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1.
Phys Chem Chem Phys ; 26(3): 2332-2340, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38165839

RESUMO

Oxide-derived metals are produced by reducing an oxide precursor. These materials, including gold, have shown improved catalytic performance over many native metals. The origin of this improvement for gold is not yet understood. In this study, operando non-resonant sum frequency generation (SFG) and ex situ high-pressure X-ray photoelectron spectroscopy (HP-XPS) have been employed to investigate electrochemically-formed oxide-derived gold (OD-Au) from polycrystalline gold surfaces. A range of different oxidizing conditions were used to form OD-Au in acidic aqueous medium (H3PO4, pH = 1). Our electrochemical data after OD-Au is generated suggest that the surface is metallic gold, however SFG signal variations indicate the presence of subsurface gold oxide remnants between the metallic gold surface layer and bulk gold. The HP-XPS results suggest that this subsurface gold oxide could be in the form of Au2O3 or Au(OH)3. Furthermore, the SFG measurements show that with reducing electrochemical treatments the original gold metallic state can be restored, meaning the subsurface gold oxide is released. This work demonstrates that remnants of gold oxide persist beneath the topmost gold layer when the OD-Au is created, potentially facilitating the understanding of the improved catalytic properties of OD-Au.

2.
J Phys Chem A ; 124(20): 3984-3992, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32242664

RESUMO

The excited state relaxation pathways of isoxazole and oxazole upon excitation with UV-light were investigated by nonadiabatic ab initio dynamics simulations and time-resolved photoelectron spectroscopy. Excitation of the bright ππ*-state of isoxazole predominantly leads to ring-opening dynamics. Both the initially excited ππ*-state and the dissociative πσ*-state offer a combined barrier-free reaction pathway, such that ring-opening, defined as a distance of more than 2 Å between two neighboring atoms, occurs within 45 fs. For oxazole, in contrast, the excited state dynamics is about twice as slow (85 fs) and the quantum yield for ring-opening is lower. This is caused by a small barrier between the ππ*-state and the πσ*-state along the reaction path, which suppresses direct ring-opening. Theoretical findings are consistent with the measured time-resolved photoelectron spectra, confirming the timescales and the quantum yields for the ring-opening channel. The results indicate that a combination of time-resolved photoelectron spectroscopy and excited state dynamics simulations can explain the dominant reaction pathways for this class of molecules. As a general rule, we suggest that the antibonding σ*-orbital located between the oxygen atom and a neighboring atom of a five-membered heterocyclic system provides a driving force for ring-opening reactions, which is modified by the presence and position of additional nitrogen atoms.

3.
J Chem Phys ; 152(6): 064301, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32061211

RESUMO

The influence of ring-puckering on the light-induced ring-opening dynamics of heterocyclic compounds was studied on the sample 5-membered ring molecules γ-valerolactone and 5H-furan-2-one using time-resolved photoelectron spectroscopy and ab initio molecular dynamics simulations. In γ-valerolactone, ring-puckering is not a viable relaxation channel and the only available reaction pathway is ring-opening, which occurs within one vibrational period along the C-O bond. In 5H-furan-2-one, the C=C double bond in the ring allows for ring-puckering which slows down the ring-opening process by about 150 fs while only marginally reducing its quantum yield. This demonstrates that ring-puckering is an ultrafast process, which is directly accessible upon excitation and which spreads the excited state wave packet quickly enough to influence even the outcome of an otherwise expectedly direct ring-opening reaction.

4.
J Chem Phys ; 150(24): 244704, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31255092

RESUMO

The temperature dependent dehydrogenation of naphthalene on Ni(111) has been investigated using vibrational sum-frequency generation spectroscopy, X-ray photoelectron spectroscopy, scanning tunneling microscopy, and density functional theory with the aim of discerning the reaction mechanism and the intermediates on the surface. At 110 K, multiple layers of naphthalene adsorb on Ni(111); the first layer is a flat lying chemisorbed monolayer, whereas the next layer(s) consist of physisorbed naphthalene. The aromaticity of the carbon rings in the first layer is reduced due to bonding to the surface Ni-atoms. Heating at 200 K causes desorption of the multilayers. At 360 K, the chemisorbed naphthalene monolayer starts dehydrogenating and the geometry of the molecules changes as the dehydrogenated carbon atoms coordinate to the nickel surface; thus, the molecule tilts with respect to the surface, recovering some of its original aromaticity. This effect peaks at 400 K and coincides with hydrogen desorption. Increasing the temperature leads to further dehydrogenation and production of H2 gas, as well as the formation of carbidic and graphitic surface carbon.

