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1.
J Cell Mol Med ; 23(6): 3962-3973, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30941904

RESUMO

Intrauterine growth restriction (IUGR) is an obstetric complication characterised by placental insufficiency and secondary cardiovascular remodelling that can lead to cardiomyopathy in adulthood. Despite its aetiology and potential therapeutics are poorly understood, bioenergetic deficits have been demonstrated in adverse foetal and cardiac development. We aimed to evaluate the role of mitochondria in human pregnancies with IUGR. In a single-site, cross-sectional and observational study, we included placenta and maternal peripheral and neonatal cord blood mononuclear cells (PBMC and CBMC) from 14 IUGR and 22 control pregnancies. The following mitochondrial measurements were assessed: enzymatic activities of mitochondrial respiratory chain (MRC) complexes I, II, IV, I + III and II + III, oxygen consumption (cell and complex I-stimulated respiration), mitochondrial content (citrate synthase [CS] activity and mitochondrial DNA copy number), total ATP levels and lipid peroxidation. Sirtuin3 expression was evaluated as a potential regulator of bioenergetic imbalance. Intrauterine growth restriction placental tissue showed a significant decrease of MRC CI enzymatic activity (P < 0.05) and CI-stimulated oxygen consumption (P < 0.05) accompanied by a significant increase of Sirtuin3/ß-actin protein levels (P < 0.05). Maternal PBMC and neonatal CBMC from IUGR patients presented a not significant decrease in oxygen consumption (cell and CI-stimulated respiration) and MRC enzymatic activities (CII and CIV). Moreover, CS activity was significantly reduced in IUGR new-borns (P < 0.05). Total ATP levels and lipid peroxidation were preserved in all the studied tissues. Altered mitochondrial function of IUGR is especially present at placental and neonatal level, conveying potential targets to modulate obstetric outcome through dietary interventions aimed to regulate Sirtuin3 function.

2.
Front Immunol ; 9: 809, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29731755

RESUMO

Background: Giant-cell arteritis (GCA) is considered a T helper (Th)1- and Th17-mediated disease. Interleukin (IL)-12 is a heterodimeric cytokine (p35/p40) involved in Th1 differentiation. When combining with p19 subunit, p40 compose IL-23, a powerful pro-inflammatory cytokine that maintains Th17 response. Objectives: The aims of this study were to investigate p40, p35, and p19 subunit expression in GCA lesions and their combinations to conform different cytokines, to assess the effect of glucocorticoid treatment on subunit expression, and to explore functional roles of p40 by culturing temporal artery sections with a neutralizing anti-human IL-12/IL-23p40 antibody. Methods and results: p40 and p19 mRNA concentrations measured by real-time RT-PCR were significantly higher in temporal arteries from 50 patients compared to 20 controls (4.35 ± 4.06 vs 0.51 ± 0.75; p < 0.0001 and 20.32 ± 21.78 vs 4.17 ± 4.43 relative units; p < 0.0001, respectively). No differences were found in constitutively expressed p35 mRNA. Contrarily, p40 and p19 mRNAs were decreased in temporal arteries from 16 treated GCA patients vs those from 34 treatment-naïve GCA patients. Accordingly, dexamethasone reduced p40 and p19 expression in cultured arteries. Subunit associations to conform IL-12 and IL-23 were confirmed by proximity-ligation assay in GCA lesions. Immunofluorescence revealed widespread p19 and p35 expression by inflammatory cells, independent from p40. Blocking IL-12/IL-23p40 tended to reduce IFNγ and IL-17 mRNA production by cultured GCA arteries and tended to increase Th17 inducers IL-1ß and IL-6. Conclusion: IL-12 and IL-23 heterodimers are increased in GCA lesions and decrease with glucocorticoid treatment. p19 and p35 subunits are much more abundant than p40, indicating an independent role for these subunits or their potential association with alternative subunits. The modest effect of IL-12/IL-23p40 neutralization may indicate compensation by redundant cytokines or cytokines resulting from alternative combinations.


