The Complex Management of the Breast Angiosarcoma: A Retrospective Study.

BACKGROUND/AIM: Breast angiosarcoma is a rare and aggressive disease with a poor prognosis. Two subtypes have been identified: primary angiosarcoma (PBA) and secondary breast angiosarcoma (SBA). In this retrospective analysis, we describe and compare our institute experience with the data existing in the literature. MATERIALS AND METHODS: We included in our analysis 29 patients who received a diagnosis of PBA or SBA between 2006 and 2019. RESULTS: All patients received surgery as frontline treatment, but only 6 patients underwent to adjuvant treatment. Neoadjuvant chemotherapy was administered 2 patients. The preferred chemotherapeutic regimen was taxanes with or without gemcitabine and associated with anthracyclines. A lower median RFS and OS were reported in patients with PBA compared to those with SBA, but the difference observed was not statistically significant. Patients with PBA had a lower median age at the diagnosis (38 vs. 75). CONCLUSION: In our analysis, we have shown a lower median RFS and OS in patients with PBA compared with those with SBA, and a significantly younger age at diagnosis in patients affected by PBA.

Elevated plasma levels of epithelial and endothelial cell markers in COVID-19 survivors with reduced lung diffusing capacity six months after hospital discharge.

BACKGROUND: Some COVID-19 survivors present lung function abnormalities during follow-up, particularly reduced carbon monoxide lung diffusing capacity (DLCO). To investigate risk factors and underlying pathophysiology, we compared the clinical characteristics and levels of circulating pulmonary epithelial and endothelial markers in COVID-19 survivors with normal or reduced DLCO 6 months after discharge. METHODS: Prospective, observational study. Clinical characteristics during hospitalization, and spirometry, DLCO and plasma levels of epithelial (surfactant protein (SP) A (SP-A), SP-D, Club cell secretory protein-16 (CC16) and secretory leukocyte protease inhibitor (SLPI)), and endothelial (soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and Angiopoietin-2) 6 months after hospital discharge were determined in 215 COVID-19 survivors. RESULTS: DLCO was < 80% ref. in 125 (58%) of patients, who were older, more frequently smokers, had hypertension, suffered more severe COVID-19 during hospitalization and refer persistent dyspnoea 6 months after discharge. Multivariate regression analysis showed that age ≥ 60 years and severity score of the acute episode ≥ 6 were independent risk factors of reduced DLCO 6 months after discharge. Levels of epithelial (SP-A, SP-D and SLPI) and endothelial (sICAM-1 and angiopoietin-2) markers were higher in patients with reduced DLCO, particularly in those with DLCO ≤ 50% ref. Circulating SP-A levels were associated with the occurrence of acute respiratory distress syndrome (ARDS), organizing pneumonia and pulmonary embolisms during hospitalization. CONCLUSIONS: Reduced DLCO is common in COVID-19 survivors 6 months after hospital discharge, especially in those older than 60 years with very severe acute disease. In these individuals, elevated levels of epithelial and endothelial markers suggest persistent lung damage.

The association between zinc and endothelial adhesion molecules ICAMs and VCAM-1 and nuclear receptors PPAR-ɑ and PPAR-γ: A systematic review on cell culture, animal and human studies.

BACKGROUND: Cardiovascular health is strongly influenced by diet. The levels of inflammatory factors like ICAM-1 and VCAM-1 are high in patients with atherosclerosis or predisposing factor for heart disease. Antioxidant and anti-inflammatory functions are attributed to zinc. We systematically reviewed cell culture, human or animal studies for determining the relationship between zinc status and ICAMs or VCAM-1 levels. METHODS: PubMed, Google Scholar, Scopus, and Cochrane databases from database inception till 30th August 2020 were systematically searched to obtain any possible article for inclusion. RESULTS: After screening and removing unrelated or duplicate articles by the title and abstract by two independent reviewers, 15 articles were included. Results indicating an inverse relationship between zinc status with ICAM-1 or VCAM-1 levels and the development of endothelial inflammation, plaque formation, or atherosclerosis. A direct relationship between zinc status and PPAR-α or γ levels was also observed. Zinc oxide (ZnO), zinc nanoparticles, or ions can cause endothelial activation and increased levels of ICAM-1 and VCAM-1. CONCLUSION: Normal function of the endothelium is linked with zinc level. Zinc deficiency causes atherosclerosis, most probably via increased production of ICAM-1 and VCAM-1; and decreased expression of PPAR-ɑ and PPAR-γ receptors. Contrarily, endothelial activation and increased ICAM-1 and VCAM-1 levels can be caused by ZnO, zinc nanoparticles, or zinc ions.

