Platelet-Derived Drug Targets and Biomarkers of Ischemic Stroke-The First Dynamic Human LC-MS Proteomic Study.

(1) Objective: The aim of this dynamic LC-MS (liquid chromatography and mass spectrometry) human platelet proteomic study was to identify the potential proteins candidates for biomarkers of acute ischemic stroke (AIS), their changes during the acute phase of stroke and to define potential novel drug targets. (2) Methods: A total of 32 patients (18-80 years old) were investigated that presented symptoms of AIS lasting less than 24 h from the onset, confirmed by neurological examination and/or new cerebral ischemia visualized in the CT (computed-tomography) scans. The analysis of platelet proteome was performed using LC-MS at baseline, and then on the third and seventh day from the onset of symptoms. The control group was demographically matched without any clinical signs of acute brain injury. (3) Results: The differences between platelets, at 24 h after first symptoms of stroke subjects and the control group included: ß-amyloid A4 and amyloid-like protein 2, coactosin-like protein, thymidine phosphorylase 4 (TYMP-4), interferon regulatory factor 7 (IRF7), vitamin K-dependent protein S, histone proteins (H2A type 1 and 1-A, H2A types 2B and J, H2Av, -z, and -x), and platelet basic protein. The dynamic changes in the platelet protein concentration involved thrombospondin-1, thrombospondin-2, filamin A, B, and C. (4) Conclusions: This is the first human dynamic LC-MS proteomic study that differentiates platelet proteome in the acute phase of ischemic stroke in time series and compares the results with healthy controls. Identified proteins may be considered as future markers of ischemic stroke or therapeutic drug targets. Thymidine phosphorylase 4 (TYMP-4) holds promise as an interesting drug target in the management or prevention of ischemic stroke.

Effect of the Renin-Angiotensin-Aldosterone System Reactivity on Endothelial Function and Modulative Role of Valsartan in Male Subjects with Essential Hypertension.

BACKGROUND: The aim of the study was to evaluate the relationship between renin-angiotensin-aldosterone (RAA) system activity and reactivity, and the endothelial function profile in normotensive subjects (N), and in essential hypertensives (H), followed by analysis of the modulatory role of an angiotensin receptor blocker (ARB): valsartan, administered in the management of hypertension. METHODS: A total of 101 male subjects were enrolled to the study: 31H and 70N. The nitric-oxide (NO) bioavailability (l-Arginine, asymmetric dimethylarginine (ADMA)), symmetric dimethylarginine (SDMA), endothelial vasodilative function (flow mediated dilation (FMD)), oxidative-stress markers (malonyldialdehyde (MDA), thiol index (GSH/GSSG), nitrotyrozine (N-Tyr)), and pro-inflammatory/angiogenic parameters (sICAM-1, sVCAM-1, PAI-1, sE-selectin, PAI-1, thromboxane -B2) were assessed at baseline, then after intravenous -l-arginine administration, which was repeated after the 4-day acetylsalicylic acid (ASA) administration (75 mg/24 h). In hypertensives, this whole protocol was repeated following 2 weeks of valsartan therapy. RESULTS: No effect of valsartan and ASA on the flow-mediated vasodilation (FMD) and the NO bioavailability in hypertensives was observed. Administration of valsartan increased plasma renin activity (PRA), but without a decrease in the aldosterone levels. ASA treatment minimized the pre-existing differences between the groups, and increased the PRA in the N-subgroup with the highest ARR values. The blood concentrations of proinflammatory sICAM-1, sE-selectin, sVCAM-1, and PAI-1 were higher, whereas the anti-inflammatory 6-keto-PGF1 alpha level was lower in hypertensive subjects. The levels of angiogenic VEGF did not differ between groups. CONCLUSIONS: Our study does not confirm the modulative effect of valsartan on endothelial function. Normotensive men showed an increase in FMD after l-arginine administration, possibly indicating baseline impairment of the NO synthesis.

Cardiovascular risk factors and the concentration of asymmetric dimethylarginine.