Assuntos
Arterite de Células Gigantes/imunologia , Subunidade p35 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/genética , Subunidade p19 da Interleucina-23/genética , Células Th1/imunologia , Células Th17/imunologia , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Citocinas , Feminino , Arterite de Células Gigantes/patologia , Glucocorticoides/uso terapêutico , Humanos , Subunidade p35 da Interleucina-12/imunologia , Subunidade p40 da Interleucina-12/imunologia , Subunidade p19 da Interleucina-23/imunologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Artérias Temporais/efeitos dos fármacos , Artérias Temporais/imunologia , Células Th1/efeitos dos fármacos , Células Th17/efeitos dos fármacos
4.
J Antimicrob Chemother ; 72(9): 2578-2586, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28859443

RESUMO

Background: HIV infection and HAART trigger genetic and functional mitochondrial alterations leading to cell death and adverse clinical manifestations. Mitochondrial dynamics enable mitochondrial turnover and degradation of damaged mitochondria, which may lead to apoptosis. Objectives: To evaluate markers of mitochondrial dynamics and apoptosis in pregnancies among HIV-infected women on HAART and determine their potential association with obstetric complications. Methods: This controlled, single-site, observational study without intervention included 26 HIV-infected pregnant women on HAART and 18 control pregnancies and their newborns. Maternal PBMCs and neonatal cord blood mononuclear cells (CBMCs) were isolated at the first trimester of gestation and at delivery. The placenta was homogenized at 5% w/v. Mitochondrial dynamics, fusion events [mitofusin 2 (Mfn2)/ß-actin] and fission events [dynamin-related protein 1 (Drp1/ß-actin)] and apoptosis (caspase 3/ß-actin) were assessed by western blot analysis. Results: Obstetric complications were significantly more frequent in pregnancies among HIV-infected women [OR 5.00 (95% CI 1.21-20.70)]. Mfn2/ß-actin levels in PBMCs from controls significantly decreased during pregnancy (202.13 ±â€¯57.45%), whereas cases maintained reduced levels from the first trimester of pregnancy and no differences were observed in CBMCs. Mfn2/ß-actin and Drp1/ß-actin contents significantly decreased in the placenta of cases. Caspase 3/ß-actin levels significantly increased during pregnancy in PBMCs of cases (50.00 ±â€¯7.89%), remaining significantly higher than in controls. No significant differences in caspase 3/ß-actin content of neonatal CBMCs were observed, but there was a slight increased trend in placenta from cases. Conclusions: HIV- and HAART-mediated mitochondrial damage may be enhanced by decreased mitochondrial dynamics and increased apoptosis in maternal and placental compartments but not in the uninfected fetus. However, direct effects on mitochondrial dynamics and implication of apoptosis were not demonstrated in adverse obstetric outcomes.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Apoptose/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Dinâmica Mitocondrial/efeitos dos fármacos , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Adulto , Fármacos Anti-HIV/uso terapêutico , Caspase 3/genética , Feminino , GTP Fosfo-Hidrolases/genética , Infecções por HIV/virologia , Humanos , Recém-Nascido , Leucócitos Mononucleares , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/genética , Placenta/fisiologia , Gravidez , Complicações Infecciosas na Gravidez/virologia
5.
Arthritis Res Ther ; 19(1): 174, 2017 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-28738907