5.
Acta Paediatr ; 108(4): 688-693, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30265401

RESUMO

AIM: To study the prevalence of coeliac disease (CD) in children with Juvenile idiopathic arthritis (JIA), by screening a population-based cohort of children with JIA using autoantibodies against tissue transglutaminase (anti-TG2). METHODS: All children diagnosed with JIA in three Swedish counties, with disease onset between 2007 and 2014, were included prospectively. Serum levels of IgA anti-TG2 antibodies, IgG anti-TG2 antibodies, and total IgA were analysed. Children with positive levels of IgA anti-TG2 antibodies and children with IgA deficiency in combination with positive levels of IgG anti-TG2 antibodies were referred to the paediatric gastroenterology unit for gastroscopy and small intestine biopsy. RESULTS: A total of 216 children were included, and analysis of IgA and IgG anti-TG2 antibodies was performed in 213 children. Three children were diagnosed with CD prior to the diagnosis of JIA, and three additional children were found through screening, resulting in a CD point prevalence of 2.8% (95% CI 0.6-5.0%). CONCLUSION: We found a point prevalence of CD close to previous described prevalence in the general population of Swedish children. Therefore, general screening for CD in children with JIA is not supported by our data. However, this study shows that asymptomatic CD in children with JIA may be found by screening.


Assuntos
Artrite Juvenil/complicações , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Adolescente , Autoanticorpos/sangue , Doença Celíaca/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Proteínas de Ligação ao GTP/imunologia , Humanos , Imunoglobulina A/sangue , Masculino , Programas de Rastreamento , Prevalência , Proteína 2 Glutamina gama-Glutamiltransferase , Suécia/epidemiologia , Transglutaminases/imunologia
6.
Acta Oncol ; 57(2): 187-194, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28631533

RESUMO

BACKGROUND: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population. MATERIAL AND METHODS: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data. RESULTS: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort. CONCLUSIONS: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.


Assuntos
Bancos de Espécimes Biológicos/organização & administração , Biomarcadores Tumorais , Neoplasias , Humanos , Suécia
7.
Phys Chem Chem Phys ; 19(3): 2025-2035, 2017 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-28009022

RESUMO

For the series furan, furfural and ß-furfural we investigated the effect of substituents and their positioning on the photoinduced relaxation dynamics in a combined theoretical and experimental approach. Using time resolved photoelectron spectroscopy with a high intensity probe pulse, we can, for the first time, follow the whole deactivation process of furan through a two photon probe signal. Using the extended 2-electron 2-orbital model [Nenov et al., J. Chem. Phys., 2011, 135, 034304] we explain the formation of one central conical intersection and predict the influence of the aldehyde group of the derivatives on its geometry. This, as well as the relaxation mechanisms from photoexcitation to the final outcome was investigated using a variety of theoretical methods. Complete active space self consistent field was used for on-the-fly calculations while complete active space perturbation theory and coupled cluster theory were used to accurately describe critical configurations. Experiment and theory show the relaxation dynamics of furfural and ß-furfural to be slowed down, and together they disclose an additional deactivation pathway, which is attributed to the nO lonepair state introduced with the aldehyde group.

8.
J Chem Phys ; 146(14): 144307, 2017 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-28411588

RESUMO

The involvement of intermediate Rydberg states in the relaxation dynamics of small organic molecules which, after excitation to the valence manifold, also return to the valence manifold is rarely observed. We report here that such a transiently populated Rydberg state may offer the possibility to modify the outcome of a photochemical reaction. In a time resolved photoelectron study on pyrrole and its methylated derivatives, N-methyl pyrrole and 2,5-dimethyl pyrrole, 6.2 eV photons (200 nm) are used to excite these molecules into a bright ππ* state. In each case, a π3p-Rydberg state, either the B1(π3py) or the A2(π3pz) state, is populated within 20-50 fs after excitation. The wavepacket then proceeds to the lower lying A2(πσ*) state within a further 20 fs, at which point two competing reaction channels can be accessed: prompt N-H (N-CH3) bond cleavage or return to the ground state via a conical intersection accessed after ring puckering, the latter of which is predicted to require an additional 100-160 fs depending on the molecule.

