Effects of penta-O-galloyl-ß-D-glucose on human neutrophil function: significant down-regulation of L-selectin expression.

Penta-O-galloyl-ß-D-glucose (PGG) occurrs in high concentrations in medicinal herbs such as Rhus chinensis, Paeonia suffruticosa, Acer truncatum and Terminalia chebula, which demonstrate anti-inflammatory activity. We investigated the effect of PGG on stimulated and non-stimulated neutrophils in processes which included reactive oxygen species generation (ROS), metalloproteinase-9 and interleukin-8 secretion (IL-8), ß2 integrin (CD11b) and L-selectin (CD62L) expression and apoptosis. In concentrations of 5 µM-20 µM, PGG demonstrated statistically significant inhibition of ROS generation, IL-8 secretion and ß2 integrin expression in stimulated neutrophils. The inhibition of L-selectin expression by PGG resulted in prevention in neutrophils' endothelial attachment. The result obtained may explain the anti-inflammatory activity of this compound and underline the contribution of PGG in the activity of PGG rich plant extracts.

Extracts from Epilobium sp. herbs, their components and gut microbiota metabolites of Epilobium ellagitannins, urolithins, inhibit hormone-dependent prostate cancer cells-(LNCaP) proliferation and PSA secretion.

Extracts from Epilobium sp. herbs have been traditionally used in the treatment of prostate-associated ailments. Our studies demonstrated that the extracts from Epilobium angustifolium, Epilobium parviflorum and Epilobium hirsutum herbs are potent prostate cancer cells (LNCaP) proliferation inhibitors with IC50 values around 35 µg/ml. The tested extracts reduced prostate specific antigen (PSA) secretion (from 325.6 ± 25.3 ng/ml to ~90 ng/ml) and inhibited arginase activity (from 65.2 ± 1.1 mUnits of urea/mg of protein to ~40 mUnits of urea/mg protein). Selected constituents of extracts (oenothein B, quercetin-3-O-glucuronide, myricetin-3-O-rhamnoside) were proven to be active in relation to LNCaP cells. However, oenothein B was the strongest inhibitor of cells proliferation (IC50 = 7.8 ± 0.8 µM), PSA secretion (IC50 = 21.9 ± 3.2 µM) and arginase activity (IC50 = 19.2 ± 2.0 µM). Additionally, ellagitannins from E. hirustum extract were proven to be transformed by human gut microbiota into urolithins. Urolithin C showed the strongest activity in the inhibition of cell proliferation (IC50 = 35.2 ± 3.7 µM), PSA secretion (reduced PSA secretion to the level of 100.7 ± 31.0 ng/ml) and arginase activity (reduced to the level of 27.9 ± 3.3 mUnits of urea/mg of protein). Results of the work offer an explanation of the activity of Epilobium extracts and support the use of Epilobium preparations in the treatment of prostate diseases.

Ex vivo effects of an Oenothera paradoxa extract on the reactive oxygen species generation and neutral endopeptidase activity in neutrophils from patients after acute myocardial infarction.

Oxidative stress induced by reactive oxygen species (ROS) is considered to play an important part in the aetiology of coronary heart disease. Apart from ROS, neutrophils are a source of neutral endopeptidase (NEP) that inactivates protective natriuretic peptides. The aim of the present study was to evaluate the in vitro ROS generation and inhibition of NEP activity in neutrophils obtained from healthy volunteers and from patients after acute myocardial infarction (AMI) by an aqueous extract of Oenothera paradoxa. Neutrophils isolated from AMI patients showed two-fold higher ROS generation compared with cells from healthy donors, especially in the lucigenin-enhanced luminescence model, which suggests intensive O2⁻ generation. The addition of O. paradoxa extract at concentrations of 0.2, 2 and 20 µg/mL resulted in a significant reduction in ROS generation. The extracellular NEP activity was higher in patients after AMI compared with healthy individuals (15.0 ± 0.9 versus 10.3 ± 0.5 nmol AMC/10(6) cells/60 min; p = 0.001). The addition of O. paradoxa extract at concentrations of 20, 50 and 100 µg/mL resulted in a significant reduction in NEP activity in both groups. O. paradoxa extract appears to be an interesting candidate for supplementation in the prevention of cardiovascular diseases.