RESUMO

BACKGROUND: Dermatomyositis (DM) is inflammatory myopathy or myositis characterized by muscle weakness and skin manifestations. In the differential diagnosis of DM the evaluation of the muscle biopsy is of importance among other parameters. Perifascicular atrophy in the muscle biopsy is considered a hallmark of DM. However, perifascicular atrophy is not observed in all patients with DM and, conversely, perifascicular atrophy can be observed in other myositis such as antisynthetase syndrome (ASS), complicating DM diagnosis. Retinoic acid inducible-gene I (RIG-I), a receptor of innate immunity that promotes type I interferon, was observed in perifascicular areas in DM. We compared the value of RIG-I expression with perifascicular atrophy as a biomarker of DM. METHODS: We studied by immunohistochemical analysis the expression of RIG-I and the presence of perifascicular atrophy in 115 coded muscle biopsies: 44 patients with DM, 18 with myositis with overlap, 8 with ASS, 27 with non-DM inflammatory myopathy (16 with polymyositis, 6 with inclusion body myositis, 5 with immune-mediated necrotizing myopathy), 8 with muscular dystrophy (4 with dysferlinopathy, 4 with fascioscapulohumeral muscle dystrophy) and 10 healthy controls. RESULTS: We found RIG-I-positive fibers in 50% of DM samples vs 11% in non-DM samples (p < 0.001). Interestingly, RIG-I staining identified 32% of DM patients without perifascicular atrophy (p = 0.007). RIG-I sensitivity was higher than perifascicular atrophy (p < 0.001). No differences in specificity between perifascicular atrophy and RIG-I staining were found (92% vs 88%). RIG-I staining was more reproducible than perifascicular atrophy (κ coefficient 0.52 vs 0.37). CONCLUSIONS: The perifascicular pattern of RIG-I expression supports the diagnosis of DM. Of importance for clinical and therapeutic studies, the inclusion of RIG-I in the routine pathological staining of samples in inflammatory myopathy will allow us to gather more homogeneous subgroups of patients in terms of immunopathogenesis.


Assuntos
Proteína DEAD-box 58/análise , Dermatomiosite/diagnóstico , Músculo Esquelético/patologia , Atrofia/patologia , Biomarcadores/análise , Diagnóstico Diferencial , Humanos , Miosite/diagnóstico
7.
J Transl Med ; 15(1): 29, 2017 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-28183315

RESUMO

BACKGROUND: Metabolic alterations play a role in the development of inflammatory myopathies (IMs). Herein, we have investigated through a multiplex assay whether proteins of energy metabolism could provide biomarkers of IMs. METHODS: A cohort of thirty-two muscle biopsies and forty plasma samples comprising polymyositis (PM), dermatomyositis (DM) and sporadic inclusion body myositis (sIBM) and control donors was interrogated with monoclonal antibodies against proteins of energy metabolism using reverse phase protein microarrays (RPPA). RESULTS: When compared to controls the expression of the proteins is not significantly affected in the muscle of PM patients. However, the expression of ß-actin is significantly increased in DM and sIBM in consistence with muscle and fiber regeneration. Concurrently, the expression of some proteins involved in glucose metabolism displayed a significant reduction in muscle of sIBM suggesting a repression of glycolytic metabolism in these patients. In contrasts to these findings, the expression of the glycolytic pyruvate kinase isoform M2 (PKM2) and of the mitochondrial ATPase Inhibitor Factor 1 (IF1) and Hsp60 were significantly augmented in DM when compared to other IMs in accordance with a metabolic shift prone to cancer development. PKM2 alone or in combination with other biomarkers allowed the discrimination of control and IMs with very high (>95%) sensitivity and specificity. Unfortunately, plasma levels of PKM2 were not significantly altered in DM patients to recommend its use as a non-invasive biomarker of the disease. CONCLUSIONS: Expression of proteins of energy metabolism in muscle enabled discrimination of patients with IMs. RPPA identified the glycolysis promoting PKM2 and IF1 proteins as specific biomarkers of dermatomyositis, providing a biochemical link of this IM with oncogenesis.