BACKGROUND: The most commonly recognized cardiovascular risk factors (CVRF) include smoking cigarettes, manifestation of arterial hypertension (AH), hypercholesterolemia, hypertriglyceridemia, manifestation of type 2 diabetes mellitus (DM), and the presence of overweight or obesity. In recent years, investigations have documented the significance of asymmetric dimethylarginine concentration (ADMA) in the pathogenesis of diseases affecting the cardiovascular system. OBJECTIVES: To evaluate the relationship between the number of CVRF and blood ADMA concentration. MATERIAL AND METHODS: The study was conducted on a sample of 138 individuals (mean age 54.90 ±10.38 years). Among the participants, we distniguished subgroups with no CVRF (group A, n = 21), with 1-2 CVRF (group B, n = 53), with 3-4 CVRF (group C, n = 55), and with 5-6 CVRF (group D, n = 9). Plasma concentrations of arginine and of endogenous methylarginines were estimated. RESULTS: Plasma ADMA concentrations proved to be significantly higher in groups B, C and D than those in group A. Regression analysis allowed us to demonstrate that in the studied population of patients, manifestation of type 2 DM, followed by AH and hypercholesterolemia, were linked to the highest probability of elevated plasma ADMA concentration. CONCLUSIONS: Higher concentration of ADMA in the blood may be a marker for higher cardiovascular risk, especially associated with hypertension, type 2 DM and hypercholesterolemia.

Endothelial Function in Children with Acute Lymphoblastic Leukemia (ALL) May Reflect the Clinical Outcome.

Endothelial dysfunction is a common feature of early complications of hemato-oncologic therapy. The aim of our study was to assess the profile of endothelial function at diagnosis time, then during initial treatment phase of acute lymphoblastic leukemia (ALL), and to verify the presence of its correlation with early clinical outcome (ECO). 28 ALL children and 18 healthy age-matched control ones were recruited. Study group was examined at baseline and at 33rd and 78th day of treatment. At each protocol step the endothelial function was assessed by measurement of sP-selectin (CD62-P), PAI-1(serpinE1), sE-selectin (CD62E), sICAM-1(sCD54), sVCAM-1(sCD106), and VEGF concentrations. Higher baseline sICAM-1 and sVCAM-1 levels and lower sP-selectin and VEGF were observed in children with ALL. sICAM-1, sVCAM-1, and sE-selectin levels were decreasing following the treatment with protocol I. Higher sE-selectin and lower baseline sICAM-1 levels were observed in children treated unsuccessfully. Lower PAI-1 levels were observed in children who survived. Higher baseline sE-selectin levels and lower sICAM-1 and VEGF were observed in children treated unsuccessfully. A decrease in sE-selectin and lower PAI-1 at the 78th day of therapy were associated with better ECO. High baseline VEGF and sE-selectin levels, significant increase in PAI-1, and low initial sICAM-1 levels are prognostics for poorer prognosis in the ALL children.

Interactions between the Cyclooxygenase Metabolic Pathway and the Renin-Angiotensin-Aldosterone Systems: Their Effect on Cardiovascular Risk, from Theory to the Clinical Practice.

Coronary artery disease (CAD) and stroke are the most common and serious long-term complications of hypertension. Acetylsalicylic acid (ASA) significantly reduces their incidence and cardiovascular mortality. The RAAS activation plays an important role in pathogenesis of CVD, resulting in increased vascular resistance, proliferation of vascular-smooth-muscle-cells, and cardiac hypertrophy. Drugs acting on the renin-angiotensin-aldosterone system (RAAS) are demonstrated to reduce cardiovascular events in population with cardiovascular disease (CVD). The cyclooxygenase inhibitors limit the beneficial effect of RAAS-inhibitors, which in turn may be important in subjects with hypertension, CAD, and congestive heart failure. These observations apply to most of nonsteroidal anti-inflammatory drugs and ASA at high doses. Nevertheless, there is no strong evidence confirming presence of similar effects of cardioprotective ASA doses. The benefit of combined therapy with low-doses of ASA is-in some cases-significantly higher than that of monotherapy. So far, the significance of ASA in optimizing the pharmacotherapy remains not fully established. A better understanding of its influence on the particular CVD should contribute to more precise identification of patients in whom benefits of ASA outweigh the complication risk. This brief review summarizes the data regarding usefulness and safety of the ASA combination with drugs acting directly on the RAAS.

