Oxidative stress and vascular disease in patients with Systemic Lupus Erythematosus and prima Antiphospholipid Syndrome

Systemic Lupus Erythematosus (SLE) and the Antiphospholipid Syndrome (APS) are related autoimmune diseases, characterised by a broad spectrum of clinical features associated with autoantibodies directed towards nuclear and phospholipid / protein antigens, respectively. Accelerated atherosclerosis has been recognized as a major feature of both conditions, however the mechanisms by which it occurs are not clear. Oxidative stress is an important factor in atherosclerosis and the presence of an increased oxidative state has been recognized in SLE and APS. The overall aim of this thesis is to identify possible factors that contribute to this oxidative stress and to evaluate the mechanisms involved. Two different animal models were used to study the effects of anti-CL antibodies on nitric oxide (NO) synthesis. In a short term functional rat model (4 hours), a human anti-CL IgG monoclonal antibody (IS4) increased NO production through induction of iNOS, whilst in a long term mouse model (30 days), IS4 was associated with a pro-oxidant status with a decrease in paraoxonase activity (an anti-oxidant enzyme present in HDL) and nitric oxide levels, resulting in a decrease in total anti-oxidant capacity of plasma. Nitrotyrosine levels were increased suggesting a previous increased NO production, confirming the findings of the short-term model. In a clinical study, serum from patients with APS, presented an inverse correlation between anti-phospholipid antibodies and paraoxonase activity, confirming the results reported in the animal models. In patients with SLE, anti-HDL antibodies were identified and inversely correlated with paraoxonase activity and with total anti-oxidant capacity of plasma. These antibodies were shown to be a heterogeneous group, represented by antibodies cross-reacting with cardiolipin and antibodies directed against a different antigen, probably apolipoprotein A-I. In another clinical setting, infertile women submitted to in vitro fertilization, positive for anti-cardiolipin antibodies but without the Antiphospholipid Antibody Syndrome, presented with similar pro-oxidant changes in their serum, suggesting that these can be a direct consequence of the antibodies rather than an independent characteristic of the syndrome. In conclusion, anti-phospholipid antibodies may induce oxidative stress in patients with SLE and APS through a short-term up-regulation of nitric oxide synthesis, associated with an inhibition of the anti-oxidant activity of paraoxonase. In long-term, these effects combine to create a pro-oxidant environment, which can explain the enhance atherogenesis and thrombogenesis found in these patients

Biological Therapy in Systemic Sclerosis

Systemic sclerosis is the autoimmune connective tissue disease with the highest morbidity and mortality, through the combination of inflammation, vasculopathy and fibrosis leading to severe internal organ involvement. Currently, there are no approved disease-modifying therapies, and treatment is based on organ-specific treatment and broad immunosuppression, with disappointing long-term results in most cases. Recent research has helped to improve knowledge of the pathogenesis of systemic sclerosis and to optimize treatment based on specific physiopathological targets, and a new era of biological agents in systemic sclerosis has now begun. Promising results are emerging from targeting specific cytokine signalling, especially IL-6, and cellular subpopulations such as B cells, with anti-CD20 therapy, and T-cells, with inhibition of T-cell co-stimulation. Other approaches under evaluation are based on the modulation of profibrotic pathways by anti-TGF-β agents. In this chapter, we discuss the available evidence to support the use of each biological agent in systemic sclerosis based on data from basic and translational research and on results from clinical studies

