment at day 7. Key secondary end points included changes in patient-reported disease activity (Schnitzler activity score), inflammation markers (C-reactive protein and serum amyloid A), and quality-of-life assessments (Dermatology Life Quality Index and 36-item short form health survey). RESULTS: The proportion of patients with complete clinical response at day 7 was significantly higher (P = .001) in the canakinumab-treated group (n = 5 of 7) than in the placebo group (n = 0 of 13). Levels of inflammation markers C-reactive protein and serum amyloid A and quality-of-life scores were significantly reduced in canakinumab-treated but not in placebo-treated individuals. Positive effects continued up to 16 weeks. Adverse events were manageable and included respiratory tract infections, gastrointestinal symptoms, and hypertension. CONCLUSIONS: In this first placebo-controlled study, canakinumab was effective in patients with Schnitzler syndrome, and thus canakinumab may be further evaluated as a therapeutic option for this rare disease.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Síndrome de Schnitzler/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Proteína C-Reativa/análise , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Proteína Amiloide A Sérica/análise , Resultado do Tratamento
17.
Cereb Cortex ; 26(6): 2863-81, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26984895

RESUMO

How neuronal activity of motor cortex is related to movement is a central topic in motor neuroscience. Motor-cortical single neurons are more closely related to hand movement velocity than speed, that is, the magnitude of the (directional) velocity vector. Recently, there is also increasing interest in the representation of movement parameters in neuronal population activity, such as reflected in the intracranial EEG (iEEG). We show that in iEEG, contrasting to what has been previously found on the single neuron level, speed predominates over velocity. The predominant speed representation was present in nearly all iEEG signal features, up to the 600-1000 Hz range. Using a model of motor-cortical signals arising from neuronal populations with realistic single neuron tuning properties, we show how this reversal can be understood as a consequence of increasing population size. Our findings demonstrate that the information profile in large population signals may systematically differ from the single neuron level, a principle that may be helpful in the interpretation of neuronal population signals in general, including, for example, EEG and functional magnetic resonance imaging. Taking advantage of the robust speed population signal may help in developing brain-machine interfaces exploiting population signals.


Assuntos
Atividade Motora/fisiologia , Córtex Motor/fisiologia , Neurônios/fisiologia , Adolescente , Adulto , Braço/fisiologia , Fenômenos Biomecânicos , Eletrocorticografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Testes Neuropsicológicos , Adulto Jovem
18.
J Allergy Clin Immunol ; 138(6): 1663-1671.e9, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27372568

RESUMO

BACKGROUND: Component resolution recently identified distinct sensitization profiles in honey bee venom (HBV) allergy, some of which were dominated by specific IgE to Api m 3 and/or Api m 10, which have been reported to be underrepresented in therapeutic HBV preparations. OBJECTIVE: We performed a retrospective analysis of component-resolved sensitization profiles in HBV-allergic patients and association with treatment outcome. METHODS: HBV-allergic patients who had undergone controlled honey bee sting challenge after at least 6 months of HBV immunotherapy (n = 115) were included and classified as responder (n = 79) or treatment failure (n = 36) on the basis of absence or presence of systemic allergic reactions upon sting challenge. IgE reactivity to a panel of HBV allergens was analyzed in sera obtained before immunotherapy and before sting challenge. RESULTS: No differences were observed between responders and nonresponders regarding levels of IgE sensitization to Api m 1, Api m 2, Api m 3, and Api m 5. In contrast, Api m 10 specific IgE was moderately but significantly increased in nonresponders. Predominant Api m 10 sensitization (>50% of specific IgE to HBV) was the best discriminator (specificity, 95%; sensitivity, 25%) with an odds ratio of 8.444 (2.127-33.53; P = .0013) for treatment failure. Some but not all therapeutic HBV preparations displayed a lack of Api m 10, whereas Api m 1 and Api m 3 immunoreactivity was comparable to that of crude HBV. In line with this, significant Api m 10 sIgG4 induction was observed only in those patients who were treated with HBV in which Api m 10 was detectable. CONCLUSIONS: Component-resolved sensitization profiles in HBV allergy suggest predominant IgE sensitization to Api m 10 as a risk factor for treatment failure in HBV immunotherapy.


Assuntos
Alérgenos/uso terapêutico , Venenos de Abelha/uso terapêutico , Dessensibilização Imunológica/métodos , Hipersensibilidade/terapia , Adolescente , Adulto , Idoso , Alérgenos/imunologia , Venenos de Abelha/imunologia , Criança , Reações Cruzadas , Feminino , Humanos , Hipersensibilidade/imunologia , Imunização , Imunoglobulina E/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Adulto Jovem
20.
J Dtsch Dermatol Ges ; 14(1): 38-44, 2016 Jan.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-26713635

RESUMO

The development of component-resolved diagnostics instead of whole extracts has brought about major advances in recent years. Particularly remarkable has been the identification of new disease entities based on the detection of IgE antibodies against specific individual components. In this context, delayed immediate-type hypersensitivity to red meat and innards plays a key role. This disorder is more common in German-speaking countries and likely still underdiagnosed. Affected individuals exhibit delayed type I reactions following the consumption of red meat or innards (responses to the latter are more rapid). All patients have IgE antibodies against the oligosaccharide galactose-α-1,3-galactose - alpha-gal. Those affected also have to avoid alpha-gal-containing drugs such as cetuximab or gelatin-containing colloidal solutions. Also referred to as alpha-gal syndrome, this condition is unique in that it is characterized by type I hypersensitivity to a sugar instead of a protein. Given that many patients have a history of recurrent episodes of acute urticaria or angioedema, dermatologists should be familiar with the alpha-gal syndrome.


Assuntos
Dissacarídeos/efeitos adversos , Toxidermias/diagnóstico , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Imediata/diagnóstico , Carne/efeitos adversos , Toxidermias/imunologia , Hipersensibilidade Alimentar/imunologia , Humanos , Hipersensibilidade Imediata/etiologia , Hipersensibilidade Imediata/imunologia
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