BackgroundThe ischemia-reperfusion injury (IRI) is unavoidable in vascular surgery. Damage to the microcirculation and endothelial glycocalyx might set up a shock with loss of circulatory coherence and organ failure. Sulodexide may help to protect endothelial glycocalyx and alleviate the ischemia-reperfusion injury.MethodsTwenty female piglets underwent surgery with a 30-min-long suprarenal aortic clamp, followed by two hours of reperfusion. Ten piglets received sulodexide before the clamp, and 10 received normal saline. Blood and urine samples were taken at baseline and in 20-min intervals until the 120th minute to analyze the serum syndecan-1, E-selectin, and thrombomodulin. Albumin and glycosaminoglycans were examined in the urine. The kidney biopsies before and after the protocol were examined by light microscopy with hematoxylin-eosin staining. The sublingual microcirculation was recorded by side-stream dark field imaging at the time as blood and urine.ResultsBased on the 2-way ANOVA testing, there was no statistically significant difference in the parameters of sublingual microcirculation. Serum markers of endothelial cell activation and damage (E-selectin and thrombomodulin) did not show any statistically significant difference either. Syndecan-1, a marker of glycocalyx damage, showed statistically significantly higher values based on the 2-way ANOVA testing (p < 0.0001) with the highest difference in the 80th minute: 7.8 (3.9-44) ng/mL in the control group and 1.8 (0.67-2.8) ng/mL in the sulodexide group. In the urine, the albuminuria was higher in the control group, although not statistically significant. Glycosaminoglycans were statistically significantly higher in the sulodexide group based on the mixed-effect analysis due to the intervention itself. Histological analysis of the renal biopsies showed necrosis in both groups after reperfusion.ConclusionAdministering sulodexide significantly reduced the level of endothelial markers of IRI. The study results support further research into using preemptive administration of sulodexide to modulate IRI in clinical medicine.

• MeSH
• E-selektin krev   MeSH
• glykokalyx MeSH
• glykosaminoglykany * farmakologie   terapeutické užití   MeSH
• ledviny patologie   krevní zásobení   MeSH
• mikrocirkulace účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• prasata MeSH
• reperfuzní poškození * prevence a kontrola   MeSH
• syndekan-1 krev   MeSH
• trombomodulin krev   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

This paper describes the synthesis of a new A-homo lactam D-homo lactone androstane derivative from dehydroepiandrosterone. To evaluate the impact of the introduction of nitrogen in the parental scaffold on biological activity, a new androstane enamide-type lactam derivative was prepared and characterized. The new compound as well as starting compounds were screened for cytotoxic, anti-angiogenic and anti-inflammatory activities using several human cancer cell lines (MCF-7, MDA-MB-231, PC3, CEM, G-361, HeLa), endothelial (HUVEC) and non-tumour (MRC-5 and BJ) cell lines. Strong cytotoxic and anti-inflammatory activity with a broad therapeutical window was demonstrated by the A-homo lactam D-homo lactone androstane derivative. The induction of apoptosis in treated PC3 cultures was confirmed using apoptotic morphology screening and a fluorescent double-staining method. New A-homo lactam D-homo lactone androstane derivative induced apoptosis more than the tested reference compounds, Formestane and Doxorubicin. An in silico ADME analysis showed that the compounds possess drug-like properties.

• MeSH
• androstany chemie   izolace a purifikace   farmakologie   MeSH
• antiflogistika chemie   izolace a purifikace   farmakologie   MeSH
• apoptóza účinky léků   MeSH
• E-selektin antagonisté a inhibitory   biosyntéza   MeSH
• fytogenní protinádorové látky chemie   izolace a purifikace   farmakologie   MeSH
• kultivované buňky MeSH
• laktony chemie   izolace a purifikace   farmakologie   MeSH
• lidé MeSH
• molekulární konformace MeSH
• optické zobrazování MeSH
• proliferace buněk účinky léků   MeSH
• screeningové testy protinádorových léčiv MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Acute lymphoblastic leukemia (ALL) and its treatment are associated with endothelial dysfunction (ED) and increased cardiovascular risk in adulthood. There are no data on ED in children after successful treatment of ALL. We aimed to assess new ED in these children using the plethysmographic reactive hyperemia index (RHI) and biomarkers that are known to be related to ED. In all, 22 children (mean 15.6 years), after successful treatment of ALL, and 18 healthy subjects were included in this prospective study. RHI, plasma concentrations of asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP) and E-selectin were measured in all children. RHI values were significantly lower in ALL patients when compared with healthy controls (p<0.05). hsCRP was significantly increased in ALL patients compared with the control group (p<0.001). E-selectin plasma levels were higher in ALL patients as compared to healthy controls (p=0.05). This is the first study that combines both plethysmographic and biochemical methods to assess ED in ALL survivors. Significantly decreased RHI with elevated plasma concentrations of biochemical markers imply a possible association with premature ED in ALL patients. The combined diagnostic approach seems to be a valuable tool for more accurate detection of ED and preventive cardiovascular management in these patients.