Free p-cresyl sulfate shows the highest association with cardiovascular outcome in chronic kidney disease.

BACKGROUND: Several protein-bound uraemic toxins (PBUTs) have been associated with cardiovascular (CV) and all-cause mortality in chronic kidney disease (CKD) but the degree to which this is the case per individual PBUT and the pathophysiological mechanism have only partially been unraveled. METHODS: We compared the prognostic value of both total and free concentrations of five PBUTs [p-cresyl sulfate (pCS), p-cresyl glucuronide, indoxyl sulfate, indole acetic acid and hippuric acid] in a cohort of 523 patients with non-dialysis CKD Stages G1-G5. Patients were followed prospectively for the occurrence of a fatal or non-fatal CV event as the primary endpoint and a number of other major complications as secondary endpoints. In addition, association with and the prognostic value of nine markers of endothelial activation/damage was compared. RESULTS: After a median follow-up of 5.5 years, 149 patients developed the primary endpoint. In multivariate Cox regression models adjusted for age, sex, systolic blood pressure, diabetes mellitus and estimated glomerular filtration rate, and corrected for multiple testing, only free pCS was associated with the primary endpoint {hazard ratio [HR]1.39 [95% confidence interval (CI) 1.14-1.71]; P = 0.0014}. Free pCS also correlated with a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (r = -0.114, P < 0.05), angiopoietin-2 (ANGPT2) (r = 0.194, P < 0.001), matrix metallopeptidase 7 (MMP-7; (r = 0.238, P < 0.001) and syndecan 1 (r = 0.235, P < 0.001). Of these markers of endothelial activation/damage, ANGPT2 [HR 1.46 (95% CI 1.25-1.70); P < 0.0001] and MMP-7 [HR 1.31 (95% CI 1.08-1.59); P = 0.0056] were also predictive of the primary outcome. CONCLUSIONS: Among PBUTs, free pCS shows the highest association with CV outcome in non-dialysed patients with CKD. Two markers of endothelial activation/damage that were significantly correlated with free pCS, ANGPT2 and MMP-7 were also associated with CV outcome. The hypothesis that free pCS exerts its CV toxic effects by an adverse effect on endothelial function deserves further exploration.

High-throughput identification of small molecules that affect human embryonic vascular development.

Birth defects, which are in part caused by exposure to environmental chemicals and pharmaceutical drugs, affect 1 in every 33 babies born in the United States each year. The current standard to screen drugs that affect embryonic development is based on prenatal animal testing; however, this approach yields low-throughput and limited mechanistic information regarding the biological pathways and potential adverse consequences in humans. To develop a screening platform for molecules that affect human embryonic development based on endothelial cells (ECs) derived from human pluripotent stem cells, we differentiated human pluripotent stem cells into embryonic ECs and induced their maturation under arterial flow conditions. These cells were then used to screen compounds that specifically affect embryonic vasculature. Using this platform, we have identified two compounds that have higher inhibitory effect in embryonic than postnatal ECs. One of them was fluphenazine (an antipsychotic), which inhibits calmodulin kinase II. The other compound was pyrrolopyrimidine (an antiinflammatory agent), which inhibits vascular endothelial growth factor receptor 2 (VEGFR2), decreases EC viability, induces an inflammatory response, and disrupts preformed vascular networks. The vascular effect of the pyrrolopyrimidine was further validated in prenatal vs. adult mouse ECs and in embryonic and adult zebrafish. We developed a platform based on human pluripotent stem cell-derived ECs for drug screening, which may open new avenues of research for the study and modulation of embryonic vasculature.

A conceptual time window-based model for the early stratification of trauma patients.

Progress in the testing of therapies targeting the immune response following trauma, a leading cause of morbidity and mortality worldwide, has been slow. We propose that the design of interventional trials in trauma would benefit from a scheme or platform that could support the identification and implementation of prognostic strategies for patient stratification. Here, we propose a stratification scheme based on defined time periods or windows following the traumatic event. This 'time-window' model allows for the incorporation of prognostic variables ranging from circulating biomarkers and clinical data to patient-specific information such as gene variants to predict adverse short- or long-term outcomes. A number of circulating biomarkers, including cell injury markers and damage-associated molecular patterns (DAMPs), and inflammatory mediators have been shown to correlate with adverse outcomes after trauma. Likewise, several single nucleotide polymorphisms (SNPs) associate with complications or death in trauma patients. This review summarizes the status of our understanding of the prognostic value of these classes of variables in predicting outcomes in trauma patients. Strategies for the incorporation of these prognostic variables into schemes designed to stratify trauma patients, such as our time-window model, are also discussed.