Is there an effect of folic acid supplementation on the coagulation factors and C-reactive protein concentrations in subjects with atherosclerosis risk factors?

INTRODUCTION: Folic acid (FA) may delay the formation of atherosclerotic lesions. Increased plasma levels of von Willebrand factor (VWF) are observed in cardiovascular disease, which leads to higher risk of thrombosis. Fibrinogen (Fb) is a well-documented risk factor of cardiovascular disease. The aim of this study was to analyze the effect of FA supplementation on the Fb, VWF and C-reactive protein (CRP) plasma concentrations in subjects with atherosclerosis risk factors. MATERIAL/METHODS: The study enrolled 124 Caucasian individuals (60 M, 64 F) with atherosclerosis risk factors--family history of premature ischaemic stroke, arterial hypertension, dyslipidaemia, overweight and obesity, cigarette smoking and low physical activity. The participants were asked to take FA in the low dose of 0.4 mg/24 h for three months. RESULTS: After FA supplementation a significant reduction of the VWF concentrations in females (76.6 vs 72.3%; p=0.028) and in males (75.5 vs 66.9%; p=0.001) was observed. Among women and men with dyslipidaemia concentrations of VWF decreased after FA supplementation (76.8% vs 69.6%; p=0.003 and 76.7% vs 67.8%; p=0.001 respectively). Among females and males with BMI ≥25 kg/m² concentrations of VWF decreased only in men (77.6% vs 66.5%; p=0.001). In female and male smokers supplementation of FA decreased VWF concentrations (82.5% vs 74.4%; p=0.012 and 76.6% vs 69.5%; p=0.036 respectively). DISCUSSION: The results of our study suggest that there is an effect of FA supplementation on VWF concentrations in subjects with atherosclerosis risk factors.

Silymarin inhibits endothelial progenitor cells' senescence and protects against the antiproliferative activity of rapamycin: preliminary study.

Rapamycin, an antiproliferative agent used on drug-eluting stents, induces endothelial progenitor cells (EPCs) senescence through telomerase inactivation and may impair the reendothelization of an injured arterial wall, leading to thrombosis. We examined whether silymarin, a complex of flavonolignans with hepatoprotective and antioxidative properties, can protect EPCs against rapamycin-induced senescence. Mononuclear cells were isolated from peripheral blood of healthy volunteers. EPCs were cultured in endothelial cell growth medium-2 in the presence or absence of rapamycin (0.1 ng/mL) and/or silymarin (12.5­50 µg/mL). EPCs senescence­associated b-galactosidase activity, telomerase activity, and prolifertive activity were measured. The influence on tubular-like structure formation in vitro was investigated, and colony-forming assay on methylcellulose plates was performed. Silymarin increased telomerase activity 3-fold, reduced the number of senescent cells, and increased EPC proliferative activity (up to 64%) in comparison with cells cultured with rapamycin alone. Moreover, silymarin partially prevented impairment of tubular-like structure formation in Matrigel by rapamycin. These findings suggest that silymarin counteracts the inhibitory effects of rapamycin in EPCs. Silymarin may protect EPCs against the antiproliferative effects of rapamycin and restore their reconstructive ability.

Reduced kidney function estimated by cystatin C and clinical outcomes in hypertensive patients with coronary artery disease: association with homocysteine and other cardiovascular risk factors.