implications for atherosclerosis and autoimmunity

Publisher Copyright: © 2021 John Wiley & Sons Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.Inflammation and immune dysfunction have been increasingly recognized as crucial mechanisms in atherogenesis. Modifications in cell lipid metabolism, plasma dyslipidaemia and particularly low high-density lipoprotein (HDL) levels occur both in atherosclerosis and in autoimmune rheumatic diseases (which are strongly associated with an increased risk of atherosclerosis), suggesting the presence of a crucial link. HDL, the plasma lipoprotein responsible for reverse cholesterol transport, is known for its several protective effects in the context of atherosclerosis. Among these, HDL immunomodulatory effects are possibly the less understood. Through the efflux of cholesterol from plasma cell membranes with the consequent disruption of lipid rafts and the interaction with the cholesterol transporters present in the plasma membrane, HDL affects both the innate and adaptive immune responses. Animal and human studies have demonstrated a predominance of HDL anti-inflammatory effects, despite some pro-inflammatory actions having also been reported. The HDL role on the modulation of the immune response is further suggested by the detection of low levels together with a dysfunctional HDL in patients with autoimmune diseases. Here, we review the current knowledge of the immune mechanisms of atherosclerosis and the modulatory effects HDL may have on them.publishersversionpublishe

Is the orthodontic smile considered as aesthetic in adult patients?

Distributed under Creative Commons Licence CC-BY 4.0In the last five years, pioneer studies were carried out in the Egas Moniz University Clinic surrounding the mental representation of the smile, centred on adolescent patients wearing orthodontic appliances, emerging with the results obtained as a new form of categorizing the perfect smile: The Orthodontic Smile. The present study is qualitative and exploratory and aims to understand the importance of the self-perception (mental representation) of the smile, now with the help of a new age range - Adult Patients. The sample consists of 100 subjects in the adult phase (25–59 y), namely patients wearing orthodontic appliances who were asked to draw two percepts about the self-perception of their own smile in two distinct moments: the first drawing, corresponding to before the wear of the orthodontic appliance (M1), and the second one, corresponding to drawing their smile after undergoing the orthodontic treatment (M2). The content analysis of the 200 drawings obtained was realized through a grid of content analysis, constituted by categories and subcategories. The patients also filled out a sociodemographic questionnaire, in which they responded to four open-ended questions in relation to the mental representation of the smile. Regarding the content analysis of the narrative, we highlight the fact that a Nice Smile seems to be mostly described as a Natural Smile and Aligned, being a motive for the seeking of dental treatment, primarily aesthetic issues, followed by functional considerations. When comparing the drawings before (M1) and after (M2) the wear of orthodontic appliances, the Category Broad Smile, is set up as the smile chosen as the most aesthetic. It seems that aesthetic motives represent the motivational power for the patient in the adult phase, when they decide to look for Orthodontic treatment.info:eu-repo/semantics/publishedVersio

X-ray vision: mental representation of adolescent’s oral cavity undergoing orthodontic treatment

Article licensed under a Creative Commons Attribution 4.0 International LicenseIntroduction: Oral Hygiene is notoriously relevant in the context of orthodontic treatment; however, oral health self-care is often considered inadequate.Objective: The objectives of this study focus on the perception of the inner oral cavity in patients and seek the enabling of Self-care through the empowerment of their knowledge.Materials and Methods: 25 subjects were asked to draw the interior of their oral cavity before (M1) and after (M2) going through orthodontic treatment. The percepts were then quoted using a content analysis grid of analytical categories and subcategories that was created especially for this study.Results and Conclusion: The results are suggesting that there are differences in the level of investment with a diminution in the representations of the inner oral cavity after the wear of orthodontic appliance. In addition to this, the initial directive was seemed to not be fully perceived by the subjects as most of the patients represented the inner oral cavity as an Extra-Oral configuration followed with a Frontal View Smile.info:eu-repo/semantics/publishedVersio

Studying Erythromelalgia Using Doppler Flowmetry Perfusion Signals and Wavelet Analysis—An Exploratory Study