Corrigendum to "Low-Level Laser Irradiation Exerts Antiaggregative Effect on Human Platelets Independently on the Nitric Oxide Metabolism and Release of Platelet Activation Markers".

[This corrects the article DOI: 10.1155/2017/6201797.].

Effect of electromagnetic field accompanying the magnetic resonance imaging on human heart rate variability - a pilot study.

The effect of electromagnetic field on cardiovascular system in the literature is defined in ambiguous way. The aim of this study was to evaluate the effect of electromagnetic field on the heart rate variability (HRV) during the examination with magnetic resonance. Forty-two patients underwent Holter ECG heart monitoring for 30 minutes twice: immediately before and after the examination with magnetic resonance imaging (MRI). HRV was analysed by assessing a few selected time and spectral parameters. Is has been shown that standard deviation of NN intervals (SDNN) and very low frequency rates increased, whereas the low frequency:high frequency parameter significantly decreased following the MRI examination. These results show that MRI may affect the HRV most likely by changing the sympathetic-parasympathetic balance.

Effect of endovascular coronary low-level laser therapy during angioplasty on the release of endothelin-1 and nitric oxide.

BACKGROUND: Nitric oxide (NO) and endothelin-1 are potentially significant factors contributing to the pathogenesis of post-angioplasty restenosis. It may be postulated that low-level laser therapy (LLLT) can favorably influence the process of restenosis by affecting those factors. OBJECTIVES: The aim of the study was to evaluate the effect of LLLT applied during percutaneous coronary intervention (PCI) on the factors participating in the homeostasis of vascular tone - NO and endothelin-1. MATERIAL AND METHODS: In a randomized, prospective study of 52 subjects undergoing PCI, an additional 808 nm intravascular LLLT was applied at a dose of 9 J/cm2 in the lesion part. The control group was 49 subjects with PCI only. We assessed the concentration of nitrites/nitrates reflecting NO metabolism as well as endothelin-1 in both groups before PCI, and at 6 h, 12 h and 1 month after the procedure. In addition, half a year after PCI, a follow-up angiography was performed. RESULTS: Statistically higher nitrite/nitrate concentrations were observed in the laser group as compared to the control group in all tests except the pre-PCI assays. Endothelin-1 levels were significantly higher in the laser group 6 h after PCI with a significant decrease in subsequent tests, which was not observed in the control group. The restenosis rate was 15.0% in the laser group and 32.4% in the control group (however the difference was not statistically significant). CONCLUSIONS: LLLT applied during the PCI procedure can influence the process of restenosis by modifying NO and endothelin-1 concentrations.

Effect of Regular Aerobic Activity in Young Healthy Athletes on Profile of Endothelial Function and Platelet Activity.

The aim of the study was to assess the impact of regular professional sports activity on the endothelial and platelet function in young men. The studied group were 79 young men (18-40 y, 25 athletes and 54 without any regular physical activity). The nitric oxide (NO) metabolic pathway intermediates, oxidative stress markers, mediators of inflammation, and platelet aggregation were measured. Flow mediated dilation (FMD) was studied before and after intravenous 16,0 g L-arginine infusion, which was repeated after oral administration of acetylsalicylic acid (ASA-75 mg/day) for 4 days. Both groups had similar demographic characteristics. In the athletes, there was significantly higher hsCRP level, better serum lipid profile, and lower pulse pressure. Greater baseline FMD in athletes and in response to L-arginine disappeared following ASA treatment. There were no differences in the levels of the NO pathway metabolites. The control group was characterized by higher PAI-1 following ASA treatment and sICAM-1 both at baseline and after ASA, but no differences in MDA and 6-keto-PGF-1 alpha and platelet aggregation were noted. Regular professional physical activity modulates endothelial but not platelet function and may thus exert an effect on overall cardiovascular risk.