Assuntos
Carcinogênese/metabolismo , Dermatomiosite/metabolismo , Mitocôndrias/metabolismo , Proteínas/metabolismo , Piruvato Quinase/metabolismo , Anticorpos/metabolismo , Biomarcadores/metabolismo , Biópsia , Análise por Conglomerados , Metabolismo Energético , Humanos , Inflamação/diagnóstico , Inflamação/patologia , Músculos/metabolismo , Músculos/patologia , Análise Serial de Proteínas , Reprodutibilidade dos Testes , Frações Subcelulares/metabolismo
10.
Medicine (Baltimore) ; 95(8): e2368, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26937893

RESUMO

The extent of inflammatory infiltrates in arteries from patients with giant-cell arteritis (GCA) have been described using different terms and definitions. Studies investigating the relationship between GCA histological features and clinical manifestations have produced controversial results. The aims of this study were to characterize and validate histological patterns in temporal artery biopsies (TABs) from GCA patients, to explore additional histological features, including the coexistence of different patterns, and also to investigate the relationship of the inflammatory patterns with clinical and laboratory features.We performed histological examination of TAB from patients with GCA consecutively diagnosed between 1992 and 2012. Patterns of inflammation were defined according to the extent and distribution of inflammatory infiltrates within the artery. Clinical and laboratory variables were recorded. Two external investigators underwent a focused, one-day training session and then independently scored 77 cases. Quadratic-weighted kappa was calculated.TAB from 285 patients (200 female/85 male) were evaluated. Four histological inflammatory patterns were distinguished: 1 - adventitial (n = 16); 2 - adventitial invasive: adventitial involvement with some extension to the muscular layer (n = 21); 3 - concentric bilayer: adventitial and intimal involvement with media layer preservation (n = 52); and 4 - panarteritic (n = 196). Skip lesions were observed in 10% and coexistence of various patterns in 43%. Raw agreement of each external scorer with the gold-standard was 82% and 77% (55% and 46% agreement expected from chance); kappa = 0.82 (95% confidence interval [CI] 0.70-0.95) and 0.79 (95% CI 0.68-0.91). Although abnormalities on temporal artery palpation and the presence of jaw claudication and scalp tenderness tended to occur more frequently in patients with arteries depicting more extensive inflammation, no statistically significant correlations were found between histological patterns and clinical features or laboratory findings.In conclusion, we have described and validated 4 histological patterns. The presence of different coexisting patterns likely reflects sequential steps in the progression of inflammation and injury. No clear relationship was found between these patterns and clinical or laboratory findings. However, several cranial manifestations tended to occur more often in patients with temporal arteries exhibiting panarteritic inflammation. This validated score system may be useful to standardize stratification of histological severity for immunopathology biomarker studies or correlation with imaging.


Assuntos
Arterite de Células Gigantes/patologia , Artérias Temporais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Arterite de Células Gigantes/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes
11.
Addict Biol ; 21(1): 159-70, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25186090

RESUMO

In utero exposure of fetuses to tobacco is associated with reduced birth weight. We hypothesized that this may be due to the toxic effect of carbon monoxide (CO) from tobacco, which has previously been described to damage mitochondria in non-pregnant adult smokers. Maternal peripheral blood mononuclear cells (PBMCs), newborn cord blood mononuclear cells (CBMCs) and placenta were collected from 30 smoking pregnant women and their newborns and classified as moderate and severe smoking groups, and compared to a cohort of 21 non-smoking controls. A biomarker for tobacco consumption (cotinine) was assessed by ELISA (enzyme-linked immunosorbent assay). The following parameters were measured in all tissues: mitochondrial chain complex IV [cytochrome c oxidase (COX)] activity by spectrophotometry, mitochondrial DNA levels by reverse transcription polymerase chain reaction, oxidative stress by spectrophotometric lipid peroxide quantification, mitochondrial mass through citrate synthase spectrophotometric activity and apoptosis by Western blot parallelly confirmed by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) assay in placenta. Newborns from smoking pregnant women presented reduced birth weight by 10.75 percent. Materno-fetal mitochondrial and apoptotic PBMC and CBMC parameters showed altered and correlated values regarding COX activity, mitochondrial DNA, oxidative stress and apoptosis. Placenta partially compensated this dysfunction by increasing mitochondrial number; even so ratios of oxidative stress and apoptosis were increased. A CO-induced mitotoxic and apoptotic fingerprint is present in smoking pregnant women and their newborn, with a lack of filtering effect from the placenta. Tobacco consumption correlated with a reduction in birth weight and mitochondrial and apoptotic impairment, suggesting that both could be the cause of the reduced birth weight in smoking pregnant women.


