174 research outputs found
The Role of Oxidative Stress in the Development of Systemic Sclerosis Related Vasculopathy
Get PDFSystemic sclerosis (SSc) is a rare connective tissue disease characterized by autoimmunity, vasculopathy, and progressive fibrosis typically affecting multiple organs including the skin. SSc often is a lethal disorder, because effective disease-modifying treatment still remains unavailable. Vasculopathy with endothelial dysfunction, perivascular infiltration of mononuclear cells, vascular wall remodeling and rarefaction of capillaries is the hallmark of the disease. Most patients present with vasospastic attacks of the digital arteries referred to as 'Raynaud's phenomenon,' which is often an indication of an underlying widespread vasculopathy. Although autoimmune responses and inflammation are both found to play an important role in the pathogenesis of this vasculopathy, no definite initiating factors have been identified. Recently, several studies have underlined the potential role of oxidative stress in the pathogenesis of SSc vasculopathy thereby proposing a new aspect in the pathogenesis of this disease. For instance, circulating levels of reactive oxygen species (ROS) related markers have been found to correlate with SSc vasculopathy, the formation of fibrosis and the production of autoantibodies. Excess ROS formation is well-known to lead to endothelial cell (EC) injury and vascular complications. Collectively, these findings suggest a potential role of ROS in the initiation and progression of SSc vasculopathy. In this review, we present the background of oxidative stress related processes (e.g., EC injury, autoimmunity, inflammation, and vascular wall remodeling) that may contribute to SSc vasculopathy. Finally, we describe the use of oxidative stress related read-outs as clinical biomarkers of disease activity and evaluate potential anti-oxidative strategies in SSc
Rapid free thiol rebound is a physiological response following cold-induced vasoconstriction in healthy humans, primary Raynaud and systemic sclerosis
Get PDFRaynaud's phenomenon (RP) is often the first sign of systemic sclerosis (SSc). Molecular mechanisms involved are incompletely understood, but reactive oxygen, nitrogen, and sulfur species are thought to play an important role in the pathogenesis of SSc. Free thiol groups play a protective role against oxidative stress and may represent an attractive therapeutic target. We aimed to investigate the effects of hypothermia-induced vasoconstriction on the responsiveness of redox-related markers. Thirty participants (n = 10/group [SSc, primary Raynaud's phenomenon (PRP), healthy controls (HC)]) were included in this study. Fingertip photoelectric plethysmography was performed during a standardized cooling and recovery experiment. Venous blood was collected at four predetermined time points. Free thiols, NO-derived species (nitros(yl)ated species, nitrite, nitrate), sulfate and endothelin-1 were measured. Lower baseline concentrations of free thiols were observed in PRP and SSc patients (HC: 5.87 [5.41-5.99] μmol/g; PRP: 5.17 [4.74-5.61]; SSc 5.28 [4.75-5.80], P = 0.04). Redox-related markers remained unchanged during cooling. However, an unexpected increase in systemic free thiol concentrations was observed in all groups during the recovery phase. The response of this marker differed between groups, with a higher increase found in SSc patients (HC Δ = 1.30 [1.48-1.17]; PRP Δ = 1.04 [1.06-1.03]; SSc Δ = 1.72 [1.13-1.49], P = 0.04). NO-derived species, sulfate and endothelin-1 levels remained unchanged throughout the recovery phase. This exploratory study sheds light on the rapid responsiveness of systemic free thiol concentrations following reperfusion, which may reflect overall redox balance. The robust response to reperfusion in SSc patients suggests that reductive systems involved in this response are functionally intact in these patients
Giving purpose to reclaimed interior building materials in the transformation of building 22 of TU DELFT: By the use of R-strategies Refuse, Reuse, Repair, Repurpose and Recycle
No full textThe building industry waste and transportation can be reduced by reclaiming building components. Building 22, Applied Physics on the Campus of TU Delft can be transformed into student housing and public functions by using reclaimed building components of the existing building, in order to achieve the environmental ambitions of the TU Delft and to strengthen the relationship with the city regarding. This research assesses the potential of various interior building components by means of R-strategies for the future functional needs. By distributing the building components amongst the five R-strategies, a basis for a vision of the future of this building can be derived. This case could be an example for reducing costs and be a road towards a more sustainable building industry.Architecture, Urbanism and Building Sciences | Architectural Engineerin
Scleroderma-like Pattern in Various Rheumatic Diseases reply
Get PDFWe thank Dr. Lambova for her interesting comment1 on our recent article published in The Journal2 We reported that a systemic sclerosis (SSc) or scleroderma-like capillaroscopic pattern is common in patients with Raynaud phenomenon, and can be frequently observed in patients with connective tissue diseases (CTD) other than SSc.</p
The sense of a beginning : Bakhtinian dialogic criticism on 'the gospel' in Mark.