AIMS: To evaluate the association between serum cystatin C and homocysteine concentrations, cardiovascular risk factors and cardiovascular events in hypertensive patients with coronary artery disease (CAD). METHODS: 260 patients with hypertension and CAD (mean age 56.9 +/- 9.3) were included. During a mean 40-month follow-up the combined end-point of death from all causes, non-fatal myocardial infarction and stroke or coronary revascularization was assessed. RESULTS: Subjects in the highest serum cystatin C quartile (>103.4 nmol/l) as compared with the lowest were older, were characterized by a higher frequency of multivessel CAD, higher levels of homocysteine (13.2 +/- 5.2 vs. 11.4 +/- 4.2 micromol/l; p < 0.01), fibrinogen and high-sensitivity C-reactive protein and by an increased intima-media thickness. Combined end-point occurred twice as frequently in the 4th quartile of serum cystatin C as compared with the 1st quartile (10.8 vs. 20.3%; p = 0.11). In an univariate analysis, but not in a multivariate model, cystatin C concentration predicted the combined end-point (Exp(B) = 1.096; p < 0.05). CONCLUSION: In hypertensive patients with CAD, serum cystatin C level was independently associated with the extent of CAD, homocysteine plasma level and traditional vascular risk factors. However, serum cystatin C concentration did not independently predict the combined end-point.

Oleacein and Foam Cell Formation in Human Monocyte-Derived Macrophages: A Potential Strategy Against Early and Advanced Atherosclerotic Lesions.

BACKGROUND: Oleacein is a secoiridoid group polyphenol found mostly in Olea europea L. and Ligustrum vulgare L. (Oleaceae). The aim of the present study was to investigate a potential role of oleacein in prevention of the foam cell formation. MATERIALS AND METHODS: Oleacein was isolated from Ligustrum vulgare leaves. Human monocyte-derived macrophages were obtained from monocytes cultured with Granulocyte-macrophage colony-stimulating factor (GM-CSF)Then, cells were incubated with 20 M or 50 M of oleacein and with oxidized low-density lipoprotein (oxLDL) (50 g/mL). Visualization of lipid deposition within macrophages was carried out using Oil-Red-O. Expression of CD36, Scavenger receptor A1 (SRA1) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) was determined by Reverse transcription polymerase chain reaction (RT-PCR) and by flow cytometry. Apoptosis was determined by flow cytometry using Annexin V assay. STAT3 and Acyl-coenzyme A:cholesterol acyltransferase type 1 (ACAT1)levels were determined by ELISA. P-STAT3, P-JAK1, P-JAK2 expressions were determined by Western blot (WB). RESULTS: Oleacein in dose-dependent manner significantly reduced lipid deposits in macrophages as well as their expression of selected scavenger receptors. The highest decrease of expression was found for CD36 and SRA1 receptors, from above 20% to more than 75% compared to oxLDL and the lowest for LOX-1 receptor, from approx. 8% to approx. 25% compared to oxLDL-stimulated macrophages. Oleacein significantly reduced (2.5-fold) early apoptosis of oxLDL-stimulated macrophages. Moreover, oleacein significantly increased the protein expression of JAK/STAT3 pathway and had no effect on ACAT1 level. CONCLUSIONS: Our study demonstrates, for the first time, that oleacein inhibits foam cell formation in human monocyte-derived macrophages and thus can be a valuable tool in the prevention of early and advanced atherosclerotic lesions.

Hp1-1 as a Genetic Marker Regulating Inflammation and the Possibility of Developing Diabetic Complications in Patients with Type 2 Diabetes-Cohort Studies.