Assuntos
Apoptose , Peso ao Nascer/fisiologia , DNA Mitocondrial/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Placenta/metabolismo , Fumar/metabolismo , Adulto , Western Blotting , Monóxido de Carbono , Estudos de Casos e Controles , Cotinina/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Marcação In Situ das Extremidades Cortadas , Recém-Nascido de Baixo Peso , Recém-Nascido , Leucócitos Mononucleares/metabolismo , Peróxidos Lipídicos/metabolismo , Masculino , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Espectrofotometria
12.
Autoimmun Rev ; 15(1): 9-15, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26299986

RESUMO

INTRODUCTION: Autoinflammatory diseases (AID) are usually diagnosed during the pediatric age. However, adult-onset disease or diagnosis during adulthood has been occasionally described. OBJECTIVES: To assess the clinical and genetic characteristics of adult patients diagnosed with an AID in an adult referral center for AID. METHODS: We retrospectively evaluated clinical and genetic features of adult patients (≥16 years) diagnosed with an AID or referred after AID diagnosis to the Clinical Unit of AID, at the Department of Autoimmune Diseases, Hospital Clínic of Barcelona, from 2008 to 2014. RESULTS: During the study period, a genetic study for suspected AID was requested to 90 patients at the Department of Autoimmune Diseases. A final diagnosis of monogenic AID was achieved in 17 patients (19% of patients tested). Five additional cases were diagnosed with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome and 10 patients with AID were referred from other adult departments. Finally, a total of 32 patients with AID were finally diagnosed or monitored in our Clinical Unit. These included 12 (37.5%) familial Mediterranean fever, 6 (18.8%) tumour necrosis factor-receptor associated periodic syndrome, 8 (25%) cryopirin-associated periodic syndromes (Muckle-Wells syndrome [MWS] or overlap familial cold-associated periodic syndrome/MWS), 1 (3.1%) mevalonate kinase deficiency, and 5 (15.6%) PFAPA. Clinical evidence of disease-onset during childhood and adulthood was observed in 15 (47%) and 17 (53%) patients, respectively. Overall, the final diagnosis was obtained after a delay of a mean of 12 years (range 0-47 years). Compared to children, adult patients with AID in our series presented more frequently with non-severe manifestations and none of them developed amyloidosis during follow-up. Adult patients also carried higher proportion of low-penetrance mutations or polymorphisms and all genetic variants were presented in heterozygosis or as heterozygous compounds. CONCLUSIONS: Adult disease-onset or delayed diagnosis of AID during adulthood is associated with milder disease phenotypes, and seem to be driven by mild genotypes, with predominant presence of low-penetrance mutations or polymorphisms.


Assuntos
Doenças Autoimunes/genética , Adulto , Genótipo , Humanos , Inflamação/genética , Inflamação/imunologia , Mutação , Seleção de Pacientes , Fenótipo
13.
FEM (Ed. impr.) ; 18(5): 331-335, sept.-oct. 2015. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-144625