Get PDFContemporary literary approaches have caused paradigm shifts in Biblical Studies in the last two decades as it appears in a great deal of Markan studies using narrative, reader-response, deconstructive, feminist, and new historicist approaches. However, literary studies on the Gospel of Mark have not taken into account theoretical questions underlying those approaches. As a result biblical critics are driven by new trends without ever having a chance to examine the critical baggage of the approaches. Consequently, there is a gap of communication between the old and the new one. Therefore this thesis is an attempt to meet the need of enhancing the quality of critical endeavour in biblical studies. In the light of most recent competing critical theories of literature, the first contribution of this thesis is the methodological finding that Bakhtinian dialogic criticism contains the most profound philosophical and practical foundations for solving some crucial theoretical problems in contemporary literary theories. It is a critique to a Saussurian linguistic system of language which becomes the very foundation of modern and postmodern literary criticism. Bakhtinian literary theory shifts the foundation of literary criticism on linguistic signs into the creative activity of the socio-cultural production of human communication. The shift into socio-cultural reality of language communication makes the notion of 'genre' very important to unlock the problem of text and context in literary studies. Since the Gospel of Mark has fascinated most literary critics in Biblical Studies, the problem of 'genre' of this gospel is chosen as the focus of this study. Secondly, as no agreement is reached as to what 'genre' the Gospel of Mark belongs, this thesis makes its contribution to the discussion by locating the problem of 'genre' of Mark in the context of genre theories and argues that the Bakhtinian suggestion to find genre in the socio-cultural sphere by analysing artistic intercourse between narrative agents in Mark has freed the competing analysis from the unresolved problem between the kerygmatic (content oriented) approach and the analogical (form oriented) approach. To achieve finding 'genre' in the socio-cultural sphere, this thesis focuses on Bakhtinian analysis of the process of artistic intercourse between narrative agents. The narrative communicative interrelationships between narrative agents is constructed in this thesis as a 'stereophonic' Bakhtinian model of dialogic communication. This model is an original contribution of this thesis for revising the traditional two dimensional model of narrative communication. Based on this dialogical model of communication, a special role is given to the Bakhtinian 'author-creator' in the realization process of genre through the interaction of polyphonic voices. Through the interaction of voices of the author-artist and the hero we are led to discover a relatively stable type of portraying and controlling reality in Mark, known as the genre of Roman 'satire'. The closest literary affinity is Satyrica by Petronius. This narrative strategy of 'satire' in Mark has its root in the prophetic discourse of the Old Testament which is saturating the speech of the narrator, John the Immerser, the centurion, the people, and even Jesus. Finally, the whole search for Markan 'genre' culminates in the analysis of the realization of genre through the analysis of Bakhtinian chronotope. The reality of the genre of Mark is its social reality that is in its role as dpxrj/ 'beginning'. As the Gospel of Mark proclaims itself as 'a beginning', it defines its claim of socio-cultural 'authority' in early Christianity. It is this 'sense of beginning' which enables the narrating and the narrated world of Mark to interact dialogically
Skin Autofluorescence Based Decision Tree in Detection of Impaired Glucose Tolerance and Diabetes
Get PDF<p>Aim: Diabetes (DM) and impaired glucose tolerance (IGT) detection are conventionally based on glycemic criteria. Skin autofluorescence (SAF) is a noninvasive proxy of tissue accumulation of advanced glycation endproducts (AGE) which are considered to be a carrier of glycometabolic memory. We compared SAF and a SAF-based decision tree (SAF-DM) with fasting plasma glucose (FPG) and HbA1c, and additionally with the Finnish Diabetes Risk Score (FINDRISC) questionnaire +/- FPG for detection of oral glucose tolerance test (OGTT)- or HbA1c-defined IGT and diabetes in intermediate risk persons.</p><p>Methods: Participants had >= 1 metabolic syndrome criteria. They underwent an OGTT, HbA1c, SAF and FINDRISC, in adition to SAF-DM which includes SAF, age, BMI, and conditional questions on DM family history, antihypertensives, renal or cardiovascular disease events (CVE).