BACKGROUND: This study assessed the influence of the haptoglobin phenotype on markers regulating inflammation in patients with type 2 diabetes. METHODS: The haptoglobin phenotypes, soluble form of CD163 receptor (sCD163), p53 concentrations and high mobility group box protein 1 (HMGB1), interleukin 10 (IL-10) secretion in serum were assayed via ELISA tests. In the first part of the project, patients were divided into three groups which differed by the haptoglobin phenotype, and afterwards into two groups according to the criterion of the presence or absence of cardiovascular disease. RESULTS: Diabetic patients with haptoglobin phenotype 1-1 (Hp1-1) had a significantly higher concentration of IL-10 and sCD163 compared to haptoglobin phenotype 2-1 (Hp2-1) and haptoglobin phenotype 2-2 (Hp2-2). Moreover, diabetic patients with Hp1-1 had a significantly lower concentration of p53 and HMGB1 compared to diabetic patients with Hp2-1 and Hp2-2. The results have shown that diabetics with Hp2-1 had a significantly lower postprandial glucose level compared to diabetics with Hp2-2. Apart from that, there were no differences in the occurrence of haptoglobin variants between patients with or without cardiovascular disease. CONCLUSIONS: Our study provides new data for a relationship between the type of haptoglobin in patients with type 2 diabetes and the concentration of factors that regulate the body's inflammation. We have shown that the Hp1-1 can serve as a genetic marker of inflammatory processes.

1,2,3,4,6-Penta-O-galloyl-ß-d-glucose modulates perivascular inflammation and prevents vascular dysfunction in angiotensin II-induced hypertension.

BACKGROUND AND PURPOSE: Hypertension is a multifactorial disease, manifested by vascular dysfunction, increased superoxide production, and perivascular inflammation. In this study, we have hypothesized that 1,2,3,4,6-penta-O-galloyl-ß-d-glucose (PGG) would inhibit vascular inflammation and protect from vascular dysfunction in an experimental model of hypertension. EXPERIMENTAL APPROACH: PGG was administered to mice every 2 days at a dose of 10 mg·kg-1 i.p during 14 days of Ang II infusion. It was used at a final concentration of 20 µM for in vitro studies in cultured cells. KEY RESULTS: Ang II administration increased leukocyte and T-cell content in perivascular adipose tissue (pVAT), and administration of PGG significantly decreased total leukocyte and T-cell infiltration in pVAT. This effect was observed in relation to all T-cell subsets. PGG also decreased the content of T-cells bearing CD25, CCR5, and CD44 receptors and the expression of both monocyte chemoattractant protein 1 (CCL2) in aorta and RANTES (CCL5) in pVAT. PGG administration decreased the content of TNF+ and IFN-γ+ CD8 T-cells and IL-17A+ CD4+ and CD3+ CD4- CD8- cells. Importantly, these effects of PGG were associated with improved vascular function and decreased ROS production in the aortas of Ang II-infused animals independently of the BP increase. Mechanistically, PGG (20 µM) directly inhibited CD25 and CCR5 expression in cultured T-cells. It also decreased the content of IFN-γ+ CD8+ and CD3+ CD4- CD8- cells and IL-17A+ CD3+ CD4- CD8- cells. CONCLUSION AND IMPLICATION: PGG may constitute an interesting immunomodulating strategy in the regulation of vascular dysfunction and hypertension. LINKED ARTICLES: This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc.

Inhibitory effect of Ligustrum vulgare leaf extract on the development of neuropathic pain in a streptozotocin-induced rat model of diabetes.

BACKGROUND: Chronic hyperalgesia and allodynia associated with progressive damage of peripheral neurons are the most prevalent complications of diabetes mellitus. Plants belonging to the family of Oleaceae were traditionally used in folk medicine for the management of diabetes. HYPOTHESIS/PURPOSE: The aim of this study was to investigate whether an aqueous extract from the leaves of Ligustrum vulgare (common privet) could be useful to target neuropathic pain in a rat streptozotocin (STZ) model of diabetes. METHODS: The chemical composition of the aqueous extract from privet leaf was characterized with the UHPLC-DAD-MS method and the analytical quantification of its constituents was performed with HPLC-DAD. Mechanical hyperalgesia and allodynia were evaluated with the Randall-Selitto and von Frey tests. RESULTS: Our investigation revealed the presence of secoiridoids: oleacein (23.48 ±â€¯0.87 mg/g), oleocanthal (8.44 ±â€¯0.08 mg/g), oleuropein (1.50 ±â€¯0.01 mg/g), as well as phenylpropanoids: echinacoside (6.46 ±â€¯0.07 mg/g), verbascoside (4.03 ± 0.04 mg/g) and p-coumaroyl glucarates in the dried aqueous extract of privet leaves. Behavioral data indicated that chronic intraperitoneal administration of the extract (50-200 mg/kg) for 21 days resulted in a decrease in diabetes-induced hyperalgesia and allodynia. Blood glucose levels remained unaltered, while body weight and water intake decreased significantly. CONCLUSION: The aqueous privet leaf extract could serve useful in facilitating treatment of painful diabetic neuropathy. Additionally, the study showed that the antihyperalgesic activity of Ligustrum vulgare leaf extract is not likely related to its antihyperglycemic properties.