Low-Level Laser Irradiation Exerts Antiaggregative Effect on Human Platelets Independently on the Nitric Oxide Metabolism and Release of Platelet Activation Markers.

AIM: The goal of the study is to develop a model allowing to investigate precisely the effect of low-level laser therapy (LLLT) on platelet aggregation and to verify the hypothesis regarding the role of the nitric oxide (NO) bioavailability and platelet activation markers in modulating platelet aggregation. METHODS: A total of 41 healthy volunteers at the age of 21-45 years were investigated. At first, platelet aggregation in response to three agonists (TRAP, ADP, and collagen) was evaluated following previous exposure to different doses of laser radiation (λ = 662 nm) to assess the dose-response effect. Subsequently, plasma levels of platelet activation markers (PF4-platelet factor-4 and sP-selectin) as well as the substrate for nitric oxide synthase, L-arginine, and its competitive inhibitors (ADMA-asymmetric dimethylarginine and SDMA-symmetric dimethylarginine) were measured. RESULTS: All doses of laser irradiation significantly reduced the aggregation. However, the most pronounced effect was observed for 19.7 J/cm2. No significant differences in the levels of platelet activation markers nor in the nitric-oxide-metabolic-pathway compounds between analyzed groups were noted. CONCLUSIONS: We have demonstrated in the established in vitro experimental model that the LLLT in a reproducible manner decreases the whole blood platelet aggregation regardless of the NO bioavailability or changes in the platelet activation markers.

Effect of the transdermal low-level laser therapy on endothelial function.

The effect of low-level laser therapy (LLLT) on the cardiovascular system is not fully established. Since the endothelium is an important endocrine element, establishing the mechanisms of LLLT action is an important issue.The aim of the study was to evaluate the effect of transdermal LLLT on endothelial function.In this study, healthy volunteers (n = 40, age = 20-40 years) were enrolled. N = 30 (14 female, 16 male, mean age 30 ± 5 years) constituted the laser-irradiated group (LG). The remaining 10 subjects (6 women, 4 men, mean age 28 ± 5 years) constituted the control group (CG). Participants were subjected to LLLT once a day for three consecutive days. Blood for biochemical assessments was drawn before the first irradiation and 24 h after the last session. In the LG, transdermal illumination of radial artery was conducted (a semiconductor laser λ = 808 nm, irradiation 50 mW, energy density 1.6 W/cm(2) and a dose 20 J/day, a total dose of 60 J). Biochemical parameters (reflecting angiogenesis: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), angiostatin; antioxidative status: glutathione (GSH) and the nitric oxide metabolic pathway: symmetric dimethylarginine (SDMA), asymmetric dimethylarginine (ADMA) and L-arginine) were assessed. In the LG, a significant increase in GSH levels and considerable decrease in angiostatin concentration following the LLLT were observed. No significant differences in levels of the VEGF, FGF, SDMA, ADMA were observed.LLLT modifies vascular endothelial function by increasing its antioxidant and angiogenic potential. We found no significant differences in levels of the nitric oxide pathway metabolites within 24 h following the LLLT irradiation.

Resistant Hypertension.

Resistant hypertension is a severe medical condition which is estimated to appear in 9-18% of hypertensive patients. Due to higher cardiovascular risk, this disorder requires special diagnosis and treatment. The heterogeneous etiology, risk factors and comorbidities of resistant hypertension stand in need of sophisticated evaluation to confirm the diagnosis and select the best therapeutic options, which should consider lifestyle modifications as well as pharmacological and interventional treatment. After having excluded pseudohypertension, inappropriate blood pressure measurement and control as well as the white coat effect, suspicion of resistant hypertension requires an analysis of drugs which the hypertensive patient is treated with. According to one definition - ineffective treatment with 3 or more antihypertensive drugs including diuretics makes it possible to diagnose resistant hypertension. A multidrug therapy including angiotensin - converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, long-acting calcium channel blockers and mineralocorticoid receptor antagonists has been demonstrated to be effective in resistant hypertension treatment. Nevertheless, optional, innovative therapies, e.g. a renal denervation or baroreflex activation, may create a novel pathway of blood pressure lowering procedures. The right diagnosis of this disease needs to eliminate the secondary causes of resistant hypertension e.g. obstructive sleep apnea, atherosclerosis and renal or hormonal disorders. This paper briefly summarizes the identification of the causes of resistant hypertension and therapeutic strategies, which may contribute to the proper diagnosis and an improvement of the long term management of resistant hypertension.