</p><p>Results: 218 persons, age 56 yr, 128M/90F, 97 with previous CVE, participated. With OGTT 28 had DM, 46 IGT, 41 impaired fasting glucose, 103 normal glucose tolerance. SAF alone revealed 23 false positives (FP), 34 false negatives (FN) (sensitivity (S) 68%; specificity (SP) 86%). With SAF-DM, FP were reduced to 18, FN to 16 (5 with DM) (S 82%; SP 89%). HbA1c scored 48 FP, 18 FN (S 80%; SP 75%). Using HbA1c-defined DM-IGT/suspicion >= 6%/42 mmol/mol, SAF-DM scored 33 FP, 24 FN (4 DM) (S76%; SP72%), FPG 29 FP, 41 FN (S71%; SP80%). FINDRISC >= 10 points as detection of HbA1c-based diabetes/suspicion scored 79 FP, 23 FN (S 69%; SP 45%).</p><p>Conclusion: SAF-DM is superior to FPG and non-inferior to HbA1c to detect diabetes/IGT in intermediate-risk persons. SAF-DM's value for diabetes/IGT screening is further supported by its established performance in predicting diabetic complications.</p>
Plasma Nitrate Levels Are Related to Metabolic Syndrome and Are Not Altered by Treatment with DPP-4 Inhibitor Linagliptin:A Randomised, Placebo-Controlled Trial in Patients with Early Type 2 Diabetes Mellitus
Get PDFThe depletion of nitrate and nitrite, stable nitric oxide (NO) end-products, promotes adipose tissue dysfunction and insulin resistance (IR). Dipeptidyl peptidase-4 (DPP-4) inhibitors have the potentially beneficial side effect of increasing NO availability. In this study, nitrate and nitrite levels and the effects of DPP-4 inhibitor linagliptin were investigated in relation to metabolic syndrome (MetS) markers. Treatment-naive patients with early type 2 diabetes mellitus (T2DM) (n = 40, median age 63 IQR (55-67) years, 63% male, mean HbA1c 45 ± 4.4 mmol/mol) were randomized (1:1) to linagliptin (5 mg/day) or placebo. MetS-related markers (body mass index (BMI), triglycerides, HOMA-IR, gamma-glutamyltransferase (GGT), C-reactive protein (CRP), and adiponectin), plasma levels of nitrate, nitrite, total free thiols (TFT) and vegetable intake were estimated at baseline and after 4 and 26 weeks of treatment. Plasma nitrate, but not nitrite, correlated positively with vegetable intake (r = 0.38, p = 0.018) and was inversely associated with HOMA-IR (r = -0.44, p = 0.006), BMI (r = -0.35, p = 0.028), GGT (r = -0.37, p = 0.019) and CRP (r = -0.34, p = 0.034). The relationship between nitrate and HOMA-IR remained significant after adjusting for BMI, CRP, vegetable intake and GGT. With stable vegetable intake, nitrate and nitrite, TFT, adipokines and CRP did not change after 26 weeks of linagliptin treatment. While plasma nitrate is inversely associated with MetS, linagliptin treatment does not significantly influence nitrate and nitrite concentrations, oxidative stress, adipose tissue function and systemic inflammation.</p
Abdominal pain in a man with an endovascular aortic prosthesis
Get PDFA 79-year-old man with an abdominal aorta aneurysm (AAA) with endovascular repair presented with abdominal pain and inflammation. Although the initial work-up was in favour of an idiopathic inflammatory AAA, FDG-PET imaging showed atypical irregular uptake. Per-operative assessment and culture of pus matter revealed infection by Listeria monocytogenes. Atypical findings on imaging of aortic wall inflammation should alarm the clinician of an infectious aetiology.</p
Skin autofluorescence is elevated in neovascular age-related macular degeneration
No full textBackground/aims Skin autofluorescence (AF) is a non-invasive marker for advanced glycation endproducts (AGE) in tissues, making use of their characteristic AF pattern. The aim of this study was to investigate whether skin AF is increased in patients with neovascular age-related macular degeneration (AMD) compared with healthy controls. Methods Skin AF was assessed in 73 consecutive patients with active and documented neovascular AMD without evidence for diabetic or hypertensive retinopathy and in 31 healthy age-matched controls. Exclusion criteria were: known renal disease, current inflammatory or malignant disease, or skin type V or VI. Skin AF was measured on the forearm and was calculated as a ratio of mean intensities detected from the skin between 420-600 and 300-420 nm. Student t test and chi(2) test were used to compare differences between groups. Results Skin AF was increased in neovascular AMD compared with controls (2.57+/-0.68 vs 2.23+/-0.63 arbitrary units x 10(-2); p=0.018). In patients without vascular risk factors or cardiovascular disease, skin AF was not significantly higher than that of the controls. Skin AF correlated with age in both patients and controls. Conclusion Skin AF is increased in patients with neovascular AMD, suggesting that AMD is accompanied by enhanced systemic AGE accumulation, which may indicate a role in the pathophysiology of AMD
Correction: Abdulle, A.E., et al. Hydrogen Sulfide: A Therapeutic Option in Systemic Sclerosis. Int. J. Mol. Sci. 2018, 19, 4121:A Therapeutic Option in Systemic Sclerosis (vol 19, 4121, 2018)
Get PDFThe authors wish to make the following correction to this paper [...].</p
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