Cardiovascular risk factors in hypertensive patients with coronary artery disease and coexisting renal artery stenosis.

OBJECTIVE: The aim of our study was to examine the association between the presence of atherosclerotic renal artery stenosis (RAS) and coexisting cardiovascular risk factors in hypertensive patients with coronary artery disease (CAD). METHODS: A total of 333 consecutive hypertensive patients (239 men, 94 women) with CAD underwent clinically indicated non-emergency coronary angiography, followed by renal angiography. Before catheterization clinical examination was performed to determine demographics, cardiac history, known duration of hypertension, cardiovascular risk factors, features of extracoronary vascular disease and related comorbidities. Blood samples for all biochemical evaluations--including highly sensitive C-reactive protein (hsCRP), fibrinogen and homocysteine--were taken. Ambulatory blood pressure monitoring (ABPM), echocardiography and carotid and femoral ultrasound followed by a duplex colour Doppler examination were performed. RESULTS: Significant RAS (> 50% lumen narrowing) was identified in 40 patients (12%) and non-significant RAS (< 50%) was found in 45 (13.5%) subjects. Patients with significant RAS were older (59.8 versus 56.6 years, P < 0.05) and were characterized by higher systolic ambulatory blood pressure level. Patients with RAS had significantly higher levels of creatinine, hsCRP, fibrinogen and homocysteine and lower creatinine clearance than patients without RAS. Multivessel coronary artery disease (MVD) was more frequent in patients with significant RAS. Patients with significant RAS had significantly higher left ventricular mass index (LVMI) and lower ejection fraction (EF) as compared with those without RAS. Patients with RAS were more often characterized by the presence of carotid and femoral artery atherosclerosis and significantly more pronounced increase in carotid intima-media thickness (IMT) as compared with non-RAS subjects. In a multivariate stepwise logistic regression model carotid IMT [odds ratio (OR) 1.15; 95% confidence interval (CI) 1.03-1.29, P < 0.05], number of coronary arteries stenosed (OR 1.61; 95% CI 1.01-2.56, P < 0.05), creatinine concentration (for 10 micromol/l increase, OR 1.15; 95% CI 1.04-1.28, P < 0.01), body mass index (BMI) (OR 0.86; 95% CI 0.75-0.97, P < 0.05) and number of antihypertensive drugs (OR 1.76; 95% CI 1.18-2.62, P < 0.05) were independently associated with RAS. The areas under receiver operating characteristic curves for carotid IMT, number of coronary arteries stenosed, creatinine concentration, BMI and number of antihypertensive drugs were 0.749, 0.633, 0.703, 0.350 and 0.677, respectively (P < 0.01 for all values). CONCLUSIONS: In conclusion, renal artery stenosis is prevalent in a significant proportion of patients undergoing cardiac catheterization. Renal angiography should be considered particularly in hypertensive patients with multivessel coronary disease coexisting with cardiovascular risk factors, even moderately impaired renal function and increased carotid IMT or vascular disease elsewhere.

Carotid intima-media thickness as a marker of cardiovascular risk in hypertensive patients with coronary artery disease.