9.
J Phys Chem A ; 120(15): 2320-9, 2016 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-27018427

RESUMO

We have reinvestigated the excited state dynamics of cyclohexa-1,3-diene (CHD) with time-resolved photoelectron spectroscopy and fewest switches surface hopping molecular dynamics based on linear response time-dependent density functional theory after excitation to the lowest lying ππ* (1B) state. The combination of both theory and experiment revealed several new results: First, the dynamics progress on one single excited state surface. After an incubation time of 35 ± 10 fs on the excited state, the dynamics proceed to the ground state in an additional 60 ± 10 fs, either via a conrotatory ring-opening to hexatriene or back to the CHD ground state. Moreover, ring-opening predominantly occurs when the wavepacket crosses the region of strong nonadiabatic coupling with a positive velocity in the bond alternation coordinate. After 100 fs, trajectories remaining in the excited state must return to the CHD ground state. This extra time delay induces a revival of the photoelectron signal and is an experimental confirmation of the previously formulated model of two parallel reaction channels with distinct time constants. Finally, our simulations suggest that after the initially formed cis-Z-cis HT rotamer the trans-Z-trans isomer is formed, before the thermodynamical equilibrium of three possible rotamers is reached after 1 ps.

10.
Scand J Clin Lab Invest ; 76(3): 208-16, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26924622

RESUMO

OBJECTIVES: IgA antibodies against tissue transglutaminase (anti-TG2) is a reliable marker of celiac disease (CD). However, IgA-deficient patients are not identified and young children may lack IgA anti-TG2. Combined detection of IgA and IgG (IgA/IgG) against deamidated gliadin peptides (DGP) has shown a high diagnostic performance for untreated CD. Here we examined the utility of IgA/IgG anti-TG2, IgA/IgG anti-DGP and IgA/IgG against a mix of TG2 and DGP (anti-TG2/DGP) in finding CD among children. METHODS: Serum antibodies against TG2, DGP, and TG2/DGP were determined with ELISA in 242 children referred to a paediatric gastroenterologist. Fifty had untreated CD verified by an intestinal biopsy and 192/242 children had other diseases than CD. RESULTS: Forty-eight untreated CD children had increased IgA/IgG anti-TG2, 47/50 had increased IgA/IgG anti-DGP and 46/50 had increased IgA/IgG anti-TG2/DGP. One control subject had increased IgA/IgG anti-TG2 and IgA/IgG anti-TG2/DGP, whereas 7/192 control subjects had increased IgA/IgG anti-DGP. The IgA/IgG anti-TG2 assay had the best performance with a sensitivity of 96%, a specificity of 99.5% and the area under the ROC-curve was 0.996 (95% CI 0.992-1, p < 0.0001). CONCLUSIONS: Detection of one antibody is not sufficient when screening for untreated CD among children due to cases of IgA deficiency. The inclusion of DGP antigens in the IgA/IgG combination assays seems to affect the sensitivity and specificity negatively, whereas detection of IgA/IgG anti-TG2 has the potential of finding most untreated CD patients, including those with IgA deficiency.


Assuntos
Autoanticorpos/sangue , Doença Celíaca/diagnóstico , Proteínas de Ligação ao GTP/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Transglutaminases/imunologia , Adolescente , Biópsia , Doença Celíaca/sangue , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Proteína 2 Glutamina gama-Glutamiltransferase , Curva ROC
11.
Scand J Clin Lab Invest ; 76(5): 393-401, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27223407