RESUMO

INTRODUCCIÓN: Existen pocos estudios que de forma selectiva valoren la docencia clínica de una determinada asignatura. En este artículo se presenta la experiencia en docencia clínica de la asignatura 'Semiología General y Propedéutica Clínica' en tercer curso del Grado de Medicina en la Facultad de Medicina de la Universitat de Barcelona. MATERIALES Y MÉTODOS: Se han analizado los cursos 2011-2012, 2012-2013 y 2013-2014, representando un total de cinco 'cursos', ya que la asignatura es semestral y se imparte dos veces en cada curso académico. El período de docencia clínica de la asignatura es de siete semanas (28 días) y el número de alumnos oscila entre cuatro y ocho por cada una de las siete unidades/centros distintos. A su llegada se les informa de los objetivos de la estancia clínica y al final del período se les invita a cumplimentar una encuesta anónima y voluntaria en la que valoran distintos ítems. RESULTADOS: Se han recogido 477 encuestas (95%). Se constató una muy buena valoración global del período de docencia clínica (mediana: 5; primer cuartil: 4, en escala de 1 a 5), sin variaciones significativas entre los distintos períodos evaluados (p = 0,658). CONCLUSIONES. La docencia clínica en esta asignatura está muy bien valorada de forma global, sin detectar variaciones relevantes en los cinco cursos analizados


INTRODUCTION: There are very few studies regarding the clinical skills training of a particular matter. In the present study the experience in clinical training in the matter ‘Semiology and Clinical Propedeutics’ from the Faculty of Medicine in the University of Barcelona is presented. The results of surveys from five consecutive cycles are compared. MATERIALS AND METHODS: The period of study represents five cycles (2011-2014) since the matter is developed twice a year. The clinical period training in the matter spent seven weeks (28 days) and the number of students for each of the seven different facilities ranged from 4-8. When arriving, the students are informed about the objectives to be achieved through their training period, and at the end they are asked about the voluntary and anonymous survey complementation. RESULTS: A total of 95% (n = 477) of the requested surveys were collected. A very good global qualification was assessed (median: 5; first quartile: 4, in 1-5 scale), without significant differences among the different evaluated periods of time (p = 0.658). CONCLUSIONS: Clinical skills training in this matter is considered near excellent without significant variations through the five consecutive periods analyzed


Assuntos
Humanos , Ensino/organização & administração , Educação Médica/organização & administração , Docentes/organização & administração , Avaliação Educacional , Faculdades de Medicina/estatística & dados numéricos , Estudantes de Medicina/estatística & dados numéricos
15.
Rheumatol Int ; 35(5): 915-20, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25547622

RESUMO

The aim of the present study was to explore whether polymyositis may be considered as an isolated, organ-specific disease or more suitably as a secondary or associated entity. A retrospective re-evaluation of all the muscle biopsies performed at the Hospital Clínic of Barcelona showing histopathological pattern of polymyositis from January 1997 to May 2012 was carried out. The medical records of the patients with the aforementioned pathological pattern were also reviewed. From 1.290 muscle biopsies performed during the period evaluated, 36 with polymyositis pattern were identified. At the time of muscle biopsy, polymyositis pattern was secondary or associated with other disease in 26 patients and was classified as isolated in the remaining ten patients. After pathological re-evaluation and long-term clinical follow-up, only one patient remained with this diagnosis. Overall, the main final diagnosis related to the initial polymyositis pattern was inflammatory myopathy associated with connective tissue disease. Several other associated conditions were also identified. Isolated polymyositis is highly uncommon. Ruling out potential associated or confusing entities, like inclusion body myositis, overlap syndromes, infections, and cancer, is mandatory.


Assuntos
Doenças Autoimunes/complicações , Doenças do Tecido Conjuntivo/complicações , Músculo Esquelético/patologia , Neoplasias/complicações , Polimiosite/etiologia , Viroses/complicações , Adulto , Idoso , Doenças Autoimunes/diagnóstico , Estudos de Coortes , Doenças do Tecido Conjuntivo/diagnóstico , Bases de Dados Factuais , Diagnóstico Diferencial , Progressão da Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Miosite/diagnóstico , Miosite/etiologia , Miosite de Corpos de Inclusão/diagnóstico , Neoplasias/diagnóstico , Polimiosite/diagnóstico , Estudos Retrospectivos , Viroses/diagnóstico , Adulto Jovem
17.
Semin Arthritis Rheum ; 44(2): 228-33, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24830790