BACKGROUND: The aim of this study was to examine the significance of ultrasound-measured carotid intima-media thickness (CIMT) in high-risk patients with hypertension and coronary artery disease (CAD), as an independent prognostic factor in determining the risk of all-cause death or future cardiovascular events. METHODS: The study included 297 consecutive patients (mean age +/- SD, 57 +/- 9.4 years) with diagnosed hypertension and CAD, referred for coronary angiography. The mean of maximal CIMT in two arterial segments bilaterally was calculated. The primary endpoint was a patient's death from all causes. Death, stroke, or myocardial infarction comprised the secondary, composite endpoint. RESULTS: There was a follow-up of 1 to 79 (mean, 41) months. The predictors of death in a multivariate Cox proportional hazards model were the number of stenosed coronary arteries (P = .007) and CIMT (P = .001). The risk of the secondary, composite endpoint (death, stroke, or myocardial infarction) was determined by diabetes (P = .008) and CIMT (P = .010). Nearly 99% of patients with "low CIMT" (< or =1.13 mm) survived for 5 years, versus 78% with "high CIMT" >1.13 mm (log-rank test; P < .001). For the secondary, composite endpoint (death, stroke, or myocardial infarction), the event-free survival rate was 95% (low CIMT), versus 74% after 5 years (high CIMT) (P < .008). CONCLUSIONS: Intima-media thickness of the carotid arteries is a strong and independent predictor of death and serious cardiovascular events in hypertensive patients with CAD referred for coronary angiography.

Magnesium enhances opioid-induced analgesia - What we have learnt in the past decades?

Opioids are increasingly used in alleviating pain, including cancer-related pain and postoperative pain. Unfortunately, the development of tolerance, the resistance of neuropathic pain on opioid analgesia or other undesirable effects may limit their utility. In order to reduce opioid doses, and thereby to avoid the risk of side effects and sudden deaths due to overdosing, attempts have been made to introduce co-analgesics. Due to an increasing amount of data concerning a potential enhance of opioid analgesia by the physiological antagonist of N-methyl-d-aspartate receptors, magnesium ions (Mg2+), a concomitant use of such a combination seems to be interesting from a clinical point of view. Therefore, the aim of this review is to provide an analysis of existing preclinical and clinical studies in the context of the benefits of using this combination in clinical practice. A potential mechanism of magnesium - opioid interaction is also suggested. The potential influence of Mg on opioid adverse/side effects as well as conclusions on the safety of combined administration of magnesium and opioid drugs were also summarized. Data from animal studies indicate that magnesium increases opioid analgesia in chronic (e.g., neuropathic, inflammatory) as well as acute pain. In clinical trials, most authors confirmed that magnesium reduces opioid consumption and alleviates postoperative pain scores while not increasing the risk of side effects after opioids. However, more clinical studies are needed concerning an influence of Mg on opioid activity in other difficult to treat types of pain, especially neuropathic and inflammatory.

Oleacein may inhibit destabilization of carotid plaques from hypertensive patients. Impact on high mobility group protein-1.

BACKGROUND: In patients with hypertension the haemorrhage into carotid atherosclerotic plaque increases risk of plaque destabilization and rupture. Our previous study showed that oleacein, a secoiridoid present in extra virgin olive oil, enhanced uptake of haemoglobin-haptoglobin complex and change macrophage phenotype from pro-inflammatory M1 to anti-inflammatory M2. PURPOSE: The aim this study was to investigate a potential role of oleacein in attenuation of carotid plaque destabilisation ex vivo. METHODS: Samples of atherosclerotic plaque were harvested from 20 patients with hypertension /11 women and 9 men/, who underwent carotid endarterectomy after transient ischemic attacks. Matching pieces of each plaque were incubated with increased concentration of pure oleacein /range 0-20 µM/ for 24 h. HMGB1, MMP-9, MMP-9/NGAL, TF and IL-10, as well as HO-1 secretion from plaque was measured by enzyme-linked immunosorbent assay /ELISA/. Statistical significance was set at P < 0.05 and P < 0.001. RESULTS: Oleacein at the concentrations of 10 and 20 µM significantly (P < 0.001) decreased secretion of HMGB1 (up 90%), MMP-9 (up to 80%), MMP-9/NGAL complex (up to 80%) and TF (more than 90%) from the treated plaque, as compared to control. At the same time IL-10 and HO-1 release increased by more than 80% (P < 0.001). CONCLUSION: Our results indicate that oleacein possess ability to attenuate the destabilization of carotid plaque and could be potentially useful in the reduction of ischemic stroke risk.