Arterial stiffness is not increased in patients with short duration rheumatoid arthritis and ankylosing spondylitis.

Patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have increased cardiovascular (CV) morbidity and mortality. Arterial stiffness is an independent predictor of CV events. The aim of the study was to assess arterial stiffness and inflammatory markers in patients with short duration chronic arthritis. We assessed carotid-femoral pulse wave velocity (PWV), augmentation index (AIx), traditional CV risk factors and inflammatory and endothelial markers in 71 chronic arthritis patients (RA and AS) and in 29 healthy controls. We did not find differences in PWV (for RA, AS and controls, respectively: 10 [8.8-10.9] versus 10.7 [9.1-11.8] versus 9.2 [8.3-11.4] m/s; p = .14) and AIx (for RA, AS and controls, respectively: 24.3 ± 11.5 versus 5.7 ± 12.4 versus 10 ± 12.8%; p = .22). Both groups of arthritis patients had active disease with significantly elevated inflammatory markers compared to controls. There were no correlations between endothelial and inflammatory markers and parameters of arterial stiffness in arthritis patients. When analyzing arthritis patients according to median of PVW, there were no significant differences in inflammatory and endothelial markers. We found that in patients with short duration active RA and AS arterial stiffness was not increased and furthermore, there was no association between markers of systemic inflammation and arterial stiffness.

Inhibition of breast tumor growth and abnormal angiogenesis in mice treated with endothelial cells and their progenitor mesenchymal stem cells derived from bone marrow.

Incorporation of endothelial cells or their progenitor cells into newly sprouting blood vessels can contribute to tissue vascularization after ischemic injury. However, the interaction of the stem cells-derived endothelial cells with angiogenesis within tumors is not well understood. The aim of this study was to examine the efficiency of endothelial-like cells derived from MSCs in controlling breast tumor growth associated with abnormal angiogenesis. For this purpose, Balb/c mouse model of breast carcinoma was developed and subjected to intra tumor (I.T)/intra venous (I.V) therapy with undifferentiated MSCs or endothelial cells derived from them. The homing of the stem cells was approved by measuring different markers as well as tracing green fluorescence protein (GFP)-labeled MSCs in the tumors. Tumor growth was measured following cell therapy using a digital caliper. At the end of treatment period (30 days) the angiogenesis markers; VEGFR2 expression as well as micro-vessel density (MVD) using CD31 were estimated in tumor tissues. Stem cell transplantation to mice bearing breast tumors resulted in tumor growth suppression in all experimental groups. The endothelial markers; CD31 and VEGFR2 were down regulated following I.T delivery of the endothelial cells. Accordingly, angiogenesis was suppressed following I.T administration of endothelial cells which was associated with increased focal necrosis in the tumors. In conclusion, data show that endothelial cells directly injected into tumors is more efficient compared to undifferentiated MSCs in controlling tumor-associated angiogenesis and tumor growth.

Differentiation of C57/BL6 mice bone marrow mononuclear cells into early endothelial progenitors cells in different culture conditions.

Endothelial progenitor cells (EPCs) can be isolated from bone marrow and characterized by the expression of cellular markers such as CD34, CD133, VEGFR2, CD31, and VE-Cadherin, by the uptake of acetylated low-density lipoprotein and by in vitro tube formation in tridimensional matrices. These cells are able to differentiate into mature endothelial cells and participate in the re-endothelization of damaged vessels. In this work, we tested different cultured media that can promote the proliferation and differentiation of mononuclear cells (MNCs) into early EPCs, with defined concentrations of growth factors and serum in order to establish a composition that may ensure us the reproducibility of our cultures. MNCs from mice bone marrow were cultivated using selective culture media containing DMEM or M199 supplemented with 10% FBS, VEGF, bFGF, and IGF, for 3, 7, and 14 days. Differentiation into early EPCs was analyzed using immunohistochemistry, FACS and western blotting and by functional parameters as uptake of ac-LDL, and formation of vessel-like structures. The cells cultivated with medium DMEM-M1 (DMEM plus VEGF, bFGF and IGF) expressed CD34, CD133, CD31, VEGFR2, and VE-Cadherin at all culture time-points with increased expression of these markers after 7 days. Only EPCs cultured for 30 days were able to form vessel-like structure. The uptake of ac-LDL was observed after 3, 7, 14, and 30 days, confirming the differentiation of mononuclear cells into early EPCs. DMEM-M1 was able to sustain MNCs proliferation and differentiation, increasing the expression of the characteristic EPC markers, allowing the expansion of early EPCs in culture in a similar way to that observed in commercial available media.

