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1.
Clin Rheumatol ; 38(2): 331-338, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30073458

RESUMO

Immunoglobulin A vasculitis (IgAV) is an immune complex, small vessel vasculitis with dominant IgA deposits in vessel walls, predominantly affecting the pediatric population. However, adults frequently have more severe gastrointestinal tract (GIT) and renal involvements as compared to children. Our aim was to study serological and cellular biomarkers to support clinicians in their diagnosis and the course of IgAV in adult patients. This cross-sectional study included 62 adult IgAV patients and 53 healthy blood donors (HBDs). Demographic and clinical data, as well as routine laboratory tests, were meticulously analyzed. Serum levels of IL-1ß, IL-2, IL-6, IL-8, IL-9, IL-10, IL-17A, IL-23, TNF-α and serum amyloid A (SAA) were measured. Percentages of neutrophils, lymphocytes, and monocytes with neutrophil expression of L-selectin and integrin αM were determined by flow cytometry. SAA (12-fold), IL-6 (3-fold), IL-8 (2-fold), and TNF-α (2-fold) were significantly elevated in sera of adult IgAV patients compared to HBDs. There was a 16% elevation in neutrophils in IgAV patients, with IgAV neutrophils showing significantly higher CD62L surface expression. IgAV patients with GIT involvement exhibited elevated numbers of leukocytes, neutrophils, and neutrophil/lymphocyte (NLR), but lower neutrophil CD11b expression, as compared to IgAV patients without GIT. IgAV patients exhibit a low-medium grade inflammatory, neutrophil-driven response. Patients with GIT can be distinguished by their elevated NLR.


Assuntos
Citocinas/sangue , Vasculite por IgA/sangue , Imunoglobulina A/sangue , Neutrófilos/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Antígeno CD11b/sangue , Estudos de Casos e Controles , Estudos Transversais , Feminino , Citometria de Fluxo , Humanos , Vasculite por IgA/imunologia , Imunoglobulina A/imunologia , Selectina L/sangue , Masculino , Pessoa de Meia-Idade
2.
J Biol Regul Homeost Agents ; 32(2): 313-319, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29685012

RESUMO

In patients with giant cell arteritis (GCA), autoantibodies against cytoskeletal elements, cardiolipin, neutrophil cytoplasmic antigens, ferritin, endothelial and smooth muscle cells have been reported, however no updated reviews are available evaluating their clinical utility. Methodology of detection is important, especially for quantitative assays, e.g. enzyme-linked immunoassays and multiplex beadbased immunoassays, while semiquantitative assays contribute valuable data on isoforms, epitope mapping and cellular localization. Most studies to date reporting on antiphospholipid antibodies in GCA have focused on anti-cardiolipin antibodies (aCL), while the highest prevalence of autoantibodies in GCA patients was reported for the anti-N-terminal peptides of the ferritin heavy chain (92%). Antineutrophil cytoplasmic antibodies were shown to be present in only a small percentage of GCA patients, decreasing after therapy, however in combination with aCL and antibodies against peptides of N-terminal ferritin heavy chain, they could represent an added value in detecting relapse in GCA patients.


Assuntos
Autoanticorpos/sangue , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/imunologia , Arterite de Células Gigantes/sangue , Humanos , Recidiva
3.
Autoimmun Rev ; 17(2): 188-194, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29196244

RESUMO

Giant cell arteritis (GCA) is a primary systemic vasculitis present in subjects older than 50years with involvement of large- and medium-sized arteries. Early diagnosis for GCA is essential to prevent serious complications, such as permanent vision loss and/or cerebrovascular events. Elevated inflammatory cytokines, with acute phase and other proteins dominate large- and medium-sized arteries leading to stenosis or occlusion of arterial lumen. To date, there are no reliable serological markers for monitoring GCA. The review aims to provide concise overview of published GCA studies in order to: a) identify significantly changed serological biomarkers in GCA and compare the influences of techniques for marker evaluation and b) investigate most promising markers in GCA using analyte frequency and meta-analysis.


Assuntos
Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Arterite de Células Gigantes/diagnóstico , Humanos
4.
Scand J Rheumatol ; 45(5): 347-55, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26726793

RESUMO

OBJECTIVES: The mechanism by which methotrexate (MTX) improves glucose homeostasis in patients with rheumatoid (RA) and psoriatic arthritis (PsA) remains undetermined. Animal studies indicate a role for intracellular accumulation of 5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranosyl 5'-monophosphate (ZMP) but this has not been directly demonstrated in humans. We explored whether accumulation of ZMP is associated with improvements in glucose homeostasis during MTX therapy. METHOD: MTX-naïve, non-diabetic RA (n = 16) and PsA (n = 10) patients received uninterrupted MTX treatment for 6 months. To evaluate whether ZMP accumulated during MTX therapy, we measured the concentration of ZMP in erythrocytes and the concentration of its dephosphorylated derivative 5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside (AICAR) in urine using liquid chromatography mass spectrometry (LC-MS/MS). To assess glucose homeostasis, we determined the concentration of glycated haemoglobin (HbA1c) and homeostasis model assessment of insulin resistance [HOMA-IR: fasting glucose (mmol/L) × fasting insulin (µU/mL)/22.5]. RESULTS: Erythrocyte ZMP and urinary AICAR concentrations did not increase during 6 months of MTX therapy. HbA1c concentration was reduced from 5.80 ± 0.29% at baseline to 5.51 ± 0.32% at 6 months (p < 0.001), while HOMA-IR remained unaltered. Reduction in HbA1c concentration was not associated with increased ZMP or AICAR concentrations. CONCLUSIONS: MTX therapy probably does not produce a chronic increase in erythrocyte ZMP or urinary AICAR concentrations. Collectively, our data do not support the hypothesis that MTX improves glucose homeostasis through chronic accumulation of ZMP.


