The effect of chronic cigarette smoking on microvascular function, insulin resistance and inflammatory state

Cigarette smoking, a major risk factor for cardiovascular disease, can induce proinflammatory state and endothelial injury - the earliest manifestations of atherosclerotic changes. The aim of the study was to assess cutaneous vascular reactivity, insulin resistance and circulating levels of inflammatory cytokines in 20 healthy habitual smokers and 24 healthy non-smokers. The groups were matched for age. We used laser Doppler imaging with iontophoretic application of 1% acethylcholine solution and local heating 44 °C on the dorsum of the palm. Serum monocyte chemotactic protein-1, tumour necrosis factor-alpha and interleukin-6 were measured by xMAP technology. Insulin resdistance was assessed by HOMA-IR method. Local heating-induced neurally-mediated and endotheliumdependent vasodilatation was significantly decreased in elderly smokers vs. elderly non-smokers (p < 0.05). Young smokers showed significantly reduced endothelium-dependent vasodilatation vs. young non-smokers (p < 0.05). Ach-induced vasodilatation was significantly decreased in the elderly smokers and elderly non-smokers groups vs. young smokers and young non-smokers groups (p < 0.05). The level of tumour necrosis factor-alpha was significantly higher in both groups of smokers vs. non-smokers (p < 0.05). The level of monocyte chemotactic protein-1 was slightly higher in smokers. Only the elderly smokers group exhibited a tendency to higher values of HOMA-IR. Data showed that long-lasting cigarette smoking significantly impairs peripheral microvascular function due to increased inflammatory response.publishersversionPeer reviewe

Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study

Centre for Genomic Pathogen Surveillance and the Euro-GASP study group: Sonja Pleininger, Alexander Indra, Irith De Baetselier, Wim Vanden Berghe, Blaženka Hunjak, Tatjana Nemeth Blažić, Panayiota Maikanti-Charalambous, Despo Pieridou, Hana Zákoucká, Helena Žemličková, Steen Hoffmann, Susan Cowan, Lasse Jessen Schwartz, Rita Peetso, Jevgenia Epstein, Jelena Viktorova, Ndeindo Ndeikoundam, Beatrice Bercot, Cécile Bébéar, Florence Lot, Susanne Buder, Klaus Jansen, Vivi Miriagou, Georgios Rigakos, Vasilios Raftopoulos, Eszter Balla, Mária Dudás, Lena Rós Ásmundsdóttir, Guðrún Sigmundsdóttir, Guðrún Svanborg Hauksdóttir, Thorolfur Gudnason, Aoife Colgan, Brendan Crowley, Sinéad Saab, Paola Stefanelli, Anna Carannante, Patrizia Parodi, Gatis Pakarna, Raina Nikiforova, Antra Bormane, Elina Dimina, Monique Perrin, Tamir Abdelrahman, Joël Mossong, Jean-Claude Schmit, Friedrich Mühlschlegel, Christopher Barbara, Francesca Mifsud, Alje Van Dam, Birgit Van Benthem, Maartje Visser, Ineke Linde, Hilde Kløvstad, Dominique Caugant, Beata Młynarczyk-Bonikowska, Jacinta Azevedo, Maria-José Borrego, Marina Lurdes Ramos Nascimento, Peter Pavlik, Irena Klavs, Andreja Murnik, Samo Jeverica, Tanja Kustec, Julio Vázquez Moreno, Asuncion Diaz, Raquel Abad, Inga Velicko, Magnus Unemo, Helen Fifer, Jill Shepherd, Lynsey PattersonBackground: Genomic surveillance using quality-assured whole-genome sequencing (WGS) together with epidemiological and antimicrobial resistance (AMR) data is essential to characterise the circulating Neisseria gonorrhoeae lineages and their association to patient groups (defined by demographic and epidemiological factors). In 2013, the European gonococcal population was characterised genomically for the first time. We describe the European gonococcal population in 2018 and identify emerging or vanishing lineages associated with AMR and epidemiological characteristics of patients, to elucidate recent changes in AMR and gonorrhoea epidemiology in Europe. Methods: We did WGS on 2375 gonococcal isolates from 2018 (mainly Sept 1-Nov 30) in 26 EU and EEA countries. Molecular typing and AMR determinants were extracted from quality-checked genomic data. Association analyses identified links between genomic lineages, AMR, and epidemiological data. Findings: Azithromycin-resistant N gonorrhoeae (8·0% [191/2375] in 2018) is rising in Europe due to the introduction or emergence and subsequent expansion of a novel N gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup, G12302 (132 [5·6%] of 2375; N gonorrhoeae sequence typing for antimicrobial resistance [NG-STAR] clonal complex [CC]168/63), carrying a mosaic mtrR promoter and mtrD sequence and found in 24 countries in 2018. CC63 was associated with pharyngeal infections in men who have sex with men. Susceptibility to ceftriaxone and cefixime is increasing, as the resistance-associated lineage, NG-MAST G1407 (51 [2·1%] of 2375), is progressively vanishing since 2009-10. Interpretation: Enhanced gonococcal AMR surveillance is imperative worldwide. WGS, linked to epidemiological and AMR data, is essential to elucidate the dynamics in gonorrhoea epidemiology and gonococcal populations as well as to predict AMR. When feasible, WGS should supplement the national and international AMR surveillance programmes to elucidate AMR changes over time. In the EU and EEA, increasing low-level azithromycin resistance could threaten the recommended ceftriaxone-azithromycin dual therapy, and an evidence-based clinical azithromycin resistance breakpoint is needed. Nevertheless, increasing ceftriaxone susceptibility, declining cefixime resistance, and absence of known resistance mutations for new treatments (zoliflodacin, gepotidacin) are promising.This study was supported by the European Centre for Disease Prevention and Control, the Centre for Genomic Pathogen Surveillance, the Li Ka Shing Foundation (Big Data Institute, University of Oxford), the Wellcome Genome Campus, the Foundation for Medical Research at Örebro University Hospital, and grants from Wellcome (098051 and 099202). LSB was funded by Conselleria de Sanitat Universal i Salut Pública, Generalitat Valenciana (Plan GenT CDEI-06/20-B), Valencia, Spain, and Ministry of Science, Innovation and Universities (PID2020–120113RA-I00), Spain, at the time of analysing and writing this manuscript.info:eu-repo/semantics/publishedVersio