RESUMO

OBJECTIVE: Simple, objective and inexpensive tools for the assessment of mucosal inflammation in ulcerative colitis (UC) are highly desirable. The aim of this study was to evaluate a broad spectrum of activity markers comparing two sampling methods: fecal samples and the mucosal patch technique. METHODS: Twenty patients with active UC and 14 healthy controls were characterized by means of clinical indices and endoscopy together with histology and immunohistochemistry on colorectal sections. Neutrophil myeloperoxidase (MPO), calprotectin, eosinophil cationic protein (ECP), eosinophil protein X (EPX/EDN) and IL-1ß were analyzed in fecal samples and rectal fluid collected by the patch technique. Nitric oxide (NO) was analyzed in rectal gas samples. Expression of activity markers on colorectal neutrophils and eosinophils were analyzed by flow cytometry. RESULTS: All fecal and patch markers were increased in UC patients compared with healthy controls. Fecal markers and the level of neutrophil activation correlated to disease activity, whereas patch markers did not. The best markers in terms of discriminative power were fecal MPO and IL-1ß. Fecal marker levels were related to sigmoidal histology scores and to neutrophil number and activation. Patch markers were related to rectal inflammation only. CONCLUSIONS: The levels of inflammation markers in feces and patch fluid distinctly reflected active inflammation in UC. The degree of disease activity was however best assessed by fecal markers, particularly MPO and IL-1ß. Fecal markers reflect colorectal inflammation both macroscopically and on a cellular level, and may be useful for the evaluation of subclinical inflammation. The applicability of patch markers is restricted to rectal inflammation.


Assuntos
Biomarcadores , Colite Ulcerativa/metabolismo , Fezes , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Colite Ulcerativa/patologia , Colonoscopia , Proteína Catiônica de Eosinófilo/análise , Neurotoxina Derivada de Eosinófilo , Fezes/citologia , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Inflamação , Interleucina-1beta/análise , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade , Mucosa , Neutrófilos/patologia , Peroxidase/análise , Adulto Jovem
12.
Acta Paediatr ; 104(2): 185-91, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25283799

RESUMO

AIM: This study measured autoantibodies against tissue transglutaminase (anti-tTG) to detect untreated coeliac disease in children with type 1 diabetes and their siblings. METHODS: Anti-tTG was measured in prospectively collected sera from 169 children at the onset of diabetes, 88 of their siblings and 96 matched control children. Coeliac disease was confirmed with a small intestinal biopsy. RESULTS: Coeliac disease was diagnosed in five children before diabetes onset. A further 12 children were diagnosed after diabetes onset, without any gastrointestinal symptoms, and 11 of these had anti-tTG at the onset of diabetes, with the remaining child showing seroconversion within 6 months. Hence, all the children with both diseases had anti-tTG at or before diabetes diagnosis, and the prevalence of coeliac disease was 10.1%. Moreover, 6.8% of the siblings and 3.1% of the control children had elevated levels of anti-tTG. None of the siblings reported any coeliac-related symptoms, despite being positive for anti-tTG, and coeliac disease has so far been biopsy confirmed in 4.5%. CONCLUSION: Silent coeliac disease is over-represented in children with type 1 diabetes and their siblings. All diabetes children and their siblings should be tested and followed for the presence of anti-tTG and coeliac disease.


Assuntos
Doença Celíaca/complicações , Doença Celíaca/imunologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/imunologia , Proteínas de Ligação ao GTP/imunologia , Transglutaminases/imunologia , Adolescente , Autoanticorpos/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Celíaca/epidemiologia , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Humanos , Lactente , Masculino , Prevalência , Estudos Prospectivos , Proteína 2 Glutamina gama-Glutamiltransferase , Irmãos , Suécia/epidemiologia
13.
Hum Reprod ; 26(6): 1478-85, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21478181

RESUMO

UNLABELLED: BACKGROUND; Previous studies have indicated that peripheral circulating markers of inflammation are elevated in women with polycystic ovary syndrome (PCOS), but thus far no studies concerning markers of inflammation in adipose tissue have been published. The aim of the study was to investigate whether patients with PCOS display increased expression of inflammatory markers in adipose tissue. METHODS: Twenty overweight patients with PCOS, 10 lean patients with PCOS and 20 overweight controls had subcutaneous fat biopsies and blood samples taken. Adipose tissue levels of mRNA of inflammatory markers were determined by use of real-time PCR. RESULTS: Overweight patients with PCOS had higher relative adipose tissue chemokine ligand 2 (P < 0.01), and its cognate receptor (P < 0.05), tumour necrosis factor-α (P < 0.001), interleukin (IL)-10 (P < 0.001) and IL-18 (P < 0.001) and the monocyte/macrophage markers CD14 (P < 0.01) and CD163 (P < 0.01) mRNA levels compared with lean women with PCOS. There were no differences between overweight patients with PCOS and overweight control subjects in this respect. Within the PCOS group, markers of adipose tissue inflammation correlated significantly with obesity-related metabolic disturbances, but when data were adjusted for age and BMI, most correlations were lost. CONCLUSIONS: Overweight, rather than the PCOS diagnosis per se, appears to be the main explanatory variable for elevated adipose tissue inflammation in patients with PCOS.