Assuntos
Aminoimidazol Carboxamida/análogos & derivados , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Glicemia/metabolismo , Hemoglobinas Glicadas/metabolismo , Insulina/metabolismo , Metotrexato/uso terapêutico , Ribonucleotídeos/metabolismo , Adulto , Idoso , Aminoimidazol Carboxamida/metabolismo , Artrite Psoriásica/metabolismo , Artrite Reumatoide/metabolismo , Cromatografia Líquida , Eritrócitos/metabolismo , Feminino , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espectrometria de Massas em Tandem
5.
Br J Dermatol ; 171(3): 524-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24601900

RESUMO

BACKGROUND: IgA vasculitis (IgAV) is assumed to be uncommon in adults. OBJECTIVES: To determine the incidence rate of histologically proven IgAV in the adult Slovenian population. METHODS: A retrospective chart review of adult patients diagnosed with IgAV was performed at the departments of rheumatology, nephrology, infectious diseases and dermatovenereology at an integrated secondary/tertiary university teaching hospital. In order to avoid missing miscoded cases, the Institute of Pathology, University of Ljubljana, Slovenia, provided a list of all patients with an IgAV-compatible histological pattern on biopsy. The annual incidence rate of histologically proven IgAV was calculated. RESULTS: Eighty-one new cases of IgAV were identified from June 2010 to June 2013. The estimated annual incidence rate of IgAV was 5·1 per 100,000 adults [95% confidence interval (CI) 3·4-7·4]; in men it was 6·1 per 100,000 (95% CI 3·9-10·6) and in women it was 3·7 per 100,000 (95% CI 1·8-6·8). CONCLUSIONS: Although we only included histologically proven cases of IgAV, the annual incidence rate of 5·1 per 100,000 adults is 3-6-times higher than previously reported.


Assuntos
Imunoglobulina A , Vasculite/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição por Sexo , Eslovênia/epidemiologia , Adulto Jovem
6.
Case Rep Dermatol ; 5(3): 309-15, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24348379

RESUMO

Scleromyxedema is a rare cutaneous mucinosis, usually presenting with generalized papular eruption and sclerodermoid induration, monoclonal gammopathy and systemic manifestations. An atypical clinical presentation with cutaneous and subcutaneous nodules has been reported rarely. In recent years, intravenous immunoglobulin (IVIg) appears to be the therapy of choice for scleromyxedema. Treatment experiences in atypical manifestations with mucinous nodules are limited to sporadic reports. We report the case of male patient with atypical scleromyxedema without underlying paraproteinemia, presenting with generalized papular and sclerodermoid skin eruption and multiple nodular mucinous lesions on the fingers and face as well as on the eyelids, and associated systemic symptoms. Complete regression of all cutaneous lesions and extracutaneous symptoms with sustained remission was achieved by combined treatment with thalidomide and IVIg.

7.
Phys Rev E Stat Nonlin Soft Matter Phys ; 83(4 Pt 1): 041917, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21599210

RESUMO

We theoretically study the structure of periodic bulk assemblies of identical lipid vesicles. In our model, each vesicle is represented as a convex polyhedron with flat faces, rounded edges, and rounded vertices. Each vesicle carries an elastic and an adhesion energy and in the limit of strong adhesion, the minimal-energy shape of cells minimizes the weighted total edge length. We calculate exactly the shape of the rounded edge and show that it can be well described by a cylindrical surface. By comparing several candidate space-filling polyhedra, we find that the oblate shapes are preferred over prolate shapes for all volume-to-surface ratios. We also study periodic assemblies of vesicles whose adhesion strength on lateral faces is different from that on basal or apical faces. The anisotropy needed to stabilize prolate shapes is determined and it is shown that, at any volume-to-surface ratio, the transition between oblate and prolate shapes is very sharp. The geometry of the model vesicle assemblies reproduces the shapes of cells in certain simple animal tissues.


Assuntos
Bicamadas Lipídicas/química , Fluidez de Membrana , Modelos Químicos , Modelos Moleculares , Lipossomas Unilamelares/química , Simulação por Computador
8.
Eur Phys J E Soft Matter ; 33(4): 369-75, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21107883

RESUMO

A vast range of both living and inanimate planar cellular partitions obeys universal empirical laws describing their structure. To better understand this observation, we analyze the morphometric parameters of a sizeable set of experimental data that includes animal and plant tissues, patterns in desiccated starch slurry, suprafroth in type-I superconductors, soap froths, and geological formations. We characterize the tilings by the distributions of polygon reduced area, a scale-free measure of the roundedness of polygons. These distributions are fairly sharp and seem to belong to the same family. We show that the experimental tilings can be mapped onto the model tilings of equal-area, equal-perimeter polygons obtained by numerical simulations. This suggests that the random two-dimensional patterns can be parametrized by their median reduced area alone.