Serum concentrations of cytokines and adhesion molecules as markers of endothelial dysfunction

Citokīnu un adhēzijas molekulu koncentrācijas serumā kā endotēlija disfunkcijas pakāpes rādītāji Anotācija Pētījuma mērķis ir novērtēt, kuru ar endotēlija šūnu funkcijām saistīto molekulu koncentrācijas serumā ir pārliecinošākie endotēlija šūnu funkcionālā stāvokļa rādītāji, kā arī noteikt atšķirīgām endoteliālās disfunkcijas attīstības stadijām raksturīgās izmaiņas. Materiāls ietver 234 personas ar plašu endoteliālās funkcijas variabilitāti. Tika noteikta endotēlija vazodilatējošā atbilde uz acetilholīna, siltuma un postokluzīvās cērpjošās asinsplūsmas stimuliem, kā arī ar endotēlija funkcijām saistītu molekulu seruma koncentrācijas. Rezultāti liecina, ka endotēlija šūnu vazodilatējošo aktivitāte pozitīvi korelē ar adiponektīna, IL-10 un IL-4, bet negatīvi – ar sEselektīna, sICAM-1, TNFα un VEGF koncentrācijām, kā arī vairākas būtiskas rādītāju atšķirības četrās atšķirīgas endotēlija disfunkcijas pakāpes pārstāvošajās pētījuma grupās. Atslēgas vārdi: endotēlija disfunkcija, insulīna rezistence, vazodilatācijas testi, adhēzijas molekulas, adiponektīnsSerum concentrations of cytokines and adhesion molecules as markers of endothelial dysfunction Abstract The aim of this study is to select the serum markers that are most convincing for detection of endothelial function as well as to select the markers characteristic for varied degrees of endothelial dysfunction. The study material includes 234 persons with wide variablilty of endothelial dysfunction. The vasodilatory response of endothelium was detected by acetylcholine-, heat- and post-occlusive shear stress-induced vasodilatation tests and serum concentrations of molecular markers associated with endothelial function was detected. The study results show positive correlations of vasodilatory function with adiponectin, IL-10 and IL-4, and negative correlations with sE-selectin, sICAM-1, TNFα and VEGF concentrations as well as several significant differences between the four study groups representing varied degrees of endothelial dysfunction. Key words: endothelial dysfunction, insulin resistance, vasodilatation tests, adhesion molecules, adiponecti