Endothelial markers are associated with thrombolysis resistance in acute stroke patients.

BACKGROUND AND PURPOSE: The endothelium is crucial in maintaining the haemostatic balance between pro- and anti-thrombotic factors. In this pilot study, the association of endothelial biomarkers with arterial recanalization and clinical outcome in the setting of acute ischaemic stroke (AIS) was evaluated amongst patients treated with recombinant tissue plasminogen activator (rt-PA). METHODS: Sixty-four AIS patients treated with rt-PA were prospectively recruited. Blood was collected before thrombolysis and analysed for von Willebrand factor (vWF), soluble thrombomodulin (sTM) and soluble endothelial protein C receptor (sEPCR). Complete recanalization was defined by a Thrombolysis in Myocardial Infarction Score of 3. Favourable clinical outcome was defined by a modified Rankin Score of 0-2 at 90 days. RESULTS: Amongst the 64 patients, 31 had no documented occlusion, 19 had persistent occlusion and 14 had complete recanalization. After adjustment for confounding factors, these patients presented lower sTM and sEPCR levels than patients with persistent occlusion (median sTM, 21 vs. 48 ng/ml, P = 0.008; median sEPCR, 78 vs. 114 ng/ml, P = 0.018), but similar levels compared with patients without occlusion. vWF levels did not differ between groups. None of these biomarkers was significantly associated with favourable outcome. CONCLUSIONS: Recanalization after thrombolytic therapy is associated with low sTM and sEPCR levels but not with vWF levels. If corroborated in further larger studies, these findings could be helpful in the identification of patients resistant to rt-PA thrombolysis who could benefit from a modified recanalization therapy.

Determining the association of inflammatory markers, cell-adhesion molecules, and endothelial dysfunction biomarkers with ACS in Indian population.

The observational study aims to evaluate inflammatory markers, cell adhesion molecules (CAM) and endothelial dysfunction markers as biomarkers in Indian ACS patients with no conventional risk factors. The study population included 110 healthy individuals and 102 ACS patients without any history of conventional risk factors, except smoking and alcoholism, were included. Patient history, biochemical parameters and levels of biomarkers were estimated. ACS patients had a significant elevation in the circulatory levels of biomarkers, such as IL-6, TNF-α, MCP1, MMP9, VCAM1, ICAM1 and E-selectin. CAM, inflammatory and endothelial biomarkers could help devise strategies for early, effective treatment of ACS.

Sex differences in childhood maltreatment, inflammation, and adulthood depression: A network analysis.

Background: Efforts to improve treatment for adults with major depression (MD) and childhood maltreatment (CM) have identified inflammation as a potential target to improve health. Network models have emerged as a new way to understand the relationship between depressive symptoms and inflammation. However, none have accounted for the role of childhood maltreatment in the link between depressive symptoms and inflammation, or sex differences commonly found in these constructs. Methods: Data from two waves of the Midlife Development in the United States study were used in this study (N = 1917). The Center for Epidemiological Studies Depression (CES-D) scale and Childhood Trauma Questionnaire, and six inflammation markers served as nodes in an undirected psychometric network analysis. Edges between nodes were calculated using partial Spearman's correlation. Separate networks were modeled for males and females. Results: The total network revealed several associations between nodes of CM, MD, and inflammation, with emotional abuse having a strong association with somatic complaints. Network comparison testing revealed male-female network invariance, with several edge differences between male and female networks. Males and females showed differences in associations across inflammatory markers and depressive symptom clusters, particularly among somatic complaints and interpersonal difficulties. Conclusions: Specific associations between dimensions of inflammation, CM, and MD may represent important targets for treatment. Network models disaggregated by sex showed that males and females may have fundamentally different associations between these constructs, suggesting that future studies should consider sex-specific interventions.

Spheroids of adipose derived stem cells show their potential in differentiating towards the angiogenic lineage.