Assuntos
Drosophila/citologia , Células Epiteliais/citologia , Modelos Biológicos , Animais , Forma Celular , Drosophila/classificação , Drosophila/fisiologia , Células Epiteliais/classificação , Células Epiteliais/fisiologia
9.
Phys Rev E Stat Nonlin Soft Matter Phys ; 80(1 Pt 1): 011904, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19658726

RESUMO

The salient feature of one-cell-thick epithelia is their en face view, which reveals the polygonal cross section of the close-packed prismatic cells. The physical mechanisms that shape these tissues were hitherto explored using theories based on cell proliferation, which were either entirely topological or included certain morphogenetic forces. But mitosis itself may not be instrumental in molding the tissue. We show that the structure of simple epithelia can be explained by an equilibrium model where energy-degenerate polygons in an entropy-maximizing tiling are described by a single geometric parameter encoding their inflation. The two types of tilings found numerically--ordered and disordered--closely reproduce the patterns observed in Drosophila, Hydra, and Xenopus and they generalize earlier theoretical results. Free of a specific cell self-energy, cell-cell interaction, and cell division kinetics, our model provides an insight into the universality of living and inanimate two-dimensional cellular structures.


Assuntos
Células Epiteliais/citologia , Modelos Biológicos , Animais , Agregação Celular , Forma Celular , Drosophila/citologia , Entropia , Hydra/citologia , Ratos , Xenopus
12.
Rheumatology (Oxford) ; 44(6): 768-72, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15741192

RESUMO

OBJECTIVES: To reveal typical ultrasonographic (US) changes in major salivary glands associated with Sjogren's syndrome (SS) and to determine the diagnostic value of a novel US scoring system. METHODS: In 218 consecutive patients with suspected SS, US of both parotid and submandibular salivary glands was performed besides the regular diagnostic procedure following the American-European Consensus Group criteria of 2002. Five US parameters were assessed: echogenicity, inhomogeneity, number of hypoechogenic areas, the hyperechogenic reflections and clearness of the borders of the salivary gland. The grades of these five parameters for all four salivary glands were summed. The final US score ranged from 0 to 48. RESULTS: SS was established in 68 patients. The remaining 150 subjects, in whom SS was not confirmed, constituted our control group. All five US parameters were significantly associated with SS. The patients with SS had significantly higher US scores than those not diagnosed with SS (P<0.01). Setting the cut-off US score at 17 resulted in the best ratio of specificity (98.7%) to sensitivity (58.8%). CONCLUSIONS: Well-defined US changes in the major salivary glands summarized in our novel scoring system were typical of SS patients. Advanced structural changes found on US imaging almost invariably represent SS salivary gland involvement.


Assuntos
Glândulas Salivares/diagnóstico por imagem , Síndrome de Sjogren/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glândula Parótida/diagnóstico por imagem , Curva ROC , Glândula Submandibular/diagnóstico por imagem , Ultrassonografia
13.
Ann Rheum Dis ; 63(7): 874-6, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15194588

RESUMO

OBJECTIVE: To determine the annual incidence of primary Sjögren's syndrome (pSS) in Slovenia. METHODS: All patients admitted to our department of rheumatology or referred to our outpatient clinic between 1 January 2000 and 31 December 2002 owing to sicca symptoms or because of a suspicion of SS were examined. Our rheumatological department is the only tertiary referral centre for the Ljubljana region, which has a population of 599 895 Caucasian people. All patients were evaluated by the validated European criteria for SS. The exact 95% confidence interval (CI) based on binomial distribution was created for the incidence estimate. RESULTS: 248 patients were examined; 71 of them (28.6%; 65 women, 6 men) were diagnosed as having pSS. Their mean (SD) age was 51.3 (14.5) years (range 19-78). The average annual incidence for pSS in our study population was calculated as 3.9 cases per 100 000 inhabitants (95% CI 1.1 to 10.2). CONCLUSION: The estimated annual incidence of pSS in Slovenia is 3.9/100 000.


Assuntos
Síndrome de Sjogren/epidemiologia , Adulto , Idoso , Intervalos de Confiança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Síndrome de Sjogren/diagnóstico , Eslovênia/epidemiologia
14.
Ann Rheum Dis ; 62(8): 702-4, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12860722

RESUMO

In the past sicca syndromes were attributed to destruction of glandular tissue. It is now thought that cytokines, autoantibodies, and parasympathetic nervous system dysfunction all have an important role in the xerostomia and xerophthalmia in Sjögren's syndrome.


Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Sistema Nervoso Parassimpático/fisiopatologia , Síndrome de Sjogren/fisiopatologia , Humanos , Transmissão Sináptica , Xeroftalmia/fisiopatologia , Xerostomia/fisiopatologia
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