Relation of endothelial dysfunction and adipokines levels to insulin resistance in metabolic syndrome patients

Funding Information: The work was supported by the National Research Programme in Medicine 2006–2009, project No. 8, “Modern approaches in early diagnostics, prevention and treatment of diabetes mellitus and obesity-caused diseases”. This study was supported by grant No. 07-VP-8 from the Latvian Council of Science.Obese metabolic syndrome (MS) patients were categorised into three groups: 44 with type 2 diabetes mellitus (T2DM)(D); 20 with T2DM and coronary artery disease (CAD) (DC), and 26 with MS alone (M). Eighteen healthy subjects were selected as controls (C). Insulin resistance (IR) was assessed by HOMA-IR. Adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) concentrations were measured by xMAP technology. Endothelin-1 (ET-1) was determined by ELISA. We used laser Doppler imaging for evaluating cutaneous endothelium-dependent vasodilatation in the hand. D and DC groups had significantly elevated IR compared with M or C group (P < 0.01). TNF-α, IL-6, IL-8, MCP-1 and ET-1 levels in DC were significantly elevated compared with other groups (P < 0.001). IL-6, IL-8, MCP-1 and ET-1 in D group were higher than those in C group (P < 0.05). TNF-α, IL-6, IL-8, MCP-1 and ET-1 concentrations were correlated with HOMA-IR indexes and adiponectin levels. All patients had lower adiponectin concentrations than controls (P < 0.001), but there were no differences between the patient groups. Only D and DC groups demonstrated a significant and similar decrease in LDI-Ach marker compared to C group (P < 0.001). LDI-Ach values were significantly correlated with HOMA-IR indexes and adiponectin levels (P < 0.001). Our findings show that obese MS patients have significantly increased HOMA-IR, TNF-α, IL-6, MCP-1 and IL-8 levels, decreased adiponectin concentration, and endothelial dysfunction, but the presence of T2DM and CAD in these patients is associated with more pronounced endothelial dysfunction and increased production of inflammatory cytokines and chemokines.publishersversionPeer reviewe

Neopterin, cellular adhesion molecules and myeolperoxidase in patients with stable and unstable angina pectoris

Recent data indicate that the serum level of neopterin, a marker of inflammation and immune modulator secreted by monocytes/macrophages, is elevated in patients with acute coronary syndrome (ACS) and seems to be a prognostic marker for major cardiovascular events. Soluble cellular adhesion molecules (sCAMs) and myeloperoxidase (MPO) levels are also related to ACS. The aim of the present study was to evaluate differences in serum levels of neopterin, sCAMs and MPO between coronary artery disease and metabolic syndrome (CAD-MetS) patients with stable and unstable angina pectoris (SAP, UAP), and to clarify the relationships between neopterin and other biomarkers. The study included 60 patients with CAD-MetS who were classified into two groups, 30 patients with SAP and 30 patients with UAP. Twenty healthy subjects were selected as controls (C). Serum soluble vascular cell adhesion molecule-1 (sVCAM-1), intercellular cell adhesion molecule-1 (sICAM-1), sE-selectin and MPO levels were measured by Luminex xMAP technology, and serum neopterin concentrations were measured by radioimmunoassay. Results: Serum levels of neopterin, MPO, sVCAM-1, sICAM-1, and sE-selectin were significantly higher in patients with UAP in comparison with the group of healthy controls (P < 0.05). Patients with SAP also had higher levels of these biomarkers than those in healthy controls (P < 0.05), except for sE-selectin. The biomarker level did not differ between the two patient groups, except for MPO, which was significantly higher in the USP group (P < 0.05). Neopterin was significantly correlated only with sVCAM-1 (P < 0.05). In conclusion, CAD-Met patients with SAP had more apparent raised levels of serum sICAM-1 and sVCAM-1, simultaneously with higher MPO and neopterin concentrations, in comparison to those in healthy subjects. However, UAP is also associated with more substantial changes in MPO and significantly increased sE-selectin levels. Neopterin concentration was had a close correlation only with sVCAM-1.publishersversionPeer reviewe