Assuntos
Biomarcadores/sangue , Inflamação/sangue , Sobrepeso/sangue , Síndrome do Ovário Policístico/sangue , Gordura Subcutânea/metabolismo , Adulto , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Quimiocina CCL2/sangue , Feminino , Humanos , Interleucina-10/sangue , Interleucina-18/sangue , Receptores de Lipopolissacarídeos/sangue , RNA Mensageiro/metabolismo , Receptores CCR2/sangue , Receptores de Superfície Celular/sangue , Fator de Necrose Tumoral alfa/sangue
14.
Gynecol Endocrinol ; 27(7): 486-90, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20645890

RESUMO

INTRODUCTION: IgM antibodies against phosphorylcholine (IgM anti-PC) are natural autoantibodies, possibly exerting one of the atheroprotective functions of the immune system. Increased levels of these antibodies reduce the development of atherosclerosis in mice, and low levels of IgM anti-PC have been associated with increased risk for cardiovascular disease (CVD). This study compared levels of IgM anti-PC in women with polycystic ovary syndrome (PCOS, n = 111) and healthy controls (n = 79). METHOD: Levels of IgM anti-PC were measured with ELISA. RESULTS: The median level of IgM anti-PC in patients with PCOS was not significantly different compared to control subjects. However, the proportion of patients with PCOS with low levels of IgM anti-PC, defined as number of individuals below the median level, was significantly higher than among healthy controls, p < 0.05. Patients with PCOS in the oldest age quintile had significantly lower level of IgM anti-PC than control subjects of similar age (p < 0.05) and younger women with PCOS (p < 0.01). CONCLUSION: Our results indicate that women with PCOS more frequently display below-median levels of IgM anti-PC than controls and older women with PCOS have lower median anti-PC levels. Further studies of how this finding translates into actual CVD risk in women with PCOS are needed.


Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Imunoglobulina M/imunologia , Fosforilcolina/imunologia , Síndrome do Ovário Policístico/imunologia , Adulto , Anticorpos Anti-Idiotípicos/sangue , Feminino , Humanos , Imunoglobulina M/sangue , Pessoa de Meia-Idade , Fosforilcolina/sangue , Síndrome do Ovário Policístico/sangue
15.
J Pediatr Gastroenterol Nutr ; 50(2): 140-6, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19841593

RESUMO

OBJECTIVES: We analysed whether the quantification of autoantibodies against tissue transglutaminase could be used to predict mucosal destruction and disease severity in patients with gluten sensitivity. PATIENTS AND METHODS: One hundred seventy patients with coeliac disease (CD), comprising 52 children with severe malabsorption (group I), 59 children with mild symptoms (group II), 59 adults (group III), 134 patients with dermatitis herpetiformis (DH), and 131 disease controls, were studied. Serial serum samples of patients in groups I and II on a gluten-free diet were also included. Serum levels of antibodies against recombinant tissue transglutaminase were determined with ELISA using standard curves for quantification of antibodies. RESULTS: Immunoglobulin (Ig)A antibodies against tissue transglutaminase (IgA-TGA) were detected in all of the patients with CD and in 95% of the DH patients. The IgA-TGA and IgG-TGA levels were higher in group I (P < 0.001). The IgG-TGA levels and positivity rate in group I (100%) were higher than in group II (81%), group III (73%), and the DH group (67%). Elevated IgA-TGA and IgG-TGA levels in combination predicted a more severe small intestinal atrophy (P < 0.0001) with a specificity of 99% for Marsh IIIb-IIIc (flat) lesions. The kinetics of the IgA-TGA decrease during diet differed between groups I and II. CONCLUSIONS: High levels of IgA-TGA and IgG-TGA antibodies were associated with the grade of mucosal villous atrophy and a more severe clinical presentation. The combined measurement of IgA-TGA and IgG-TGA enables a noninvasive prediction of small intestinal villous atrophy with high accuracy, and may reduce the need for a biopsy in patients with suspected CD.