• MeSH
• akutní lymfatická leukemie krev   diagnóza   patofyziologie   MeSH
• arginin analogy a deriváty   krev   MeSH
• biologické markery krev   MeSH
• C-reaktivní protein metabolismus   MeSH
• cévní endotel metabolismus   patofyziologie   MeSH
• dítě MeSH
• E-selektin krev   MeSH
• lidé MeSH
• mladiství MeSH
• nemoci cév krev   diagnóza   patofyziologie   MeSH
• pletysmografie metody   MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Psoriasis is a chronic systemic immune-mediated inflammatory dermatosis associated with several comorbidities. Psoriasis patients are at increased risk of developing cardiovascular diseases (CVD), namely, coronary heart disease, stroke or peripheral vascular disease, and psoriasis seems to be an independent cardiovascular risk factor. Antipsoriatic systemic therapy, especially anti-tumor necrosis factor (TNF)-α, seems to exert a beneficial effect on these comorbidities. The purpose of this study was: (i) to measure the level of cardiovascular serum markers in psoriasis patients in comparison with healthy volunteers; and (ii) to compare the serum level of the same markers in patients before and 3 months after adalimumab therapy. We investigated six biomarkers connected to CVD: C-reactive protein (measured high sensitively, hsCRP), oxidized low-density lipoproteins (oxLDL), oxLDL/β-glycoprotein I complex (oxLDL/β2GPI), vascular endothelial adhesion molecule 1 (VCAM-1), E-selectin and interleukin (IL)-22. These biomarkers were measured in 21 patients with moderate/severe psoriasis before and after treatment with adalimumab and in healthy volunteers. hsCRP (P < 0.05), oxLDL-β2GPI complex (P < 0.05), E-selectin (P < 0.001) and IL-22 (P < 0.001) were significantly increased in comparison with healthy controls, whereas oxLDL and VCAM-1 were also higher in psoriasis patients but the difference did not reach statistical significance. A decrease of E-selectin (P < 0.001) and IL-22 (P < 0.001) was observed after 3 months of adalimumab therapy. Inhibition of TNF-α seems to not only improve psoriasis but also decreases serum cardiovascular biomarkers. E-selectin and IL-22 could serve for monitoring of the efficacy of antipsoriatic systemic therapy on cardiovascular risk.

• MeSH
• adalimumab aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• beta-2-glykoprotein I krev   MeSH
• biologické markery krev   MeSH
• C-reaktivní protein analýza   MeSH
• cévní buněčněadhezivní molekula-1 krev   MeSH
• dermatologické látky aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• E-selektin krev   MeSH
• interleukiny krev   MeSH
• kardiovaskulární nemoci krev   komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoproteiny LDL krev   MeSH
• pilotní projekty MeSH
• psoriáza krev   komplikace   farmakoterapie   MeSH
• rizikové faktory MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

OBJECTIVE: This study investigates the associations of body mass index (BMI) and waist circumference (WC) with markers of systemic inflammation in midlife by race and gender. DESIGN: Data were obtained from the Survey of Midlife in the United States, a cross-sectional, observational study of Americans 35 years old or older (White men: N = 410; White women: N = 490; Black men: N = 58; Black women: N = 117). Inflammation was measured by concentrations of fibrinogen and C-reactive protein (CRP) in fasting plasma and concentrations of E-selectin and interleukin-6 (IL-6) in fasting serum. Anthropometric data were used to obtain BMI and WC. Socio-demographic and health-related factors were assessed with a survey. Multivariate models by race and gender were estimated to test the roles of BMI and WC for each inflammation marker. RESULTS: Compared to White men, Black women have higher BMI and higher levels of all four inflammation markers; White women have lower BMI, lower WC, and lower E-selectin and fibrinogen but higher CRP; and Black men have higher fibrinogen. After adjusting for socio-demographic and health-related covariates as well as perceived discrimination, WC is associated with all four markers of inflammation among White men and women; with three markers (fibrinogen, CRP, and IL-6) of inflammation among Black women; and with CRP (and marginally with fibrinogen and E-selectin) among Black men. BMI is associated with higher CRP and fibrinogen among Black men (marginally so for White men) but not for women of either race. CONCLUSIONS: WC shows more consistent associations with inflammation markers than BMI, although the relationships vary by inflammation marker and population group. Our findings suggest that WC is a risk factor for systemic inflammation among White and Black men and women, and BMI is an additional risk factor for Black men.