Familial lecithin-cholesterol acyltransferase deficiency: biochemical characteristics and molecular analysis of a new LCAT mutation in a Polish family.

Familial LCAT deficiency (FLD) is a rare genetic disorder associated with corneal opacities, anaemia and proteinuria with renal failure. Here we report detailed analyses on plasma lipids, lipoproteins, and the molecular defect in two siblings from a Polish family presenting classical symptoms of FLD and their family members with newly discovered Val309Met mutation in exon 6 of LCAT gene. Both patients displayed low total (2.19 and 2.94 mmol/l) and HDL-cholesterol concentrations (0.52 and 0.48 mmol/l), low percentage of cholesteryl esters (CE) (11.1 and 12%), and decreased apo AI and apo AII serum levels. Low LDL-cholesterol, apo B and Lp(a) levels, and increased oleate/linoleate ratios in CE could be of importance in the development of atherosclerosis in these patients with low HDL-cholesterol. LCAT activity was 10% of normal, alpha-LCAT activity was 0, and LCAT concentration was undetectable by immunoassay. Plasma CETP activity was at lower limits of normal. PCR and sequence analysis of DNA from the proband and affected brother revealed a novel G-->A mutation in exon 6 of LCAT gene, which resulted in an amino acid substitution of valine for methionine (Val309Met). The proband and affected brother were both homozygous carriers, while the mother, siblings and children of patients were heterozygous carriers of a newly discovered mutation. This is the first LCAT mutation described in the Slavic population.

Is there an association between angiotensin-converting enzyme gene polymorphism and functional activation of monocytes and macrophage in young patients with essential hypertension?

BACKGROUND: This study was undertaken to determine whether the phenotype of monocytes and monocyte-derived macrophages is more proatherogenic in young persons with arterial hypertension and whether this phenotype is affected by smoking or polymorphism of the angiotensin-converting enzyme (ACE) gene. METHODS: We enrolled 40 young patients (24.1 +/- 4.7 years) with previously untreated arterial hypertension and 40 age-matched healthy controls. There were 20 smokers and 20 non-smokers in each group. RESULTS: In the hypertensive group, we found enhanced monocyte expression of CD11a (P < 0.001), reduced expression of CD49d (P < 0.001) and CD62L (P < 0.005), greater oxidative stress in resting and phorbol-12-mistrate-13-acetate-stimulated monocytes (P < 0.001), enhanced adhesion of monocytes to endothelial cells (P < 0.001), greater expression of CD36 on monocyte-derived macrophages (P < 0.001), and enhanced production of reactive oxygen species by resting and phorbol-12-mistrate-13-acetate-stimulated macrophages (P < 0.001). Cigarette smoking by hypertensive patients was associated with enhanced (P < 0.002) CD11a expression. There were no associations of ACE gene polymorphism with cellular expression or reactive oxygen species production studied among hypertensive patients. Only CD62L expression in DD homozygote participants was higher (P < 0.039) than in II homozygote participants. CONCLUSIONS: It is concluded that arterial hypertension affects the function of monocytes/macrophages in young persons. Polymorphism of the ACE gene is without effect on the functional activation of monocytes and macrophages.