Left ventricular diastolic dysfunction and plasma asymmetric dimethylarginine concentration in persons with essential hypertension.

INTRODUCTION: The study aimed to evaluate the relationship between plasma asymmetric dimethylarginine (ADMA) concentration and development of left ventricular diastolic dysfunction (LVDD) in patients with essential hypertension (EH). Moreover, an attempt was made to define independent risk factors of LVDD in patients with EH. MATERIAL AND METHODS: A group of 106 individuals with EH was obtained (mean age: 47.18 ±11.76 years). Two groups of patients were distinguished: group I - individuals with EH with LVDD (n = 57); group II - persons with EH without LVDD (n = 49). Echocardiographic examination was conducted by the transthoracic technique. High-performance liquid chromatography was used to measure dimethylarginine concentrations. RESULTS: In the group suffering from EH with LVDD, mean ADMA concentration was significantly higher and the ratio of arginine to ADMA was significantly lower than in patients with EH without LVDD. No significant differences were detected between mean concentrations of plasma symmetric dimethylarginine concentration (SDMA) and arginine or in arginine/SDMA ratios in the studied groups. Independent factors of LVDD risk in the study group included higher plasma ADMA concentration, higher serum low-density lipoprotein (LDL) concentration, higher values of body mass index (BMI), higher values of left ventricular mass index (LVMI) and higher values of mean blood pressure (mBP) (ORADMA = 1.731; ORLDL = 1.188; ORBMI = 1.056; ORLVMI = 1.062; ORmBP = 1.014; p < 0.05). CONCLUSIONS: The results of this study showed that ADMA concentration may be of prognostic value in relation to manifestation of LVDD in patients with EH.

Kidney microcirculation response to adenosine stimulation in renal artery stenosis.

The purpose of this study was to assess the vasoconstrictive effects of adenosine in the kidney microcirculation in hypertensive patients with renal artery stenosis (RAS). Twelve patients with resistant hypertension and moderate RAS were selected for the study. In all patients, systolic, diastolic and mean translesional pressure gradients, distal pressure (Pd), aortic pressure (Pa) and Pd/Pa ratio were measured using a pressure guidewire at baseline and after intrarenal bolus administration of 400 µg adenosine. We observed significant changes in mean translesional pressure gradient and systolic Pd after pharmacological stimulation. The results suggest that in hypertensive patients with RAS, vasomotor activity of the kidney microcirculation may be preserved.

Endothelial dysfunction in young healthy men is associated with aspirin resistance.

The aim of this study was to investigate the relation between endothelial dysfunction and aspirin response in a young healthy population (102 men aged 18-40). Initial concentrations of the NO pathway metabolites (ADMA, l-arginine, SDMA), cardiovascular risk markers, oxidative stress markers (MDA, thiol index), sICAM1, sVCAM1, PAI-1, sE-selectin, sP-selectin, VEGF, thromboxane B2, 6-keto-PGF1α and arachidonate-induced platelet aggregation (to separate aspirin resistant from sensitive group) were measured. Flow-mediated-vasodilation (FMD) was measured before and after intravenous infusion of 16.0 g of l-arginine. Measurements were repeated following aspirin administration (75 mg/24 h) for 4 days. Both groups were homogenous regarding demographic and biochemical characteristics reflecting cardiovascular risk. Aspirin resistant subjects were characterized by lower baseline FMD and higher FMD following aspirin and l-arginine treatment, as compared to aspirin sensitive control. MDA and nitrotyrosine were greater, whereas thiol index was lower in aspirin resistant men. The sICAM1, sVCAM1, PAI-1, sE-selectin, sP-selectin and VEGF levels were similar in the analyzed groups. Thromboxane in aspirin resistant subjects was greater both at baseline and following aspirin therapy. However, a significant decrease following aspirin treatment was present in both groups. Aspirin resistance in young men is associated with endothelial dysfunction, which could be due to oxidative stress resulting from lipid peroxidation.