Assuntos
Autoanticorpos/sangue , Doença Celíaca/imunologia , Dermatite Herpetiforme/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Mucosa Intestinal/patologia , Transglutaminases/imunologia , Adolescente , Adulto , Idoso , Doença Celíaca/enzimologia , Doença Celíaca/patologia , Criança , Pré-Escolar , Dermatite Herpetiforme/enzimologia , Dermatite Herpetiforme/patologia , Ensaio de Imunoadsorção Enzimática , Humanos , Intestino Delgado/patologia , Pessoa de Meia-Idade , Adulto Jovem
16.
Clin Chim Acta ; 395(1-2): 72-6, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18514068

RESUMO

OBJECTIVES: To investigate if the detection of celiac disease (CD) in children was improved by using alternative conjugates for assessment of tissue transglutaminase (tTG) autoantibodies. METHODS: Serum samples from 108 biopsy confirmed CD children and 42 control subjects were investigated for the presence of autoantibodies with tTG coated microplates using protein A (PA), protein G (PG), anti-IgG, or anti-IgA as conjugates. RESULTS: Of the 108 CD children, 86 (80%) were IgG-tTG positive, 91 (84%) were positive with the PA-conjugate, 94 (87%) were positive with the PG-conjugate, and 103 (95%) were IgA-tTG positive. Among the 42 controls, 4 (10%) were IgG-tTG positive, 5 (12%) were positive with both the PA- and PG conjugates, whereas 3 (7%) were IgA-tTG positive. Compared with IgG-tTG the concordance was 93% for PA and 95% for PG, with a positive correlation between antibody levels (r=0.967 and r=0.975, p<0.0001). All but one CD child were found positive by combining IgG-tTG and IgA-tTG detection. CONCLUSIONS: The sensitivity of IgG-tTG detection with ELISA increased by protein A or protein G conjugates, whereas the specificity was reduced as compared with anti-IgG conjugate. The combined measurement of IgA-tTG and IgG-tTG still seems to be the optimal procedure when screening children for CD.


Assuntos
Autoanticorpos/sangue , Doença Celíaca/sangue , Proteínas de Ligação ao GTP/imunologia , Imunoglobulina G/sangue , Proteínas do Tecido Nervoso/química , Proteína Estafilocócica A/química , Transglutaminases/imunologia , Adolescente , Adulto , Doença Celíaca/imunologia , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Imunoglobulina A/sangue , Lactente , Masculino , Proteína 2 Glutamina gama-Glutamiltransferase , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
J Pediatr Gastroenterol Nutr ; 47(4): 428-35, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18852634

RESUMO

OBJECTIVES: The aim was to investigate age-dependent serum levels and occurrence of elevated celiac disease (CD)-related antibodies in young children, to define the optimal serological procedure when selecting for small intestinal biopsy. PATIENTS AND METHODS: Included were 428 children with biopsy verified CD (median age 16 months; range 7.5 months-14 years) and 216 controls (median age 2.7 years; range 8.5 months-14.6 years). Immunoglobulin (Ig) A antibodies against gliadin (AGA-IgA), tissue transglutaminase (tTG-IgA), and endomysium (EMA-IgA) were analysed. RESULTS: Increased serum AGA-IgA levels were found in 411 of 428 CD cases, tTG-IgA in 385 of 428, and EMA-IgA in 383 of 428. In the control group, 11 of 216 had increased levels of AGA-IgA, 5 of 216 of tTG-IgA, and 8 of 216 of EMA-IgA. In CD children younger than 18 months, elevated AGA-IgA occurred in 97% and elevated tTG-IgA and EMA-IgA were found in 83% of the cases. Conversely, in CD children older than 18 months, elevated AGA-IgA occurred in 94%, and elevated tTG-IgA and EMA-IgA were found in 99% of the cases. CONCLUSIONS: In children older than 18 months, both tTG-IgA and EMA-IgA are sufficiently accurate to be used as a single antibody marker, whereas a large proportion of younger children with CD lack these antibodies. Therefore, when selecting children for small intestinal biopsy, the detection of a combination of AGA-IgA and tTG-IgA is optimal for identifying untreated CD in children younger than 18 months.