[The assessment of the influence of natural coffee and its modified form on the level of homocysteine, vitamin B6 and folic acid in healthy volunteers]. / Ocena wplywu kawy naturalnej i jej formy zmodyfikowanej na stezenie homocysteiny oraz witaminy B6 i kwasu foliowego u zdrowych wolontariuszy.

UNLABELLED: The aim of our investigation was the assessment of the influence of natural coffee and that modified by water and pressure extraction (60% less of 2-methyl isoborneol) on the level of homocysteine, folic acid and vitamin B6 in healthy volunteers. MATERIAL AND METHODS: The study was conducted on 36 healthy volunteers. 20 women and 16 men; smokers constituted half of the group. The study was conducted as a double blind trial (coffee without labels) after randomization into two groups. Initially for 4 weeks, one group drank natural coffee and the other a modified one. After four weeks there was a 28-day break in drinking coffee, after which the groups swapped roles and another trial lasted for the subsequent 4 weeks. All people examined drank three servings of coffee a day brewed from 13 g of material in 180 ml of boiling water. Throughout the entire experiment the examined subjects did not change their diets and did not take any vitamin supplements. Blood for analysis was drawn four times and the following analyses were carried out. homocysteine, folic acid, vitamin B6 total, LDL and HDL-cholesterol, triglicerides, Lp(a) and fibrinogen. RESULTS: We found a significant increase level of plasma homocysteine from 9.6 to 11.4 micromol/l (p < 0.001) in persons drinking natural, unfiltered coffee. However drinking modified coffee free from irritants resulted in a tendency towards lowering the level of homocysteine (from 9.1 to 8.7 micromol/l). CONCLUSIONS: From the above study it may be concluded that lowering the content of irritants in coffee results in reducing its undesired influence on the homocysteine level. Reduction of natural coffee consumption or its change on coffee with lowering the content of irritants should be recommended to cardiovascular disease persons.

Cardioprotective effects of Aronia melanocarpa anthocynanins. From laboratory experiments to clinical practice.

The role of polyphenols in the cardiovascular diseases prevention is still a matter of scientific discussion. However, recent clinical studies indicate that intake of anthocyanins and in a lesser extent procyanidins can participate in prevention of hypertension and type 2 diabetes. Fruits of Aronia melanocarpa (chokeberry) are known to be a reach source of these polyphenols. Moreover, its extracts were shown to express strong antioxidant, antiinflammatory, vasorelaxant and antithrombotic properties. The aim of the review is to summarize the results of the hitherto research regarding the biological effects at the molecular and clinical level.

Differences in achieving treatment goals with statin use in various regions of Poland--3ST-POL study results.

INTRODUCTION AND OBJECTIVE: Dyslipidemia is the most common factor leading to ischemic heart disease, which is one of the leading causes of death. The use of statins is the most important preventative measure of ischemic heart disease; however, their efficacy in patients in Poland is still too low. The purpose of this study was to evaluate regional differences in achieving treatment goals in total cholesterol (TC) and LDL cholesterol levels in patients treated with statins on an outpatient basis. MATERIALS AND METHODS: A survey was used to evaluate efficacy of treatment, completed by 49,950 patients in Poland treated with statins in 2008. The territory of Poland was divided into 4 research regions: the Northeast (NE), Northwest (NW), Southeast (SE), and Southwest (SW) regions. RESULTS: The largest group of patients resided in the SW region, the smallest in the SE region. Participants of the study suffered from hypercholesterolemia, on average, for at least a year before completing the study survey. Effective treatment leading to achievement of target TC was observed in less than 10% of the patients. Rate of achievement of target cholesterol levels was highest in the NE region, lowest in the NW region. Cardiologists were more successful in achieving therapeutic goals than GPs. Similar correlations between regions and doctors' specializations were observed for LDL values. CONCLUSIONS: Significant differences in the efficacy of treatment with statins were observed among the study group and were evaluated based on achievement of target TC and LDL cholesterol levels. Better results achieved in the NE region may be because the region includes the Masovian province, which is the most economically developed region in Poland.