RESUMO

OBJECTIVES: Dermatomyositis (DM) constitutes a subset of idiopathic inflammatory myopathies clinically characterized by proximal muscle weakness and skin involvement. Some of the dermatologic manifestations are highly prevalent and characteristic, but others such as generalized or limb edema are truly rare. The aim of the present study was to describe five cases of edematous DM diagnosed at our institution and to perform a review of the literature, as well as identify clinical, laboratory, or pathological data associated with this manifestation. METHODS: We performed a retrospective clinical, laboratory, and pathological evaluation of five cases of this edematous presentation out of 86 DM cases diagnosed at our hospital from 2004 to 2013. Moreover, we undertook a medical literature search using inflammatory myopathy, dermatomyositis, and edema as key words, limited to articles published in MEDLINE, EMBASE, and LILACS database in English and Spanish from 1987 to 2013. RESULTS: A total of 19 patients were identified, five diagnosed at our hospital and 14 cases from the literature. Overall, the median time from disease onset to diagnosis was 2 months, and most of the patients (16/84 patients, 21%) required more aggressive therapy, including immunosuppressive agents and intravenous immunoglobulin (12/63 patients, 15%). Microinfarction was present 2.3 times more frequently in DM patients with edema compared with those without edema. CONCLUSIONS: The presence of edema in DM is uncommon but seems to be a sign of severe disease, requiring early and aggressive treatment. Microischemia-producing microinfarction may play an important pathophysiological role and determine the degree of disease severity.


Assuntos
Dermatomiosite/complicações , Dermatomiosite/diagnóstico , Edema/diagnóstico , Edema/etiologia , Dermatopatias/diagnóstico , Dermatopatias/etiologia , Idoso , Idoso de 80 Anos ou mais , Dermatomiosite/tratamento farmacológico , Edema/tratamento farmacológico , Evolução Fatal , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Retrospectivos , Índice de Gravidade de Doença , Dermatopatias/tratamento farmacológico , Resultado do Tratamento
18.
Ann Rheum Dis ; 73(7): 1388-92, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24665112

RESUMO

BACKGROUND: Positron emission tomography (PET) scan is emerging as a promising imaging technique to detect large-vessel inflammation in giant cell arteritis (GCA). However, the lack of a standardised definition of arteritis based on (18)fluorodeoxyglucose (FDG) uptake is an important limitation to the use of PET scan for diagnostic purposes. OBJECTIVE: To prospectively assess the intensity and distribution of FDG uptake at different vascular territories in patients with newly diagnosed GCA compared with controls. METHODS: 32 consecutive, biopsy-proven, GCA patients treated with glucocorticoids for ≤3 days were included. The control group consisted of 20 individuals, who underwent PET/CT for cancer staging. Maximal standardised uptake value (SUVm) was calculated at four aortic segments, supraaortic branches and iliac-femoral territory. Sensitivity and specificity was calculated by receiver-operator characteristic curves (ROC) analysis. RESULTS: Mean SUVm was significantly higher in patients than in controls in all vessels explored and correlated with acute-phase reactants and serum IL-6. Mean of the SUVm at all the vascular territories had an area under the curve (AUC) of 0.830, and a cut-off of 1.89 yielded a sensitivity of 80% and a specificity of 79% for GCA diagnosis. There were no significant differences in AUC among the vascular beds examined. CONCLUSIONS: FDG uptake by large vessels has a substantial sensitivity and specificity for GCA diagnosis.