Assuntos
Doença Celíaca/sangue , Doença Celíaca/imunologia , Gliadina/imunologia , Imunoglobulina A/sangue , Transglutaminases/imunologia , Adolescente , Fatores Etários , Autoanticorpos/análise , Autoanticorpos/sangue , Biomarcadores/sangue , Biópsia/métodos , Estudos de Casos e Controles , Doença Celíaca/diagnóstico , Doença Celíaca/patologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Gliadina/análise , Humanos , Lactente , Intestino Delgado/patologia , Masculino , Estudos Prospectivos , Sensibilidade e Especificidade
18.
N Engl J Med ; 348(25): 2517-24, 2003 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-12815137

RESUMO

BACKGROUND: Wheat, rye, and barley proteins induce celiac disease, an autoimmune type of gastrointestinal disorder, in genetically susceptible persons. Because the disease may be underdiagnosed, we estimated the prevalence of the disease and tested the hypothesis that assays for serum autoantibodies can be used to detect untreated celiac disease and that positive findings correlate with specific HLA haplotypes. METHODS: Serum samples were collected from 3654 students (age range, 7 to 16 years) in 1994 and screened in 2001 for endomysial and tissue transglutaminase antibodies. HLA typing was also performed on stored blood samples. All antibody-positive subjects were asked to undergo small-bowel biopsy in 2001. RESULTS: Of the 3654 subjects, 56 (1.5 percent) had positive antibody tests, as determined in 2001. Results of the two antibody tests were highly concordant. As of 1994, none of the subjects had received a clinical diagnosis of celiac disease, but 10 who had positive tests for both antibodies in serum obtained in 1994 received the diagnosis between 1994 and 2001. Of the 36 other subjects with positive antibody assays who agreed to undergo biopsy in 2001, 27 had evidence of celiac disease on biopsy. Thus, the estimated biopsy-proved prevalence was 1 case in 99 children. All but two of the antibody-positive subjects had either the HLA-DQ2 or the HLA-DQ8 haplotype. The prevalence of the combination of antibody positivity and an HLA haplotype associated with celiac disease was 1 in 67. CONCLUSIONS: The presence of serum tissue transglutaminase and endomysial autoantibodies is predictive of small-bowel abnormalities indicative of celiac disease. There is a good correlation between autoantibody positivity and specific HLA haplotypes. We estimate that the prevalence of celiac disease among Finnish schoolchildren is at least 1 case in 99 children.


Assuntos
Autoanticorpos/sangue , Doença Celíaca/epidemiologia , Fibras Musculares Esqueléticas/imunologia , Transglutaminases/imunologia , Adolescente , Biópsia , Doença Celíaca/diagnóstico , Doença Celíaca/imunologia , Criança , Estudos de Coortes , Feminino , Finlândia/epidemiologia , Teste de Histocompatibilidade , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Intestino Delgado/patologia , Masculino , Mucosa Nasal/anatomia & histologia , Prevalência
19.
Artigo em Inglês | MEDLINE | ID: mdl-23986895