Comparison of the renal hyperemic effects of papaverine and dopamine in patients with renal artery stenosis.

The purpose of this study was to assess the hyperemic effects of papaverine and dopamine in the renal microcirculation of hypertensive patients with renal artery stenosis (RAS). Although a poor correlation between angiographic lesion assessment and its hemodynamic significance is known, angiography is a major criterion for the decision of renal artery stenting. Assessment of the hyperemic translesional pressure gradient was recently shown to be conducive in identifying patients who may benefit from renal revascularization. The study included 14 patients (mean age, 66 ± 11.2 years) with resistant hypertension and moderate RAS. Using a pressure-sensing catheter, systolic, diastolic, and mean translesional pressure gradients, and the distal pressure (Pd):aortic pressure (Pa) ratio (Pd/Pa) were analyzed at baseline and after administration of 40 mg papaverine and 50 µg/kg dopamine. We did not observe significant changes in DG. Dopamine administration resulted in significant changes in systolic and mean translesional pressure gradients and Pd/Pa when compared with baseline (P < .05 for all). Changes in these parameters were caused by a decrease in systolic Pd in comparison with baseline conditions (119 ± 34 mm Hg vs. 101 mm Hg; P < .05). Systolic Pd pressure after papaverine (104 mm Hg) did not change significantly. Systolic and diastolic Pa values did not differ from baseline after either dopamine or papaverine bolus administration.This study indicates that, compared with papaverine, the intrarenal bolus of dopamine in hypertensive patients with RAS remains a more powerful hyperemic agent.

The Use of Low-Level Energy Laser Radiation in Basic and Clinical Research.

Laser radiation has specific attributes: monochromaticity, high coherence and polarization. These properties result in the extensive use of lasers in medicine. Laser devices can be assigned into three basic groups by means of their level of energy: high, medium and low energy. All of these types of radiation are used in medicine. However, the most commonly used, in basic science and clinical studies, is low-energy radiation. Molecular effects of low energy laser irradiation on cells are generally described as "fotobiostimulation" and "fotobiomodulation". These phenomena consequently lead to attempts to exploit this kind of radiation as a treatment method (low-level laser therapy-LLLT). Areas in which LLLT is used are: regenerative medicine (for healing wounds and ulcers); aesthetic medicine (to improve appearance of scars); dentistry (to accelerate healing of implants); physiotherapy (to reduce chronic pain syndromes), orthopedics (in bone healing) and cardiology (as a prevention of restenosis after percutaneous coronary intervention). This paper discusses the medical applications of LLLT which are used in daily clinical practice as well as those used in basic science.

Effects of intravascular low-level laser therapy during coronary intervention on selected growth factors levels.

OBJECTIVE: The objective of this study was to evaluate the effect of intravascular low-level laser therapy (LLLT) on selected growth factor levels in subjects undergoing percutaneous coronary interventions (PCI). BACKGROUND DATA: Restenosis remains the main problem with the long-term efficacy of PCI, and growth factors are postulated to play a crucial role in the restenosis cascade. MATERIALS AND METHODS: In a randomized prospective study, an 808 nm LLLT (100 mW/cm2, continuous wave laser, 9 J/cm2, illuminated area 1.6-2.5 cm2) was delivered intracoronarily to patients during PCI. Fifty-two patients underwent irradiation with laser light, and 49 constituted the control group. In all individuals, serum levels of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), and fibroblast growth factor-2 (FGF-2) were measured before angioplasty, then 6 and 12 h and 1 month after the procedure. In all patients, a control angiography was performed 6 months later. RESULTS: There were no significant differences in IGF-1 and VEGF levels between the groups. While evaluating FGF-2, we observed its significantly lower levels in the irradiated patients during each examination. There was a significant increase in TGF-ß1 level in control group after 12 h of observation. In the irradiated individuals, control angiography revealed smaller late lumen loss and smaller late lumen loss index as compared with the control group. The restenosis rate was 15.0% in the treated group, and 32.4% in the control group, respectively. CONCLUSIONS: LLLT decreases levels of TGF-ß1 and FGF-2 in patients undergoing coronary intervention, which may explain smaller neointima formation.