Assuntos
Artérias/diagnóstico por imagem , Arterite de Células Gigantes/diagnóstico por imagem , Proteínas da Fase Aguda/imunologia , Idoso , Idoso de 80 Anos ou mais , Aorta/diagnóstico por imagem , Área Sob a Curva , Artérias/patologia , Artéria Axilar/diagnóstico por imagem , Biópsia , Artérias Carótidas/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Artéria Femoral/diagnóstico por imagem , Fluordesoxiglucose F18 , Arterite de Células Gigantes/imunologia , Arterite de Células Gigantes/patologia , Humanos , Artéria Ilíaca/diagnóstico por imagem , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Curva ROC , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Artéria Subclávia/diagnóstico por imagem , Artérias Temporais/patologia , Tomografia Computadorizada por Raios X
19.
Front Physiol ; 4: 393, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24427140

RESUMO

Phosphofructokinase deficiency is a very rare autosomal recessive disorder, which belongs to group of rare inborn errors of metabolism called glycogen storage disease. Here we report on a new mutation in the phosphofructokinase (PFK) gene PFKM identified in a 65-years-old woman who suffered from lifelong intermittent muscle weakness and painful spasms of random occurrence, episodic dark urines, and slight haemolytic anemia. After ruling out the most common causes of chronic haemolytic anemia, the study of a panel of 24 enzyme activities showed a markedly decreased PFK activity in red blood cells (RBCs) from the patient. DNA sequence analysis of the PFKM gene subsequently revealed a novel homozygous mutation: c.926A>G; p.Asp309Gly. This mutation is predicted to severely affect enzyme catalysis thereby accounting for the observed enzyme deficiency. This case represents a prime example of classical PFK deficiency and is the first reported case of this very rare red blood cell disorder in Spain.

20.
Ann Rheum Dis ; 72(9): 1481-7, 2013 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22993227

RESUMO

BACKGROUND: Interleukin 17A (IL-17A) exerts pivotal proinflammatory functions in chronic inflammatory and autoimmune diseases. OBJECTIVE: To investigate IL-17A expression in temporal artery lesions from patients with giant-cell arteritis (GCA), and its relationship with disease outcome. METHODS: Fifty-seven patients with biopsy-proven GCA were prospectively evaluated, treated and followed for 4.5 years (52-464 weeks). Relapses, time (weeks) required to achieve a maintenance prednisone dose <10 mg/day, and time (weeks) to complete prednisone withdrawal were prospectively recorded. IL-17A mRNA was measured by real-time quantitative RT-PCR in temporal arteries from all patients and 19 controls. IL-17 protein expression was assessed by immunohistochemistry/immunofluorescence. RESULTS: IL-17A expression was significantly increased in temporal artery samples from GCA patients compared with controls (6.22±8.61 vs 2.50±3.9 relative units, p=0.016). Surprisingly, patients with strong IL-17A expression tended to experience less relapses, and required significantly shorter treatment periods (median 25 vs 44 weeks to achieve <10 mg prednisone/day, p=0.0079). There was no correlation between IL-17A and RORc or RORα expression suggesting that these transcription factors may not exclusively reflect Th17 differentiation, and that cells other than Th17 cells might contribute to IL-17 expression in active patients. Accordingly, FoxP3(+)IL-17A(+) cells were identified in lesions by confocal microscopy and were dramatically reduced in specimens from treated patients. CONCLUSIONS: IL-17A expression is increased in GCA lesions, and is a predictor of response to glucocorticoid treatment. The contribution of FoxP3+ cells to IL-17A production in untreated patients suggests that induced-Tregs may facilitate disease remission when proinflammatory cytokine production is downregulated by glucocorticosteroids.


Assuntos
Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Interleucina-17/metabolismo , Prednisona/uso terapêutico , Artérias Temporais/patologia , Idoso , Idoso de 80 Anos ou mais , Regulação para Baixo/efeitos dos fármacos , Feminino , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Arterite de Células Gigantes/metabolismo , Arterite de Células Gigantes/patologia , Humanos , Interleucina-17/genética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Indução de Remissão , Linfócitos T Reguladores , Artérias Temporais/metabolismo , Resultado do Tratamento
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