INTRODUCTION: Adipose derived stem cells (ASCs) are a mesenchymal stem cell population of great scientific interest due to their abundance and easiness in obtaining them from adipose tissue. Recently, several techniques for three dimensional (3D) ASCs cultivation have been developed to obtain spheroids of adipose stem cells (SASCs). It was already proved that ASCs are able to differentiate towards the endothelial lineage thus, for the first time, we investigated the ability of our 3D SASCs to differentiate endothelially and the effects of not differentiated SASC secreted factors on specific cultured cells. MATERIALS AND METHODS: SASCs were differentiated with a specific medium towards endothelial lineage. Cell viability, gene and protein expression of typical endothelial markers were analysed. Moreover, tube formation, wound healing and migration assays were performed to investigate the ability in migration and angiogenic networks formation of endothelially differentiated cells. SASCs secretome were also tested. RESULTS: We showed the ability of SASCs to differentiate towards the endothelial lineage with an increase in cell viability of 15-fold and 8-fold at 14 and 21 days of differentiation respectively. Moreover, we showed the upregulation of VEGF-A and CD31 mRNAs of 9-fold and 1300-fold in SASCs endothelially differentiated cells, whilst protein expression was different. VEGF-A protein expression was upregulated whilst CD31 protein wasn't translated. In addition, ICAM1, VCAM1, ANGPT1, CD62E protein levels remain unchanged. SASCs were also able to organize themselves into angiogenic networks after 7 days of culturing themon ECMatrix. Secreted factors from undifferentiated 3D SASCs acted in a paracrine way on HUVECs and endothelially differentiated ASCs seeded on ECMatrix to promote angiogenic events. CONCLUSIONS: SASCs, thanks to their multilineage differentiation potential, also possess the ability to differentiate towards endothelial lineage and to organize themselves into angiogenic networks. Moreover, they are able to promote angiogenesis through their secreted factors.

Protective and therapeutic effectiveness of taurine supplementation plus low calorie diet on metabolic parameters and endothelial markers in patients with diabetes mellitus: a randomized, clinical trial.

BACKGROUND: Taurine supplementation as a sulfur-containing amino acid may attenuate and/or alleviate diabetes-induced complications and endothelial dysfunction via its anti-inflammatory and antioxidant activities. Our purpose was to investigate the effect of Taurine supplementation on endothelial dysfunction markers, oxidative stress, inflammation, and glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: In the current clinical trial, 120 patients with T2DM were randomly allocated to take either Taurine (containing 1 g Taurine, n = 60) or placebo (n = 60) three times per day for an eight-week period. Moreover, all patients were on a low-calorie diet. The primary outcome was fasting blood glucose (FBG) and endothelial markers including sera intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule (VCAM), and matrix metallopeptidase 9 (MMP-9). The secondary outcome was dietary intake, anthropometric indices, serum insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), total antioxidant capacity (TAC), tumor necrosis factor (TNF), high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and lipid profile. RESULTS: After 8 weeks, Taurine-supplemented patients had a considerable decrease in serum insulin and HOMA-IR compared to placebo group. However, Taurine supplementation did not improve other metabolic parameters including lipid profiles, glycated hemoglobin, and fasting blood glucose (FBG). There was a significant decline in MDA, TNF, and hs-CRP levels after these eight-week period of Taurine supplementation. In addition, the Taurine group had fewer serum levels of endothelial dysfunction markers than the placebo group. CONCLUSIONS: The evidence from our study revealed that Taurine supplementation significantly reduced insulin and HOMA-IR, as well as oxidative stress, inflammation, and endothelial markers in individuals with T2DM. Trial registration The protocol of the study was recorded in the Iranian Registry of Clinical Trials (IRCT20180712040438N3).

The Need for Individualized Risk Assessment in Cardiovascular Disease.

Cardiovascular disease remains the leading cause of death in the era of modern medicine despite major advancements in this field. Current available clinical surrogate markers and blood tests do not adequately predict individual risk of cardiovascular disease. A more precise and sophisticated tool that can reliably predict the thrombosis and bleeding risks at an individual level is required in order for clinicians to confidently recommend early interventions with a favorable risk-benefit profile. Critical to the development of this tool is the assessment and understanding of Virchow's triad and its complex interactions between hypercoagulability, endothelial dysfunction and vessel flow, a fundamental concept to the development of thrombosis. This review explores the pathophysiology of cardiovascular disease stemming from the triad of factors and how individualized risk assessment can be improved through the multimodal use of tools such as global coagulation assays, endothelial biomarkers and vessel flow assessment.

Histochemical Staining of Vasculogenic Mimicry.