Renal artery stenosis in patients with resistant hypertension.

The aim of the study was to assess the significance of renal translesional pressure gradients in predicting improvement in resistant hypertension after stenting for moderate renal artery stenosis (RAS). In 37 patients with RAS and resistant hypertension subjected to renal stenting, translesional pressure gradients both at rest and hyperemic were measured using a pressure guidewire. Twenty-four-hour ambulatory blood pressure measurements were performed in all patients on admission and 3 months after the intervention. Angioplasty was successful in all patients, with reduction of artery diameter stenosis from 60 ± 12% to 10 ± 6% (p <0.0001). At 3 months, with maintained hypotensive agents (4.0 ± 1.4 vs 4.0 ± 1.6), significant reductions in systolic blood pressure (SBP) and diastolic blood pressure were noted (-5 and -2 mm Hg, respectively). In multivariate analysis, the mean baseline gradient (MBG) was the only independent predictor of improvement in SBP (regression coefficient 0.292; standard error 0.11; p value 0.014). In the receiver operating characteristic curve analysis, MBG had a larger area under the curve than other parameters, and the MBG >22 mm Hg had the highest sensitivity, specificity, and accuracy (50%, 95%, and 0.74%, respectively) in predicting hypertension improvement after stenting. In patients with MBG >22 mm Hg, SBP decreased by 12 versus 3 mm Hg (p <0.01) in patients with MBG ≤22 mm Hg, whereas diastolic blood pressure in both groups decreased by 3 versus 1 mm Hg, respectively (NS). In conclusion, MBG value of >22 mm Hg provides the highest accuracy in predicting hypertension improvement after stenting for moderate RAS in patients with resistant hypertension.

Influence of low-power laser illumination on pro-inflammatory response in human endothelial cells stimulated with interleukin-1a.

BACKGROUND: Regarding recent findings on the proven influence of laser light on healing and endothelial regeneration processes, this study was conducted in order to examine the influence of low-power laser illumination on the endothelial inflammatory response. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) isolated from umbilical cord, cultured in standard conditions, were harvested and passaged in 24-well plates. Laser influence on HUVEC inflammatory response was measured by stimulating them with Interleukin-1ß (IL-1ß) followed by laser light illumination. A 808-nm wave length laser diode and light energy doses of 1.5 and 4.5 J/cm(2) were used (50 mW for 90 and 270 s respectively). The response was measured by assessing Cluster of differentiation 54 (CD54), Cluster of differentiation 62E (CD62E), Monocyte chemotactic protein-1 (MCP-1) expression and von Willebrand factor (vWF) release, at 6 and 24 h after stimulation. The MCP-1 and vWF activity in cell supernatants was measured with an enzyme-linked immunosorbent assay (ELISA) kit. Cytofluorometry was used to assess CD54 and CD62E expression. RESULTS: MCP-1 concentration in supernatants from HUVECs was significantly lower 6 h after 4.5 J/cm(2) stimulation compared to IL-1ß-stimulated cells. No changes in MCP-1 levels after IL-1ß stimulation plus 1.5 J/cm(2) illumination, compared to IL-1ß stimulated HUVECs were noted. IL-1ß stimulation significantly enhanced the concentration of vWF and the expression of CD54 and CD62E. Both energies of laser light illumination inhibited the IL-1ß-induced increase of CD54 and CD62E concentration. vWF activity after illumination was comparable to that of unstimulated cells. There were no significant differences in the viable cell count between the groups tested. CONCLUSION: Low-power laser illumination diminishes the pro-inflammatory and pro-coagulant activity of IL-1ß-stimulated HUVECs.