RESUMO

BACKGROUND: Atopic allergy is effected by a number of environmental exposures, such as dry air and time spent outdoors, but there are few estimates of the prevalence in populations from sub-arctic areas. OBJECTIVE: To determine the prevalence and severity of symptoms of food, inhalation and skin-related allergens and coeliac disease (CD) in the sub-arctic region of Sweden. To study the correlation between self-reported allergy and allergy test results. To estimate the heritability of these estimates. STUDY DESIGN: The study was conducted in Karesuando and Soppero in Northern Sweden as part of the Northern Sweden Population Health Study (n=1,068). We used a questionnaire for self-reported allergy and CD status and measured inhalation-related allergens using Phadiatop, food-related allergens using the F × 5 assay and IgA and IgG antibodies against tissue transglutaminase (anti-tTG) to indicate prevalence of CD. RESULTS: The prevalence of self-reported allergy was very high, with 42.3% reporting mild to severe allergy. Inhalation-related allergy was reported in 26.7%, food-related allergy in 24.9% and skin-related allergy in 2.4% of the participants. Of inhalation-related allergy, 11.0% reported reactions against fur and 14.6% against pollen/grass. Among food-related reactions, 14.9% reported milk (protein and lactose) as the cause. The IgE measurements showed that 18.4% had elevated values for inhalation allergens and 11.7% for food allergens. Self-reported allergies and symptoms were positively correlated (p<0.01) with age- and sex-corrected inhalation allergens. Allergy prevalence was inversely correlated with age and number of hours spent outdoors. High levels of IgA and IgG anti-tTG antibodies, CD-related allergens, were found in 1.4 and 0.6% of participants, respectively. All allergens were found to be significantly (p<3 e-10) heritable, with estimated heritabilities ranging from 0.34 (F × 5) to 0.65 (IgA). CONCLUSIONS: Self-reported allergy correlated well with the antibody measurements. The prevalence of allergy was highest in the young and those working inside. Heritability of atopy and sensitization was high. The prevalence of CD-related autoantibodies was high and did not coincide with the self-reported allergy.


Assuntos
Doença Celíaca/epidemiologia , Hipersensibilidade Imediata/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Alérgenos/imunologia , Dermatite Atópica/epidemiologia , Feminino , Hipersensibilidade Alimentar/epidemiologia , Humanos , Hipersensibilidade Imediata/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , Hipersensibilidade Respiratória/epidemiologia , Inquéritos e Questionários , Suécia/epidemiologia , Adulto Jovem
20.
Scand J Gastroenterol ; 41(1): 54-9, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16373277

RESUMO

OBJECTIVE: Irritable bowel syndrome (IBS) and collagenous colitis (CC) share chronically recurring symptoms of altered bowel habits associated with abdominal pain or discomfort. The aims of the present study were to investigate whether inflammatory markers could be detected in faeces from patients with IBS and CC, and to elucidate whether such analyses could be used as non-invasive tools to distinguish between these disorders. MATERIAL AND METHODS: Stool samples were obtained from 18 patients with CC, 46 patients with IBS and 20 healthy controls (HC). Eosinophil protein X (EPX), myeloperoxidase (MPO), tryptase, interleukin-1 beta (IL-1beta) and tumour necrosis factor alpha (TNFalpha) were measured in supernatants from processed faeces using immunoassays. RESULTS: EPX levels were enhanced in faeces from CC patients (median 3.8 microg/g (0.47-16.2)) compared to patients with IBS (0.44 microg/g (0.25-1.8)), p<0.001, and HC (0.46 microg/g (0.21-1.3)), p<0.001. In addition, MPO was increased in CC patients (11.7 microg/g (2.0-124)) compared to IBS patients (1.7 microg/g (0.81-5.2)), p<0.01, and HC (2.5 microg/g (1.1-6.3)), p<0.05. Tryptase was found in 9/18 patients with CC, 6/46 with IBS and 1/19 HC. IL-1beta was only enhanced in 2/11 CC patients and TNFalpha was not detected in any sample. CONCLUSIONS: Increased levels of EPX, MPO and tryptase were observed in stools from collagenous colitis patients, whereas the levels in IBS patients did not differ from healthy controls. Our data suggest that faecal markers could be used as part of the clinical work-up to determine which patients should be biopsied and evaluated for collagenous colitis.


Assuntos
Biomarcadores/análise , Colite Colagenosa/metabolismo , Fezes/química , Síndrome do Intestino Irritável/metabolismo , Adulto , Idoso , Colite Colagenosa/diagnóstico , Diagnóstico Diferencial , Neurotoxina Derivada de Eosinófilo/análise , Feminino , Humanos , Imunoensaio , Inflamação , Interleucina-1/análise , Síndrome do Intestino Irritável/diagnóstico , Masculino , Pessoa de Meia-Idade , Peroxidase/análise , Serina Endopeptidases/análise , Triptases , Fator de Necrose Tumoral alfa/análise
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