Funding Information: This research was financed by national funds through FCT—Foundation for Science and Technology, I.P. (Portugal), under the [UIDB/04567/2020] and [UIDP/04567/2020] programs. All imaging instrumentation was provided by ALIES-COFAC. Publisher Copyright: © 2023 by the authors.Erythromelalgia (EM) is a rare disease, which is still poorly characterized. In the present paper, we compared the hand perfusion of one female EM patient, under challenges, with a healthy control group. Using a laser Doppler flowmeter (LDF) with an integrated thermal probe, measurements were taken in both hands at rest (Phase I) and after two separate challenges—post-occlusive hyperemia (PORH) in one arm (A) and reduction of skin temperature (cooling) with ice in one hand (B) (Phase II). The final measurement periods corresponded to recovery (Phases III and IV). The control group involved ten healthy women (27.3 ± 7.9 years old). A second set of measurements was taken in the EM patient one month after beginning a new therapeutic approach with beta-blockers (6.25 mg carvedilol twice daily). Z-scores of the patient’s LDF and temperature fluctuations compared to the control group were assessed using the Wavelet transform (WT) analysis. Here, fluctuations with |Z| > 1.96 were considered significantly different from healthy values, whereas positive or negative Z values indicated higher or lower deviations from the control mean values. Cooling elicited more measurable changes in LDF and temperature fluctuations, especially in higher frequency components (cardiac, respiratory, and myogenic), whereas PORH notably evoked changes in lower frequency components (myogenic, autonomic, and endothelial). No significant Z-score deviations were observed in the second measurement, which might signify a stabilization of the patient’s distal perfusion following the new therapeutic approach. This analysis involving one EM patient, while clearly exploratory, has shown significant deviations in WT-derived physiological components’ values in comparison with the healthy group, confirming the interest in using cold temperature as a challenger. The apparent agreement achieved with the clinical evaluation opens the possibility of expanding this approach to other patients and pathologies in vascular medicine.publishersversionpublishe

Extra-Cranial Involvement in Giant Cell Arteritis

Recent advances in imaging studies and treatment approaches have greatly improved our knowledge about Giant Cell Arteritis (GCA). Previously thought of as a predominantly cranial disease, we now know that GCA is a systemic disease that may involve other medium and large vessel territories. Several imaging studies have shown that between 30 and 70% of patients with GCA present with large-vessel vasculitis. Moreover, a significant proportion of patients present large-vessel disease in the absence of cranial involvement. Extra-cranial disease also poses management challenges as these patients may have a more refractory-relapsing disease course and need additional therapies. Aortic dilation and aneurysms are well-described late complications of GCA involving the large artery territories. In this chapter, we discuss the clinical picture of extra-cranial involvement in GCA, focusing on improved diagnostic protocols and suitable treatment strategies

Será o sorriso ortodôntico considerado estético em pacientes adultos?

Introdução: Foram efetuados estudos pioneiros nos últimos cinco anos, na Clínica Universitária Egas Moniz, sobre a representação mental da boca e do sorriso em pacientes adolescentes portadores de aparelho ortodôntico fixo. Nos referidos estudos, concluímos que, a partir da análise qualitativa dos resultados sobre a representação mental do sorriso, parece emergir uma nova forma de caracterizar o sorriso perfeito – O Sorriso Ortodôntico. Objetivos: Pretendemos com o presente estudo relevar a importância da autoperceção da boca e do sorriso, ao nível da representação mental de um sujeito adulto que recorre ao uso de aparelho ortodôntico fixo. O presente estudo de natureza qualitativa e exploratória tem como objetivo compreender, assim, a importância da autoperceção da boca e do sorriso ortodôntico em sujeitos adultos. Material e Métodos: A amostra do estudo é constituída por 80 sujeitos no estádio da adultícia (25-59anos) (OMS,2018), nomeadamente, sujeitos portadores de aparelho ortodôntico que foram convidados a efetuar dois desenhos do seu sorriso em dois momentos distintos: O primeiro desenho remete para o Momento antes do uso do aparelho ortodôntico (M1) e, no segundo desenho, o paciente é convidado a desenhar o seu sorriso após o uso do aparelho ortodôntico (M2). Resultados e Conclusões: Os resultados obtidos sugerem que, os principais motivos que levaram os pacientes a procurar cuidados dentários parecem estar mais conotados com problemas estéticos, nomeadamente, a busca por um sorriso alinhado e esteticamente harmonioso