Vasculogenic mimicry (VM) describes a new tumor microvascular paradigm of non-endothelial cells, where aggressive cancer cells independent of angiogenesis acquire the ability to fluid-conducting vessels. VM shows worse 5-year overall survival in cancer that suggesting that VM could be a promising surgical and effective adjuvant therapy strategy in prognostics of metastatic cancer patients. The current chapter is a comprehensive review on "Main Staining Methods and Protocols in Vasculogenic Mimicry." Here, we provide most up-to-date and detailed information upon microscopy and histology protocols for the identification and understanding of VM process in both in vitro and in vivo.

Quantitative Methods to Assess Adipose Vasculature.

Adipose tissue depots are invested with an extensive capillary network that is closely associated with maintenance of adipose functions and enables healthy tissue expansion. The capillary network displays a high level of plasticity, demonstrating either growth (angiogenesis) or regression (rarefaction) under various physiological/pathological conditions, which has significant consequences for cardiometabolic health. Thus, the visualization and quantification of adipose vascular networks is an important aspect of studying factors that regulate adipose tissue health. This chapter provides an overview of several methods to quantify adipose vascularization. In-depth protocols are provided for the visualization of vascular structures by staining and imaging of whole-mount adipose tissues or paraffin-embedded adipose tissue sections, together with the quantitative analysis of vascularization from these images.

Myocardial perfusion reserve in patients with chronic hepatitis C before and after direct-acting antiviral treatment-a pilot study.

INTRODUCTION: Patients with chronic hepatitis C (CHC) have an increased risk of atherosclerotic cardiovascular disease which may be due to inflammation and endothelial dysfunction caused by the chronic infection. In this prospective pilot study, we assessed, for the first time among patients with CHC the myocardial perfusion reserve (MPR) by Rubidium-82 (82 Rb) positron emission tomography (PET)/computed tomography (CT) before and after direct-acting antiviral (DAA) treatment and compared them with biomarkers of systemic inflammation and endothelial dysfunction. METHODS: We included 10 patients with CHC who received 8 or 12 weeks of DAA treatment. To obtain the MPR, a cardiac 82 Rb PET/CT scan at rest and adenosine-induced stress was performed at baseline and between 12 and 24 weeks post DAA treatment. Additionally, markers of endothelial dysfunction and inflammation were measured at baseline and 12 weeks after DAA treatment. RESULTS: All 10 patients achieved cure and the median age was 50 (range: 40-62 years). The median MPR before treatment was 3.1 (range: 2.3-4.8) compared to 2.9 (range: 2.2-4.1) after DAA treatment p = 0.63. Also, cure after DAA treatment was not associated with an overall significant decrease in markers of endothelial dysfunction and inflammation. DISCUSSION: Cure after DAA treatment in patients with CHC did not improve coronary microvascular function nor did it lead to a decrease in soluble markers of cardiovascular risk in the given time frame where the patients were followed. It should be noted, that MPR before DAA treatment was in the normal range. Considering the small sample size and short follow-up time, further studies are warranted to determine if viral clearance has an effect on coronary microvascular function and endothelial dysfunction.

Evaluation of Vascular Endothelial Function in Children with Type 1 Diabetes Mellitus.

Diabetic kidney disease belongs to the major complications of diabetes mellitus. Here, hyperglycaemia is a key metabolic factor that causes endothelial dysfunction and vascular changes within the renal glomerulus. The aim of the present study was to assess the function of the vascular endothelium in children with type 1 diabetes mellitus (type 1 diabetes) by measuring selected endothelial lesion markers in blood serum. The selected markers of endothelial lesions (sVCAM-1, sICAM-1, sE-SELECTIN, PAI-1, ADMA and RAGE) were assayed by the immunoenzymatic ELISA method. The study involved 66 patients (age: 5-18 years) with type 1 diabetes and 21 healthy controls (age: 5-16 years). In the type 1 diabetes patients, significantly higher concentrations of all of the assayed markers were observed compared to the healthy controls (p < 0.001). All of the evaluated markers positively correlated with the disease duration, the age, and BMI of the patients, while only PAI-1 and sE-SELECTIN were characteristic of linear correlations with the estimated glomerular filtration rate (eGFR). It can be concluded that endothelial inflammatory disease occurs in the early stages of type 1 diabetes mellitus in children. The correlations between PAI-1, sE-SELECTIN, and eGFR suggest an advantage of these markers over other markers of endothelial dysfunction as prognostic factors for kidney dysfunction in children with type 1 diabetes.