• MeSH
• běloši statistika a číselné údaje   MeSH
• biologické markery MeSH
• C-reaktivní protein biosyntéza   MeSH
• černoši nebo Afroameričané statistika a číselné údaje   MeSH
• dospělí MeSH
• E-selektin biosyntéza   MeSH
• fibrinogen biosyntéza   MeSH
• index tělesné hmotnosti * MeSH
• interleukin-6 biosyntéza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu MeSH
• obvod pasu * MeSH
• průřezové studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sexuální faktory MeSH
• socioekonomické faktory MeSH
• tělesné váhy a míry MeSH
• zánět etnologie   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Spojené státy americké MeSH

INTRODUCTION: This study investigates social determinants of systemic inflammation, focusing on race, SES, and perceived discrimination. METHODS: Data on 884 white and 170 black participants were obtained from the Survey of Midlife in the U.S., a cross-sectional observational study combining survey measures, anthropometry, and biomarker assay. Data, collected in 2004-2009, were analyzed in 2016. Main outcome measures were fasting blood concentrations of C-reactive protein, interleukin 6, fibrinogen, and E-selectin. For each biomarker, series of multivariate linear regression models were estimated for the pooled sample and separately for blacks and whites. Full models included social determinants; psychological, lifestyle, and health factors; and demographic covariates. RESULTS: Bivariate analyses indicated higher concentrations of all inflammation markers among blacks compared with whites (p<0.001). In fully adjusted models using the pooled sample, racial differences persisted for interleukin 6 (p<0.001) and fibrinogen (p<0.01). For E-selectin and C-reactive protein, racial differences were explained after adjusting for covariates. Education was linked to lower fibrinogen concentration (p<0.05) in the fully adjusted model and C-reactive protein concentration (p<0.01) after adjusting for demographic factors and income. Lifetime perceived discrimination was related to higher concentrations of fibrinogen (p<0.05) in the fully adjusted model, and higher concentrations of E-selectin and interleukin 6 (p<0.05) after adjusting for socioeconomic status (SES) and demographic factors. CONCLUSIONS: This study clarifies the contributions of race, SES, and perceived discrimination to inflammation. It suggests that inflammation-reducing interventions should focus on blacks and individuals facing socioeconomic disadvantages, especially low education.

• MeSH
• běloši psychologie   statistika a číselné údaje   MeSH
• biologické markery krev   MeSH
• C-reaktivní protein analýza   MeSH
• černoši nebo Afroameričané psychologie   statistika a číselné údaje   MeSH
• diskriminace (psychologie) MeSH
• disparity zdravotního stavu MeSH
• dospělí MeSH
• E-selektin krev   MeSH
• fibrinogen analýza   MeSH
• interleukin-6 krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• percepce MeSH
• průřezové studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sociální determinanty zdraví * MeSH
• společenská třída * MeSH
• zánět krev   epidemiologie   psychologie   MeSH
• zdravé chování MeSH
• životní styl MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

BACKGROUND: Little is known about the valve degeneration process after transcutaneous aortic valve implantations (TAVI) that can have an important impact on patients' long-term prognosis. AIM: To evaluate degenerative changes of TAVI using computed tomography (CT) compared to findings in patients that underwent surgical aortic valve replacement (SAVR). Subsequently, to compare the level of immune and inflammatory markers in both groups and test their possible role in the valve degeneration process. METHODS AND RESULTS: 49 patients after TAVI and 29 patients in the control group after SAVR underwent 2 years of follow-up and 8 patients from the TAVI group and 7 patients after SAVR underwent five years of follow-up. CT was performed in all patients and calcifications on prosthesis cusps in both groups were measured using Agatson calcium score. TAVI patients were older compared to patients who underwent SAVR [82 (62;86) vs. 74 (64;84) years, p<0.001], and had more comorbidities - higher EuroScore I [21.0 (5.0;46.0) vs. 6.15 (2.54;11.17), p<0.001]. TAVI patients had more often concomitant coronary artery disease (69.4% vs. 13.8%, p<0.001) and previous history of cardiac surgery (32.7% vs. 0.0%, p<0.001). Slight calcifications (mean Agatson score 50.76) on prosthetic cusps were found in 2 patients 4-5 years after TAVI and in 1 patient 2 years after SAVR (p=NS). Even though significant differences were found in values of tumor necrosis factor-α and E-selectin before, 1 year, and 2 years after implantation, no significant changes in values of inflammatory markers were observed during follow-up period in both groups of patients. Detailed analysis revealed no significant difference between values of inflammatory markers of patients with and without calcifications present on CT. CONCLUSION: Minimal degenerative changes on TAVI prosthesis were observed in mid- and long-term follow-up. Systemic immune response did not differ between patients after TAVI and SAVR.

• MeSH
• aortální chlopeň diagnostické zobrazování   chirurgie   MeSH
• aortální stenóza chirurgie   MeSH
• biologické markery krev   MeSH
• C-reaktivní protein analýza   MeSH
• chirurgická náhrada chlopně metody   MeSH
• cytokiny krev   MeSH
• E-selektin krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• multidetektorová počítačová tomografie MeSH
• následné studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• transkatetrální implantace aortální chlopně * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

• MeSH
• adalimumab aplikace a dávkování   farmakologie   MeSH
• biologické markery krev   MeSH
• C-reaktivní protein analýza   MeSH
• E-selektin krev   MeSH
• hodnocení rizik MeSH
• kardiovaskulární nemoci epidemiologie   etiologie   MeSH
• lidé MeSH
• pilotní projekty MeSH
• psoriáza * farmakoterapie   MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

Double balloon enteroscopy (DBE) was introduced 15 years ago. The complications of diagnostic DBE are rare, acute pancreatitis is most redoubtable one (incidence about 0.3%). Hyperamylasemia after DBE seems to be a rather common condition respectively. The most probable cause seems to be a mechanical straining of the pancreas. We tried to identify patients in a higher risk of acute pancreatitis after DBE. We investigated several laboratory markers before and after DBE (serum cathepsin B, lactoferrin, E-selectin, SPINK 1, procalcitonin, S100 proteins, alfa-1-antitrypsin, hs-CRP, malondialdehyde, serum and urine amylase and serum lipase). Serum amylase and lipase rose significantly with the maximum 4 hours after DBE. Serum cathepsin and procalcitonin decreased significantly 4 hours after DBE compared to healthy controls and patients values before DBE. Either serum amylase or lipase 4 hours after DBE did not correlate with any markers before DBE. There was a trend for an association between the number of push-and-pull cycles and procalcitonin and urine amylase 4 hours after DBE; between procalcitonin and alfa-1-antitrypsin, cathepsin and hs-CRP; and between E-selectin and malondialdehyde 4 hours after DBE. We found no laboratory markers determinative in advance those patients in a higher risk of acute pancreatitis after DBE.

• MeSH
• akutní nemoc MeSH
• alfa-1-antitrypsin krev   MeSH
• amylasy krev   moč   MeSH
• biologické markery krev   moč   MeSH
• C-reaktivní protein metabolismus   MeSH
• dvojbalonová enteroskopie škodlivé účinky   MeSH
• E-selektin krev   MeSH
• hyperamylazemie krev   etiologie   MeSH
• kalcitonin krev   MeSH
• kathepsiny krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipasa krev   MeSH
• malondialdehyd krev   MeSH
• pankreatitida krev   etiologie   MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Tumor cells interact with blood constituents and these interactions promote metastasis. Selectins are vascular receptors facilitating interactions of tumor cells with platelets, leukocytes, and endothelium, but the role of endothelial E-selectin remains unclear. Here we show that E-selectin is a major receptor for monocyte recruitment to tumor cell-activated endothelium. Experimental and spontaneous lung metastasis using murine tumor cells, without E-selectin ligands, were attenuated in E-selectin-deficient mice. Tumor cell-derived CCL2 promoted endothelial activation, resulting in enhanced endothelial E-selectin expression. The recruitment of inflammatory monocytes to metastasizing tumor cells was dependent on the local endothelial activation and the presence of E-selectin. Monocytes promoted transendothelial migration of tumor cells through the induction of E-selectin-dependent endothelial retractions and a subsequent modulation of tight junctions through dephosphorylation of VE-cadherin. Thus, endothelial E-selectin shapes the tumor microenvironment through the recruitment, adhesion, and activation of monocytes that facilitate tumor cell extravasation and thereby metastasis. These findings provide evidence that endothelial E-selectin is a novel factor contributing to endothelial retraction required for efficient lung metastasis. Cancer Res; 76(18); 5302-12. ©2016 AACR.

• MeSH
• CD antigeny metabolismus   MeSH
• cévní endotel metabolismus   MeSH
• E-selektin metabolismus   MeSH
• endoteliální buňky metabolismus   MeSH
• imunoblotting MeSH
• imunoprecipitace MeSH
• invazivní růst nádoru patologie   MeSH
• kadheriny metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• monocyty metabolismus   MeSH
• mutantní kmeny myší MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• polymerázová řetězová reakce MeSH
• průtoková cytometrie MeSH
• těsný spoj metabolismus   patologie   MeSH
• transendoteliální a transepiteliální migrace fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH