text:
The present study was designed to examine the effects of lifestyle modification on key contributing factors to atherogenesis, including oxidative stress, inflammation, chemotaxis, and cell adhesion. Obese men (n = 31), 15 of whom had metabolic syndrome, were placed on a high-fiber, low-fat diet in a 3-wk residential program where food was provided ad libitum and daily aerobic exercise was performed. In each subject, pre- and postintervention fasting blood was drawn for circulating levels of serum lipids, glucose and insulin (for estimation of insulin sensitivity), oxidative stress-generating enzyme myeloperoxidase and marker 8-isoprostaglandin F2α, the inflammatory protein C-reactive protein, soluble ICAM-1 as an indicator of endothelial activation, sP-selectin as a marker of platelet activation, the chemokine macrophage inflammatory protein-1α, and total matrix metalloproteinase-9. Using subject sera and human aortic endothelial cell culture systems, we measured VCAM-1 cell surface abundance and monocyte chemotactic protein-1, nitric oxide, superoxide, and hydrogen peroxide production in vitro by fluorometric detection. Also determined in vitro was serum-induced, monocyte adhesion and monocyte chemotactic activity. After 3 wk, significant reductions (P < 0.05) in body mass index, all serum lipids and lipid ratios, fasting glucose, insulin, homeostasis model assessment for insulin resistance, myeloperoxidase, 8-isoprostaglandin F2α, C-reactive protein, soluble ICAM-1, soluble P-selectin, macrophage inflammatory protein-1α, and matrix metalloproteinase-9 were noted. In vitro, serum-stimulated cellular VCAM-1 expression, monocyte chemotactic protein-1 production, and fluorometric detection of superoxide and hydrogen peroxide production decreased, whereas a concomitant increase in NO production was noted (all P < 0.01). Additionally, both monocyte adhesion (P < 0.05) and MCA (P < 0.01) decreased. Nine of 15 were no longer positive for metabolic syndrome postintervention. Intensive lifestyle modification may ameliorate novel coronary artery disease risk factors in men with metabolic syndrome factors before reversal of obesity.
- atherosclerosis
- lipids
- cell adhesion molecules
- nitric oxide
- matrix metalloproteinase-9
atherosclerotic disease is the leading cause of mortality in developed countries, with coronary artery disease (CAD) being the number one killer of both men and women. Early epidemiological and clinical studies established a link between dietary saturated fat and cholesterol, serum cholesterol, and CAD mortality (28). The Framingham Heart Study and Multiple-Risk Factor Intervention Trial Study emphasized the relationship between serum cholesterol, especially low-density lipoprotein cholesterol (LDL-C), and CAD (9). Although serum lipid levels have been the focus to explain the incidence of atherosclerosis, other risk factors such as oxidative stress, inflammation, endothelial cell activation, platelet activation, and plaque stability are important. For example, levels of the oxidative stress markers 8-isoprostaglandin F2α (8-iso-PGF2α) (42) and myeloperoxidase (MPO) (7), inflammation-associated proteins C-reactive protein (CRP) and soluble intracellular adhesion molecule (sICAM)-1 (48), soluble P-selectin (47), and the matrix metalloproteinase MMP-9 (17) all independently predict early risk of cardiovascular disease or myocardial infarction.
Diet and exercise modifications have been documented to ameliorate the classic CAD risk factors, including hyperlipidemia, hypertension, and insulin resistance (49). The clustering of multiple CAD risk factors in the same individual, commonly referred to as the metabolic syndrome, is extremely prevalent in Westernized societies, affecting ∼23% of the population and ∼43% of those above 60 years of age (20). Accordingly, the examination of the effect of modifying environmental influences (e.g., diet, physical activity, cigarette smoking) is warranted. The present study was designed to investigate the hypothesis that a combined intervention consisting of a high-fiber, low-fat diet and physical activity confers reductions in oxidative stress, inflammation, and monocyte-endothelial interactions in obese men at high risk for CAD and related clinical outcomes.
Diet and Exercise Intervention
The study protocol was approved by the Human Subjects Protection Committee of the University of California, Los Angeles, and informed consent of all participating subjects was obtained. Serum samples for this study were obtained from 31 overweight/obese middle-aged and older men (age range 46–76, mean 63.3 yr) who voluntarily participated in the Pritikin Longevity Center 21-day residential diet and exercise intervention during 2001. All participants were overweight or obese [mean body mass index (BMI) = 33 ± 1.5], and 15 had the metabolic syndrome according to the World Health Organization modified criteria (32). There were 13 Type 2 diabetic patients (by fasting glucose); all others had >1 metabolic syndrome factor and five had diagnosed CAD. All subjects were free of any viral infections and were able to consume the prescribed diet and to perform physical activity.
Once enrolled in the program, participants underwent a complete medical history and physical examination, followed by a 21-day diet and exercise intervention as previously described (50). From dietary analysis software, prepared meals contained 12–15% of calories from fat (polyunsaturated-to-saturated fatty acid ratio 2.4:1), 15–20% of calories from protein, and 65–70% of calories from primarily unrefined carbohydrate, high in dietary fiber (>40 g per/day). The program is designed to allow the subjects ad libitum eating without control of calories, only restricting the type of foods. Carbohydrates were primarily in the form of high-fiber whole grains (≥5 servings/day), vegetables (≥4 servings/day), and fruits (≥3 servings/day). Protein was from plant sources, nonfat dairy (up to 2 servings/day), and fish/fowl (3 oz. portions 1 day/wk and in soups or casseroles 2 days/wk).
Before starting the exercise training, subjects underwent a graded treadmill stress test according to a modified Bruce protocol to determine the appropriate individual level of exercise intensity. On the basis of the results, the subjects were provided with an appropriate training heart rate value and given an individualized walking program including both level and graded walking. The exercise regimen consisted of daily treadmill walking at the training heart rate for 45–60 min. The training heart rate was defined as 70–85% of the maximal heart rate attained during the treadmill test.
Twelve-hour fasting blood samples were drawn from the subjects in Vacutainers (Becton-Dickinson Vacutainer Systems) containing SST clot-activating gel between 6:30 and 8:00 AM on days 1 and 21 of the intervention. The blood was transported on ice to the laboratory, and the serum was separated by centrifugation and stored at −80°C until analyzed. Weight was measured by using a scale from Pennsylvania Medical Scales (model no. 7500). Height was measured with a stadiometer from Seca, attached to the wall. BMI was calculated as weight (kg)/height (m2).
Determination of Serum Lipids, Glucose, Insulin, Homeostasis Model Assessment, and Quantitative Insulin-Sensitivity Check Index
Total cholesterol (total-C), triglycerides (TG), and HDL-C levels were measured using a kit from Sigma Diagnostics (St. Louis, MO). The LDL-C was calculated as described by Friedewald et al. (21). Glucose concentration was determined by use of standard enzymatic procedures on an Olympus Autoanalyzer (Quest Diagnostics). Fasting insulin concentration was measured by radioimmunoassay (Diagnostic Systems Laboratories). Insulin resistance was evaluated by homeostasis model assessment (HOMAIR), which has been shown to correlate with insulin sensitivity by the hyperinsulinemic-euglycemic clamp (31). HOMAIR is calculated as [fasting insulin (μU/ml) × fasting glucose (mmol/l)]/22.5. Quantitative insulin-sensitivity check index (QUICKI) is determined from a mathematical transformation of fasting blood glucose and plasma insulin levels and has been shown be to a surrogate for insulin sensitivity that correlates well with the minimal model and the hyperinsulinemic-euglycemic clamp (26). QUICKI = 1/{log[fasting insulin (μU/ml)] + log[fasting glucose (mg/dl)]}. Because QUICKI is the reciprocal of the log-transformed product of fasting glucose and insulin, it is a dimensionless index without units.
Oxidative Stress Measures
Serum MPO concentration was measured in duplicate with an ELISA kit (Calbiochem) according to the manufacturer's instructions. Serum 8-iso-PGF2α was measured in duplicate using an enzyme immunoassay kit (Cayman Chemical).
Determination of Serum CRP, sICAM-1, Soluble P1-Selectin, Macrophage Inflammatory Protein-1α, and MMP-9
Serum CRP (Diagnostic Systems Laboratories), sICAM-1 and soluble P-selectin (sP-selectin), macrophage inflammatory protein-1α (MIP-1α; Biosource), and MMP-9 (R&D Systems) concentrations were measured in duplicate with specific ELISA kits according to the manufacturer's instructions.
In Vitro Cell Culture Studies
Human aortic endothelial cells (HAEC) alone and HAEC and human aortic smooth muscle cells (HASMC) were cocultured as previously described (40, 52). In brief, the cells were subcultured by trypsinization and grown to confluence in 75 cm2 flasks in M199 medium (Invitrogen) supplemented with 20% vol/vol FBS, 0.8 ml heparin, and 2 mg endothelial cell growth factor/100 ml media (Becton-Dickinson); 1% vol/vol penicillin-streptomycin-glutamine (GIBCO-BRL); and 1% vol/vol sodium pyruvate (GIBCO-BRL). HASMC were cultured in the same media without addition of endothelial cell growth factor or heparin. Subsequently, wells in a 96-well plate were treated with 0.1% gelatin for at least 1 h. HASMC were seeded in the wells at a density of ∼5 × 104 cells/cm2 and were cultured for 2–3 days at 37°C, 95% O2-5% CO2, at which time they had reached confluency. For cocoltures, HAEC were subsequently overlaid on top of HASMC at ∼1 × 105 cells/cm2 and were allowed to grow forming a complete monolayer of confluent HAEC in 2 days.
Production of monocyte chemotactic protein-1.
Cocultures were washed with M199 medium containing 1% FBS three times. The second wash was incubated for 1–2 h at 37°C and 95% O2-5% CO2; other washes were removed immediately. Washed cocultures were then incubated with M199 medium containing 5% human serum pre- and postintervention for 4 h. Subsequently, cultures were centrifuged and culture supernatants harvested and stored at −20°C pending the monocyte chemotactic protein-1 (MCP-1) measurement by ELISA (PharMingen, BD OptEIA ELISA set no. 555179) following the manufacturer's instructions. Serum samples were incubated in wells with no cells as a control. Endothelial cell production of MCP-1 was determined by subtracting no-cell control supernatants from supernatants incubated with cocultures. All tests were run in triplicate.
VCAM-1 expression.
A modified ELISA procedure was used to measure cellular VCAM-1 content (44). HAEC were grown to confluency in 96-well plates. Cultures were then washed three times in media containing 1% FBS. The second wash was incubated for 1–2 h at 37°C, 95% O2-5% CO2. Other washes were removed immediately. Washed cultures were then incubated with media containing 10% preintervention or postintervention serum for 4 h. After incubation, supernatants were removed and HAEC were washed once with 200 μl of PBS, fixed in 150 μl of 100% methanol for 10 min, air dried, sealed, and stored at 4°C. Dried cells were rehydrated and blocked in 200 μl of PBS containing 0.1% Tween-20 and 0.5% BSA (PBS-Tween-BSA) for 30 min and then washed twice in PBS-Tween. HAEC were then incubated for 2 h at room temperature with a mouse monoclonal IgG antibody against human VCAM-1 (PharMingen cat. no. 555645) diluted 1:500 in PBS-Tween-BSA. The wells were then washed twice in PBS-Tween, followed by incubation with a horseradish peroxidase-conjugated secondary antibody against mouse IgG from sheep (Amersham Life Sciences cat. no. NA931V) diluted in PBS-Tween-BSA at a 1:1,000 dilution. After a 1-h incubation at room temperature, wells were washed five times in PBS-Tween, and they were subsequently colored with 100 μl of tetramethylbenzidine reagent (Sigma cat. no. T0440) as substrate for the bound horseradish peroxidase. After 5 min of incubation, the reaction was stopped by adding 100 μl of 3 M H2SO4. Absorbance was read at 450 nm. FBS (10%) was used as a control and 10 ng/ml LPS was used as a positive control. The data are expressed as percentage of FBS control.
Nitric oxide production.
All steps involving the fluorescent probe were performed without direct light. The average of quadruplicate values for each condition was then taken and the final values for each test condition reported as a percentage of FBS control. The cell-permeable fluorescent probe 4,5-diaminofluorescein diacetate (DAF-2DA, Calbiochem) was used to measure nitric oxide (NO) production by HAEC (37). DAF-2DA is converted to DAF-2 by intracellular esterases, trapping the probe inside the cell. DAF-2 reacts with NO to form the highly fluorescent compound DAF-2T. After the HAEC in 96-well plates reached confluency, growth medium was removed and the cells were washed with 200 μl serum-free medium (SFM) three times. The second wash was incubated for 1 h at 37°C and 95% O2-5% CO2. SFM supplemented with 10% test serum (pre- or postintervention) was added onto cells that were then incubated at 37°C and 95% O2-5% CO2 for 18 h. Thereafter, 100 μl of 10 μM DAF-2DA dissolved in SFM was added to all cells except negative control wells. Negative control wells included cells with 100 μl of SFM containing either 10 μM 4 AF-DA (Calbiochem), a nonreactive DAF-2DA analog, or 300 μM N-nitro-l-arginine methyl ester (l-NAME, Sigma), an inhibitor of NO synthesis. The cells were then placed in a light-protected incubator at 37°C and 95% O2-5% CO2 for 1 h. After incubation, cells were washed three times with 200 μl of SFM to remove any residual extracellular DAF-2DA probe. Subsequently, 100 μl of SFM with 4 μM bradykinin (Calbiochem) was added to the cells. The DAF-2DA positive control included DAF-2T (Calbiochem) dissolved in SFM. After 10–15 min in a light-protected incubator at 37°C and 95% O2-5% CO2, fluorescence intensity was read and quantified in a fluorescence microplate reader at 495-nm excitation wavelength and 515-nm emission wavelength. The optical density (OD) readings pre- and postintervention were expressed as percentage of FBS control. Pictures of the DAF-2T fluorescence in the HAECs from the representative pre- and posttest conditions were taken with a camera connected to a fluorescent microscope (Zeiss Axiovert 135 microscope) and a computer, using Axiovision software. Picture (black and white) location within each well was standardized through finding a cluster of cells indicated by a dark spot at the center of each well with low magnification (×10). A higher magnification (×20) and light wavelength filter were then used to identify the intracellular fluorescence of a group of cells within this cluster. The filter allowed the view of light only within the same wavelength range as the light emitted by the fluorescent probe. The color corresponding to the same wavelength was added to the black and white picture using Axiovision software. The picture files were converted to JPEG format using Adobe Photoshop.
Hydrogen peroxide production.
The cell-permeable fluorescent probe 2′,7′-dichloro-dihydrofluorescein (DCF) diacetate (DCFH-DA, Molecular Probes) was used to measure hydrogen peroxide production by HAEC (10). For DCFH-DA to emit a fluorescent signal the diacetate group is first cleaved by cytoplasmic esterases to form DCFH. DCFH reacts with hydrogen peroxide to form a highly fluorescent compound, DCF, that can be used to detect enzymatic generation of reactive oxygen species (ROS) (4). In cultured endothelial cells, DCF is oxidized by hydrogen peroxide, along with other intracellular processes involving ROS, making it useful in determining changes in hydrogen peroxide and overall oxidant formation (51). SFM supplemented with 10% test serum (pre- or postintervention) was added onto cells that were then incubated at 37°C and 95% O2-5% CO2 for 18 h. The hydrogen peroxide positive control included cells incubated for 18 h with 2 ng/ml TNF-α dissolved in SFM. After incubation, the supernatant was removed from the cells and 100 μl of 10 μM DCFH-DA dissolved in SFM was applied to the cells, which were then placed in a light-protected incubator at 37°C and 95% O2-5% CO2 for 1 h. After DCFH-DA incubation, cells were washed three times with 200 μl of SFM to remove residual extracellular probe. After being washed, 100 μl SFM was applied to the cells, which were then placed in a light-protected incubator at 37°C and 95% O2-5% CO2 for 30 min, allowing time for the intracellular probe to be cleaved and oxidized as described above. The DCFH-DA probe positive control included the fluorescent oxidized form of DCFH in SFM. The negative control included SFM on cells without any probe application. The fluorescence intensity was then read and quantified in a fluorescence microplate reader with 485-nm excitation wavelength, 530-nm emission wavelength, and 515-nm cutoff. The OD readings pre- and postintervention were expressed as a percentage of FBS control.
Superoxide production.
The cell-permeable fluorescent probe dihydroethidium (DHE, Calbiochem) was used to measure superoxide production by HAEC (53). DHE has blue fluorescence and after DHE is oxidized to ethidium by superoxide it intercalates with the cell's DNA staining the nucleus a bright fluorescent red. SFM supplemented with 10% test serum (pre- or postintervention) was added onto cells, which were then incubated at 37°C and 95% O2-5% CO2 for 18 h. The superoxide positive control included cells incubated with 2 ng/ml TNF-α dissolved in SFM. After incubation, the supernatant was removed and 100 μl of 25 μM DHE dissolved in SFM was applied to the cells, which were then placed in a light-protected incubator at 37°C and 95% O2-5% CO2 for 45 min. After DHE incubation, cells were washed once with 200 μl of SFM and then twice with 200 μl of HEPES to remove residual extracellular probe. After being washed, 100 μl of HEPES were applied to the cells, which were then placed in a light-protected incubator at 37°C and 95% O2-5% CO2 for 10 min. The negative control included HEPES buffer without any probe application. The fluorescence intensity was then read and quantified in a fluorescence microplate reader. A 518-nm excitation wavelength and 605-nm emission wavelength with 590-nm autocutoff filter were used to detect and quantify the fluorescence of the probe that reacted with superoxide. A 355-nm excitation wavelength and 425-nm emission wavelength with 420-nm autocutoff filter were used to detect and quantify the fluorescence of the remaining probe that did not react with superoxide. The average of the quadruplicate values was taken for each condition. The final data points were reported as a percent of the 10% FBS condition. Pictures of the ethidium fluorescence were taken in the same manner as for NO detection (above).
Monocyte adhesion assay.
Confluent monolayers of HAEC were grown and monocyte adhesion was quantified with adaptation of methods from Van Lenten et al. (52). HAEC were grown in gelatin-coated 48-well microtiter plates and were treated with pre- and postintervention serum (10% final concentration) in M199 media for 20 h. Supernatants were then removed and cultures washed with SFM. A 400-μl monocytic cell line (THP-1) suspension in M199 providing 2.0 × 105 cells/cm2 was then added per well. Extreme care was taken to avoid drying out of the HAEC during the changes and throughout the assay. The loosely adherent cells were washed off with PBS, the cultures fixed with 1% glutaraldehyde, and the adherent THP-1 cells enumerated under ×320 magnification. The preintervention and postintervention serum was compared with 10% FBS and 10 ng/ml LPS as a positive control.
Monocyte chemotactic activity assay.
Monocytes from healthy normal individuals were isolated by a modification of the Recalde procedure (18). The monocyte chemotactic activity (MCA) was performed as previously described by Navab et al. (40). Briefly, pre- and postintervention sera were added to confluent monolayers of HAEC. Eighteen hours later, supernatants were collected and tested for MCA as described previously (38). The supernatants were added to a standard Neuro Probe chamber (Neuro Probe, Cabin John, MD), with isolated human peripheral blood monocytes added to the top. The chamber was incubated for 60 min at 37°C. After the incubation, the chamber was disassembled and the nonmigrated monocytes were wiped off. The membrane was then air dried and fixed with 1% glutaraldehyde and stained with 0.1% crystal violet dye. The number of migrated monocytes was determined microscopically and expressed as the mean ± SE of 12 standardized high-power fields (HPF) counted in quadruple wells. Additionally, we confirmed that this assay is specific to monocytes and chronic inflammation, as opposed to neutrophils and acute inflammation, by measuring E-selectin after a 4 h incubation, which did not change (1).
Statistical Analysis
Statistical analyses were performed with GraphPad Prism version 4.0 for Windows, GraphPad Software (San Diego, CA), and STATA 9.0 (College Station, TX). Preintervention and postintervention values were compared by matched-pair t-tests. Correlations were tested on all available data by determining Pearson's correlation coefficients for the relationships between MPO, CRP, 8-iso-PGF2α, DAF-2A, ethidium and DCF fluorescence and BMI, body weight, fasting insulin, glucose, and HOMAIR. All data are expressed as means ± SE unless otherwise noted. A P value of <0.05 was considered statistically significant.
Fasting Lipids, Glucose, Insulin, Blood Pressure, and Anthropometry
Anthropometric and metabolic data are presented in Table 1, along with consensus values that the medical community considers normal. The 21-day diet and exercise intervention significantly reduced body weight (P < 0.01) and BMI (P < 0.01), although as a group the subjects remained obese (BMI > 30 kg/m2) at the end of the intervention. Subjects positive for metabolic syndrome by World Health Organization criteria decreased from 48 to 19%. Noted were significant reductions in total-C, LDL-C, HDL-C, TG, LDL-to-HDL ratio, and total-C-to-HDL-C ratio (P < 0.01 for all). Significant reductions in serum fasting glucose (P < 0.05) and fasting insulin (P < 0.01) were also observed after the intervention. The HOMAIR and QUICKI were determined as surrogates of insulin sensitivity. The intervention resulted in a significant decrease in HOMAIR (P < 0.01) as well as a significant rise in QUICKI (P < 0.01). Correlation analyses indicated that, except for a significant correlation between change in CRP and change in insulin (r = 0.52, P = 0.03), no significant correlation between changes in inflammation or oxidative stress measures and metabolic factors were noted.
Oxidative Stress Measures
After the diet and exercise intervention, the enzymatic oxidant MPO was significantly reduced (132.7 ± 11.2 vs. 166.2 ± 19.3 ng/ml, P < 0.05, Fig. 1A). Additionally, a significant reduction in serum 8-iso-PGF2α (131.3 ± 21.6 vs. 202.6 ± 37.2 pg/ml, P < 0.01, Fig. 1B) was observed.
Serum, CRP, sICAM-1, sP-selectin, and MMP-9
As noted in Fig. 2, after the intervention, there was a reduction in serum concentration of the inflammatory protein CRP (1.46 ± 0.29 vs. 2.39 ± 0.46 mg/l, P < 0.01, Fig. 2A). We measured the serum concentration of ICAM-1 and sP-selectin as indicators of vascular endothelial cell and platelet activation, respectively. Both ICAM-1 (291.2 ± 33.4 vs. 363.5 ± 45.0 ng/ml, P < 0.05, Fig. 2B) and sP-selectin (135.3 ± 5.6 vs. 147.5 ± 8.1 ng/ml, P < 0.01, Fig. 2C) concentrations decreased postintervention. Additionally, serum total level of the gelatinase MMP-9, an index of plaque stability, was reduced postintervention (625.7 ± 61.3 vs. 779.3 ± 85.2 ng/ml, P < 0.01, Fig. 2D).
Monocyte Adhesion, Chemotactic Activity, and MIP-1α
Monocyte adhesion using THP-1 cells, a monocytic cell line, significantly decreased after the intervention (127.7 ± 13.4 vs. 185.3.1 ± 12.5 adherent THP-1/HPF, P < 0.001, Fig. 3A). The ability of serum to induce MCA was tested by incubating pre- and postintervention serum with cultured HAEC. Supernatants from these incubations revealed a significant reduction in MCA (11.1 ± 1.1 vs. 16.5 ± 1.3 migrated monocytes/HPF, P < 0.01, Fig. 3B). The chemokine MIP-1α also decreased postintervention (8.93 ± 1.7 vs. 12.6 ± 1.8 pg/ml, P < 0.05, Fig. 3B), corroborating the drop in MCA.
In Vitro Production of MCP-1, VCAM-1, Superoxide, Hydrogen Peroxide, and NO
In an effort to identify specific factors to account for the observed reductions in THP-1 adhesion and chemotaxis, endothelial cell production of MCP-1, VCAM-1, ROS, and NO were investigated. When pre- and postintervention sera were added to cultured HAEC for 4 h, the expression of the adhesion molecule VCAM-1 was reduced (97.0 ± 5.1 vs. 113.8 ± 7.6% of FBS control, P < 0.01, Fig. 4A). We determined the production of MCP-1 in a coculture of HAEC and HASMC as an index of monocyte chemoattraction. Moreover, the addition of postintervention sera to cocultures of HAEC and HASMC for 4 h resulted in a lower production of MCP-1 compared with that noted with preintervention (62.4 ± 3.8 vs. 68.0 ± 3.7 ng/ml, P < 0.05, Fig. 4B).
The probe DCF was used as an index of ROS production, primarily as hydrogen peroxide. Postintervention, there was a significant reduction in DCF fluorescence compared with preintervention, indicating a decrease in hydrogen peroxide formation (105.4 ± 5.8 vs. 114.2 ± 7.4%, P < 0.01, Fig. 5A). \. Medium plus TNF-α (2 ng/ml) induced hydrogen peroxide production (119 ± 3.0% of the FBS control). DHE was used to detect superoxide production in HAEC incubated with subject sera. The ethidium fluorescence, an indicator of reacted DHE, decreased significantly postintervention (84.5 ± 4.8 vs. 92.0.2 ± 4.5%, P < 0.01, Fig. 5B). These data demonstrate decreased subject sera-stimulated ROS generation by HAEC. Finally, incubation of subject sera with cultured HAEC in concert with use of the fluorometric probe DAF-2DA was used to detect NO production. DAF-2T quantitated fluorescence, increased significantly as a percentage of FBS control postintervention vs. preintervention (132 ± 5 vs. 144 ± 5% of FBS control, P < 0.01, Fig. 5C), indicating increased NO production from HAEC grown in postintervention serum. Coincubation of DAF2-DA with AF-DA or l-NAME abrogated NO production (data not shown).
Current recommendations to reduce the risk of CAD include lifestyle modification (exercise and diet), which may have significant benefit in the prevention and treatment of CAD (49). The Adult Treatment Panel III guidelines included recommendations for therapeutic lifestyle change, including diet and physical activity (16). Hence, the present study was designed to investigate the effects of a short-term, intensive diet and exercise intervention on several aspects of atherogenesis in men with metabolic syndrome factors. The primary findings of this study provide evidence that, in men with metabolic syndrome, lifestyle may 1) improve the lipid and metabolic profile, 2) decrease oxidative stress and increase NO production, 3) decrease inflammation, 4) decrease endothelial cell activation and platelet activation, 5) decrease monocyte adhesion and MCA, and 6) decrease MMP-9, a marker of plaque destabilization.
For the first time, we noted a significant decrease in THP-1 cell adhesion to endothelial cell cultures incubated with postintervention serum. This was likely due in part to the reduction in serum-stimulated VCAM-1 expression, serum ICAM-1, and sP-selectin. P-selectin is a cell-surface adhesion molecule involved in leukocyte rolling and attachment as well as platelet activation (36), and thus the reduction in sP-selectin also reflects a reduction in platelet activation. We also noted a decrease in MCA in HAEC after the diet and exercise intervention. The decrease in MCA was confirmed by a reduction in MCP-1 production in a HAEC/HASMC coculture, because MCA is directly related to MCP-1 production (40). Additionally, the decrease in MIP-1α, a chemoattractant that activates monocytes (45), supports the contention that monocyte attraction was mitigated by the intervention. The effect of postintervention serum on HAEC could be due, in part, to increased antioxidant capacity, decreased LDL oxidation, and/or reduced LDL substrate, resulting in less endothelial cell activation.
Atherosclerosis is not only a disease of lipid accumulation, but also a chronic inflammatory process (5), and inflammation is now considered to be a component of the metabolic syndrome (56), with CRP being a well-established promoter of atherogenesis. The present study demonstrated a marked reduction in CRP (∼40%) within 3 wk, a finding likely unrelated to CRP instability (41) or circadian variation (33). Our laboratory previously reported (54) a reduction in CRP in women after the same diet and exercise intervention, as have other groups using caloric restriction (25) or diet and exercise (57). Receptor-mediated CRP uptake is associated with decreased nitric oxide bioavailability in human endothelial cells (13) and induces plasminogen activator inhibitor (14). The observed increase in NO production and/or decrease in ROS may be related to the reduction in CRP. Epidemiological studies (19) suggest that regular physical activity is associated with reduced inflammation, and Liu et al. (35) have shown that glycemic load is associated with increased plasma CRP concentration.
Vulnerable plaques tend to have a lipid-rich core, with a thin fibrous cap and reduced extracellular matrix and extensive macrophage-derived foam cells that produce MMP enzymes that degrade the collagen and elastin components of the matrix. Recent data suggest that MMPs play an integral role in human atherosclerosis and plaque disruption, because patients with CAD and history of myocardial infarction have elevated MMP-9 serum levels (17, 46). The decreased total MMP-9 postintervention is in agreement with the reduction in oxidized lipids, which have been shown to upregulate MMP-9 expression in monocyte derived macrophages (55). Previously Koh et al. (30) investigated the effects of diet and simvastatin on MMP-9 levels and noted that whereas an National Cholesterol Education Program Step I diet for 14 wk (reduced cholesterol about ∼10%) had no effect on MMP-9 levels, addition of simvastatin led to a reduction in MMP-9.
One potential enzymatic source for generation of NO-derived oxidants is MPO, a hemoprotein abundantly expressed in neutrophils, and to a lesser extent by monocytes and macrophages, that displays potent proatherogenic properties. MPO can oxidize LDL-C, thereby propagating its uptake by macrophages and perpetuating foam cell formation (43). MPO is markedly increased within human atherosclerotic lesions (12) and directly utilizes both NO and nitrite as substrates in vitro (15) and participates in both protein nitration and initiation of lipid peroxidation in vivo (8). The decrease in MPO with lifestyle modification provides evidence for a decrease in oxidative stress, data that agree with our laboratory's previous documentation of a reduction in 8-iso-PGF2α (50), which we also confirmed. Interestingly, MPO has been shown to activate MMPs and promote destabilization and rupture of the atherosclerotic plaque surface (22). Thus the reduction in MMP-9 in this study may be mediated, in part, by the reduction in MPO.
We utilized a HAEC culture system and specific fluorescent probes to study subject sera-stimulated NO and ROS production. Both DCF and ethidium fluorescence decreased postintervention, indicating reduced serum-stimulated production of peroxides and superoxide, respectively. As determined by DAF2-DA fluorescence, we noted increased NO production by HAEC in vitro in agreement with previous data documenting improved urinary NO metabolite excretion with lifestyle intervention (50). Additionally, Hamdy et al. (24) noted increases in both insulin sensitivity and flow-mediated dilation in subjects with impaired glucose tolerance and diabetes. Both DCF and ethidium fluorescence decreased postintervention, indicating reduced serum-stimulated production of peroxides and superoxide, respectively. It is plausible that the improvement in endothelial function noted by others (11, 23) with diet and/or exercise was due, at least in part, to increasing endothelial cell NO production, decreased NO-scavenging ROS production, and/or MPO levels, which vary inversely with endothelial dysfunction (2).
The present study has important strengths and limitations that need to be acknowledged. The major strength is the supervised nature of the study. Supervising food intake and physical activity removes the need to question compliance or to rely on food intake and activity questionnaires. Furthermore, all exercise sessions were supervised and adherence to the diet and activities was essentially 100%. Conversely, the study was not randomized and the subjects were motivated to take part in the intervention; hence, we cannot extrapolate adherence to the general population. Nevertheless, the findings document that benefits are possible in motivated subjects. Caloric intake was not determined with consumption of the ad libitum diet, except for animal protein. However, increasing fiber and reducing the fat content of the diet without specific efforts to maintain body weight has been reported to result in a spontaneous decrease in caloric intake and weight loss (27, 34). Finally, more sophisticated measures of insulin sensitivity such as an oral glucose tolerance test may be more definite than surrogate measures of insulin sensitivity used in our analysis. It is possible that we underestimated the number of diabetic subjects because we did not perform oral glucose tolerance tests.
In conclusion, multiple factors can modulate atherosclerotic lesions, and little is known about the effects of lifestyle modification on novel mediators of the atherosclerotic process. Implementation of a high-fiber, low-fat diet, combined with daily aerobic exercise, results in significant reductions in serum lipids, insulin, oxidative stress, inflammation, leukocyte-endothelial interactions, adhesion and MCA, and leukocyte production of MMP-9. The reduced monocyte adhesion and MCA observed when using the serum after the intervention is a clear indication of increased antioxidant-oxidant balance (39). The changes observed appear to be largely independent of weight loss, as the magnitude of weight loss was minimal (107 to 104 kg, mean BMI change 1 unit), the subjects remained overweight/obese at the conclusion of the study. Furthermore, correlational analysis showed no significant relationship between change in BMI or body weight and any of the parameters measured. These observations suggest that an appropriate diet and daily exercise may confer significant risk reduction despite relatively minimal weight loss. Blair and Brodney (6) have suggested that cardiorespiratory fitness may be a more powerful predictor of risk than body weight per se. We suggest that the focus for CAD risk reduction be emphasized through ameliorating metabolic risk as opposed to focusing on body weight changes. An intervention of this type may be of clinical benefit for those desiring rapid cardiovascular risk reduction. Additionally, the changes in selected diabetic-related variables appear to be superior to changes noted with metformin treatment (29), furthering the notion that lifestyle may provide an alternative to traditional drug treatment. The impressive response observed in a relatively short period has been documented to be durable in its effects (3) and highlights the value of intensive lifestyle modification in men at high risk for CAD, which if sustained may mitigate the progression of atherosclerosis and its clinical consequences.
This study was supported by a grant from the LB Research and Education Foundation. Christian Roberts was supported during this project by a National Research Scholarship Award postdoctoral fellowship, National Heart, Lung, and Blood Institute F32 HL-68406-01.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Copyright © 2006 the American Physiological Society


text:
Has anyone else noticed that almost every time there is a big global warming "summit" that God seems to be mocking the lefties with extream winter weather? I noticed this long before the current Copenhagen cap & tax summit, but here we are again...Copenhagen is having a blizzard at exactly the same time as this fiasco is going on.
I heard on the radio that it hasn't snowed in Copenhagen for 14 years but I haven't been able to confirm that. If that were the case, I'd love to know for sure, as that would be pretty undeniably God.
Whether it's snowed in Copenhagen for the last 14 years or not, I do believe God is mocking Al Gore and the whole "climate change" religion, and I love it.

subset: commoncrawl


text:
Go for a dramatic look at your next formal event wearing this cocktail dress from Allure 6660. This modern dress has an asymmetrical neckline with a feather detail at one shoulder. A sweetheart shape accents a portion of the bust. Paisley print swirls throughout the dress with a metallic finish that lends a glamorous feel to the look. This dress has a mini hemline. Make a splash in this unique dress.
Please refer to our return policy.
We are an authorized retailer of all the dresses we sell. We only sell 100% authentic dresses.
Find a lower price and we will match and beat it by 5%
Free shippingFree ground shipping on orders over $50.
Free shipping
Free ground shipping on orders over $50.
Click to get estimated price in different currancy
Copyright ©2008-2017, NewYorkDress.com. All Rights Reserved.
Terms & Conditions | Privacy Policy


text:
Jack Ingram
Close enough
(Lucky Dog/Sony Nashville)
It might not be fair to blame Jack Ingram for such acts as the execrable Pat Green or a thoroughly unoriginal and clichéd newcomer like Adam Carroll, but as one of the originators of the post- Robert Earl Keen syndrome, Ingram has definitely helped pave the way for other good ol' young guys with guitars. Rising out of the Dallas bar scene with a number of self-released discs that sold many thousands of copies, Ingram didn't exactly seem like an original talent at first and even second glance. But with a strong likability factor and a canny ability to work his way upward through the system from the outside, Ingram has earned himself one and now two deals with Nashville major-label imprints, this time out on Sony's Lucky Dog label, which also records such Texan peers of Ingram's as Bruce and Charlie Robison.
Hey You isn't the arresting sort of album that such a title might imply, but it is Ingram's best effort to date. And "effort" is a fairly accurate description of one of Ingram's major musical charms. You can't help but like a guy who's sincerely trying to make music of merit, even if Hey You is basically just a solid and enjoyable collection of quality Texas country-rock. Rather than begging the Keen comparisons of Ingram's past, this disc sounds more like a Steve Earle album than did the one Earle actually produced for Ingram, 1997's Livin' or Dyin'. No doubt some of that vibe is instilled by producer Richard Bennett -- who has co-produced Earle -- and the fact that Ingram happens to sing just like Earle. Not that any of that is necessarily a bad thing, especially as Ingram makes it all sound like admiration and homage rather than shameless imitation.
Jack Ingram may not be the strongest or most distinctive singer, and he has yet to write a song that's either undeniably catchy -- his snappiest tune remains the Colin Boyd-penned "Flutter" -- or truly inspiring. But once again, his artistic solidity counts for more than you might think. Wise enough to use co-writers whose writing ability is a few notches above his own -- guys like Jim Lauderdale, Todd Snider, Bruce Robison, and Tom Littlefield -- Ingram has come up with a collection of darn good, if not exactly great, songs here (including his two solo compositions, "Biloxi" and "Inna From Mexico"). He sings them with sincerity and commitment, and the whole vibe of this album is definitely the sort of stuff Nashville should be trying to get on the charts instead of the young-country crud they are currently pimping. In a time and genre in which there's little that falls between greatness and dismissible mediocrity (and worse), Hey You rates Ingram a pat on the back for trying his best. It may only be good, but at least it's good enough.
If you like this story, consider signing up for our email newsletters.
You have successfully signed up for your selected newsletter(s) - please keep an eye on your mailbox, we're movin' in!
Rob Patterson


text:
Oda Myers
Found 10 Records, 9 Photos and 2,350,719 Family Trees
Born in Texas, USA on Jun 1893 to Brantley Grover Myers and Lula Ann Ward.
Family Members
Ready to discover your family story?
Simply start with yourself and we'll do the searching for you.
Potential photos and documents for Oda MyersView All 9 Images
Top record matches for Oda Myers
Surname meaning for "Myers"
English (mainly Yorkshire): patronymic from


text:
UNION, N.Y. – The parents of the man who gunned down 13 people at an upstate New York immigration center have put their house up for sale.
Neighbors tell The Binghamton Press & Sun-Bulletin that Henry Voong and Mui Thong have moved to Florida.
Click here for photos.
Jiverly Wong was living with his parents when he went on the rampage April 3 at the American Civic Association in Binghamton, killing 11 immigrants in an English class, a teacher and a receptionist before committing suicide. Police believe 41-year-old Wong, an immigrant from Vietnam and former center student, was angry over losing a job and frustrated by his poor English-language skills.
The parent's house in the town of Union is listed on the Greater Binghamton Realtor Web site for $63,000.


text:
RetroSound R-352N
2006 Pontiac Solstice
Crutchfield Customer Review (What's this?)
Easy to install Sounds great
Pros: Sounds great so easy to install
Cons: None
Our experts help you pick the ideal gear for your needs.Meet our advisors
Free tech support for the life of your gear.Read about our one-on-one expert help
You may return items that are complete and like new for any reason within 60 days.See the details of our return policy
Earn one point for every dollar you spend and use those points to save on future purchases.Get full details on Crutchfield Rewards
With most stereo and speaker purchases, we offer installation guides, dash kits, wiring harnesses, and speaker accessories at deep discounts. Also, you can just buy our installation guides for $10. (If you buy a new stereo or speakers from us within 60 days, we'll apply the $10 to your order.)Learn more
Our customers have trusted us with their business, and they've helped us win awards for our service.Check out our most recent awards
The manufacturer's warranty always applies.See more details
Our experts help you pick the ideal gear for your needs.Meet our advisors
Free tech support for the life of your gear.Read about our one-on-one expert help
You may return items that are complete and like new for any reason within 60 days.See the details of our return policy
Earn one point for every dollar you spend and use those points to save on future purchases.Get full details on Crutchfield Rewards
We offer vehicle-specific installation instructions, dash kits, wiring harnesses, and speaker accessories at deeply discounted prices with car stereo and speaker purchases. Available for most vehicles.Learn more
Our customers have trusted us with their business, and they've helped us win awards for our service.Check out our most recent awards
The manufacturer's warranty always applies.See more details
Item # 068R352N | MFR # R-352N
In Stock
Our VA-based experts can help.
Chat Email
RetroSound makes it easy to replace the factory speakers in almost any classic, vintage, or even new car. Their RetroMod Series speakers feature extremely shallow baskets designed to fit into a wide variety of standard speaker locations. They may look old school, but RetroSound builds their speakers from the ground up, using the latest techniques and materials.
Each R-352N 3-1/2" speaker features a sturdy polypropylene woofer with a Santoprene surround that delivers strong performance while standing up to heat and humidity. The Mylar dome tweeter broadcasts detailed highs without sounding shrill, and its low profile helps increase installation options.
Although efficient enough to play well with a factory radio, you can also power these RetroMod speakers with an amplifier to deliver your music with plenty of impact. Replace your wornout old 3-1/2"s with these updated RetroSounds, and your tunes will sound new again, just like your classic ride.
Average Customer Review(s):
Easy to install Sounds great
Pros: Sounds great so easy to install
Cons: None
These are not good. Sound is average at best and quality is poor. One speaker actually fell apart; the magnet came apart from the speaker housing. I'm not a pro, but have installed my share of stereos over the years, and I've never seen that. By selling this brand and even recommending them, Crutchfield is compromising their reputation.
Pros: The fit.
Cons: Poor sound and poor build quality.
I bought these RetroSound speakers to replace the so-so Boston Acoustic speakers in my front dash. The BA speakers used a small polypropylene cone as "tweeters" (really??), though with larger magnets and power handling than the basic stereo option. So naturally, these 2-way RetroSound speakers sounded better, crisper highs and with Bass Blocker filter (think I had 300hz or 500hz) warm, undistorted mids (don't want singers sounding like pitchy robot-aliens). But after nearly a year, one of the magnets came off a speaker. Since it wasn't wired to anything else, I was able to reattach the magnet to the speaker after cleaning up what appeared to be only a few craft glue-gun drops of glue used to assemble it at the factory. Since then that particular speaker distorts sound above low-medium volumes, and especially is distorted from that particular speaker during voice-command prompts and Bluetooth phone calls, even after I swapped left & right speakers to test connections and isolate that it's a speaker unit issue.
Pros: Good crisp highs and smooth mids when used with Bass Blockers to filter out the low bass signals from your upgraded stereo systems.
Cons: RetroSound speaker construction is poor: magnets were barely held on to speaker housing with a few drops of cheap glue. Just after a year in my sedan, I had to reattach the magnet with better glue and electrical tape. But since the magnet first fell off, which caused rattling and near complete cut-out of sound from that speaker, sound gets distorted above low volumes, it physically rattles, and sound is distorted half the time, leading me to believe the rest of the speaker is coming apart.
I have bought this speaker 2 times as oem replacement. Quality is way below my expectation. The 2nd pair is less than 8 months old and is experiencing heavy distortion after less than 1/2 hour my new jvc is on even with low volume. I had to the metal bracket to make it fit and close the cover. The speakers stick out enough where I can't fully tighten the screw on the dash covers. I'm looking again for higher end quality speakers but has not found a replacement. For sure not buying this speaker again. It's a shame Crutchfield are not testing this speaker for fitment and finish on a VW rabbit like my pickup. They would have known there's a problem with quality with either fit and durability and sound quality. For the price of this pair of speakers, not worth it.
Pros: Better than nothing.
Cons: All the things I stated in my review pertain to what's wrong with this speaker. Made cannot expect much from a Made in China speakers like this pair Retrosound R352N speakers I purchased twice not realizing the 2nd purchase were for the same low quality speakers.
Excellent Fitment; (Limited Depth); However, sound quality poor.
Pros: Excellent Fit w/ minimum depth clearance
Cons: Poor Sound Quality
For the price and the size excellent
Pros: Good sound, Fitt perfect
Cons: None
I bought these speakers due to size constraints and was expecting better quality but I was mistaken. The speakers look good when you open the box but after they were installed you can hear distortion and cracking all the time while they are playing. I will never recommend or buy another of their products.
Pros: None
Cons: Horrible sound quality
I bought these 3.5" Two-Ways as a replacement for my in-dash speakers on my 1987 Chrysler Fifth Avenue. I would to first say the speakers sound incredible! They really sound so much better than the factory speakers. You don't expect much from 3.5s but these really perform great. However, the fit is terrible. Yes, I understand fitting every vehicle is a challenge but I would never recommend these speakers unless you know they will fit properly. The problem is with the width of the frame not allowing the speaker to fit down into the speaker area of the dash. I had to make a modification to the dash in order for them to fit even remotely decent. Would I recommend them? No, I would not have spent the money to purchase them and kept the factory 3.5s in there. Alas, I made the best out of a bad situation. They do sound great even though I worry they do not fit properly and could "rattle" if my modification doesn't hold.
Pros: Incredible sound for a 3.5
Cons: Horrible fit, even for a low-profile 3.5
I ordered these in an effort to solve a problem with other aftermarket speakers being to deep and hitting the window when it was rolled down. For the most part it was a perfect fit, the low profile along with the provided bracket the install was clean. However the wiring directions are not detailed enough to explain what to do with the three wires on the factory harness, when, of course the new one only has two (+,-) If your not careful you will disable the tweeter also in the door if you wire it wrong. Overall very happy. Sound quality is good but remember there only 50 bucks, but a nice upgrade from the factory.
|Speaker Size
|3 1/2
|Tweeter Design
|Impedance (Ohms)
|Tweeter Composition
|Woofer Composition
|Woofer Surround
|Parts Warranty
|1 Year
|Labor Warranty
|1 Year
|Sensitivity (1W at 1 meter)
|Sensitivity at 2.83 volts
|Frequency Response
|100 - 21k Hz
|Minimum RMS Wattage
|Maximum RMS Wattage
|Peak Power Handling (Watts)
|Top-mount Depth (Inches)
|1 1/8
|Bottom-mount Depth (Inches)
|1 5/16
|Cutout Diameter or Length (inches)
|3 1/4
Woofer: The speakers feature poly cone woofers with Santoprene surrounds.
Tweeters: The tweeters are low profile Mylar domes.
At Crutchfield, you'll get detailed, accurate information that's hard to find elsewhere. That's because we have our own in-house Product Research team. They verify what's in the box, check the owner's manual, and record dimensions, features and specs. We stay on top of new products and technologies to help people make informed choices.
These speakers from Retrosound make it a lot easier to enjoy modern stereo sound in a pre-1960s vintage car or truck.


text:
Release Date: 2000 |
Album Rating: 3.5great album amazing movie hey guys
Beast review, so pos. I actually like this soundtrack a bit more than I like the film it goes with.
Album Rating: 3.5thanks bro, damn dude i thought the movie ruled hard, got me teary eyed and for a thrasher thats hard to do
Oh I agree, it's a damn good movie, Bjork's performance really moved me. Powerful stuff.
Shes is the beautifulest, fragilest and hottest person ever made.
"got me teary eyed and for a thrasher thats hard to do"
Album Rating: 3.5am i gay for being in touch with my emoticons? boys DO cry the cure were wrong!
shit maybe I'm gay for NOT being in touch with my emotions...ah fuk i never thought of that..
Sounds cool, am gonna doublebuy Homogenic and Medulla sometime soon, now that I'm no longer 100% obsessed with Post (what's Medulla like btw?)
Album Rating: 3.5medulla is a cappella, its pretty fuckin weird but it grows on you hard
i approve of that summary.
unban me
awesome review, pos
Album Rating: 3.5am i staff yet
love byurk so much she rules
staff now
Digging: Julien Baker - Turn Out The Lights
you are our unofficial staff, KILL
Album Rating: 3.51st line of this review is the truth, man!
The movie was freakin' soul-crushing! *whimper
pos'd with my
Bands: A B C D E F G H I J K L M N O P Q R S T U V W X Y Z


text:
Get a free shipping quote.
This guy has been hauled to many different places and is not spooky. You can ride him bareback. Easy to handle. No buck, spook, or rear. Has a partial blue eye. Very nice, safe horse. Will work cows and would be good for barrels or playdays. He is registered. Poco is a faster paced horse but he is not one of those that is constantly dancing sideways and running in place. He has a faster walk and is ready to go when asked. Will walk and go through anything.
Open spaces available for training and consignments...Located in College Station, Tx. Rates: $450/month boarding $550/month horse put on walker 3x week. Training: start to finish, problem horses, performance horses, and more (Call for rates) If you need a horse sold, we have the knowledge and skills to advertise and show your horse to potential buyers. Let us do all the work for you! 979-224-5586
Avoid Scams and Fraud - Potential areas of fraud: wire transfer, moneygrams, money orders, cashier checks, shipping, escrow, "transaction protection", "guarantee". Check out the Buyer Safety section for more info.


text: Holy corroded metal from alien acid blood, Batman! This is one of the biggest mods ever for a game and it's now available...for free. The game clocks in at a modest 242 megabytes, or a quarter of a gigabyte for you new-school gamers, and packs a massive punch by delivering Aliens-themed zeds and all your favorite weapons from the sci-fi horror franchise.


text:
At Gemvara, we believe that the jewelry you wear should be one of a kind, like you. That's why we make each piece to order, one at a time, just the way you want it. Choose Green Tourmaline and Yellow Gold or Rhodolite Garnet and White Gold: it's your choice. Mix and match gems and precious metals for a look that's exactly you. Gemvara uses only the highest quality materials to craft your November Birthstone Birthstone Jewelry $2,500 and Above design with meticulous attention to detail. Our precious metals are recycled or responsibly mined. Our wide selection of November Birthstone Birthstone Jewelry $2,500 and Above by talented designers means you can find jewelry that's exactly your style. You can also shop by style, choosing our Cocktail, Eclipse, or Flowers Collections. Gemvara's fine quality November Birthstone Birthstone Jewelry $2,500 and Above is designed to be passed down for generations to come, crafted by hand in the United States.
We can help right away. Chat with a jewelry expert now!


text:
This product is no longer available.
You can try these similar gifts instead.
Frank Lloyd Wright Taliesin Barrel Chair
A classic design made in Vermont with the Wright signature. The Taliesin Chair from 1911 was used in Wright's home in Spring Green, Wisconsin. Solid stained cherrywood and a red microsuede cushion.


text:
Camp Keyes
Maine Army National Guard Leader Lt.Col. Michael J. Backus Dies At Camp Keyes
Shock and sadness overspread Camp Keyes in Augusta this week with the unexpected passing of longtime Maine Army National Guard leader, Lt. Col. Michael J. Backus of Wilton. Backus died unexpectedly on Monday while performing duties at Camp Keyes.


text:
3 posts
How brilliant is that!
I looks more like a plastic cover you can buy?!
I am impressed by all that creativity. One surprise after another. great job.
We use cookies to ensure you get the best experience on our website. By browsing our site you agree to our use of cookies.
For more information check out our cookies policy.


text:
The Washington Post
June 22. 2014 7:37PM
Former vice president Dick Cheney sought Sunday to draw a sharp distinction between his position on Iraq and Sen. Rand Paul's, marking the latest fight over foreign policy in a Republican Party torn between military hawks and those who are far less keen on intervening abroad.
Appearing on a pair of Sunday morning news shows, Paul of Kentucky, argued that turmoil in the Middle East is at least partly the result of U.S. involvement in Iraq and Syria. Cheney, a leading advocate of military action in Iraq during the presidency of George W. Bush, hit back sharply against Paul's warnings about too much U.S. military action overseas.
"If we spend our time debating what happened 11 or 12 years ago, we're going to miss the threat that is growing and that we do face. Rand Paul, with all due respect, is basically an isolationist. He doesn't believe we ought to be involved in that part of the world. I think it's absolutely essential," Cheney said on ABC's "This Week with George Stephanopoulos."Paul said on CNN's "State of the Union" that "there's chaos in the Middle East, and I think the chaos is because we have created a vacuum. Before the Iraq war, I think there was somewhat of a standoff between Sunni and Shiite, had been for maybe 1,000 years off and on."He also said that the Islamic State of Iraq and Syria, a militant group fighting the Iraqi government, have been "emboldened" because "we have been arming their allies. We have been allied with ISIS in Syria. They have had a safe haven because we have been arming the rebels to keep [Syrian President Bashar al-Assad] away from them."
Cheney acknowledged that "there are no good, easy answers in Iraq." But he argued for a more robust U.S. military presence in the region.
"What I would do now," he said, "is, among other things, be realistic about the nature of the threat. When we're arguing over 300 advisers when the request had been for 20,000 in order to do the job right, I'm not sure we've really addressed the problem. I would definitely be helping the resistance up in Syria, in ISIS's back yard, with training and weapons and so forth, in order to be able to do a more effective job on that end of the party."
Paul said the United States needs to first see what the Shiites in Iraq will do to defend themselves against militants before it decides whether to launch airstrikes.
"If the Shiites aren't willing to fight for their country, it may be that their country is not going to exist," he said.
Democratic and Republican lawmakers weighing in Sunday agreed that ISIS is or could become a threat to U.S. national security.
"I believe it can be. I believe that they're recruiting in Europe," Senate Intelligence Committee Chairman Dianne Feinstein, D-Calif., said on "State of the Union."
Sen. Marco Rubio, R-Fla., said on CBS's "Face the Nation" that, "Without a doubt, I think this is an urgent counterterrorism matter. I know a lot has been talked about the future of Iraq itself as a country, and that's a very legitimate issue that needs to be looked at, but for me this is not about nation-building, or imposing democracy — this is a counterterrorism risk that we need to nip in the bud. It is my view that we will either deal with ISIS now or we will deal with them later. And later they are going to be stronger and harder to reach."


text:
Israeli Prime Minister Ehud Olmert heads to Washington this week for his final meeting with President George W. Bush, two lame-duck leaders looking to leave a blueprint for fulfilling their ambitious – but unrealized – Mideast agendas.
The three-day visit beginning Sunday will focus on Iran's nuclear program and progress in the Israeli-Palestinian peace talks launched by Bush last year.
Bush invited Olmert to a White House meeting as part of his final round of talks with world leaders before he leaves office on Jan. 20. Olmert, who announced his plans to resign in September amid corruption charges, will step down after a successor is chosen Feb. 10.
"It's a farewell, a double farewell," said Danny Ayalon, a former Israeli ambassador to Washington. "They will try to sum up a period and cement all the understandings and agreements between the U.S. and Israel over the last eight years."
Just a year ago, Olmert and Palestinian President Mahmoud Abbas proudly announced the resumption of peace talks after a seven-year hiatus at a summit hosted by Bush in Annapolis, Md. The three men set an ambitious target of wrapping up a final peace deal by the end of 2008.
Despite frequent negotiating sessions, two trips to the region by Bush and eight more by Secretary of State Condoleezza Rice, the sides have little to show for their efforts. They have acknowledged the year-end target won't be met.
With his time in power running out, Olmert has become increasingly candid, saying Israel will have to withdraw from almost all of the West Bank and parts of east Jerusalem to make peace with the Palestinians. Talk of such concessions was almost unheard of just a few years ago.
"I know that Mr. Olmert wants to leave to whomever is elected as the next prime minister the peace process in the best shape possible," said Olmert spokesman Mark Regev.
With hardline opposition leader Benjamin Netanyahu leading in polls, the future of peace talks appears especially murky. Netanyahu wants to keep much of the West Bank and all of east Jerusalem – areas captured by Israel in the 1967 Mideast war – and believes peace talks should be scaled down to discussions on the Palestinian economy. That approach has been rejected by the Palestinian leadership.
Even with time running out for both Olmert and Bush, it is not too late for them to take bold actions, such as drafting a peace deal with the Palestinians – or ordering an airstrike targeting Iran, said Avraham Diskin, a political science professor at the Hebrew University of Jerusalem.
In 1981, then-Prime Minister Menachem Begin ordered the bombing of an Iraqi nuclear reactor during an election campaign, and Ehud Barak offered the Palestinians a comprehensive peace deal as his own term came to a close in 2001, Diskin noted.
"There is super strong motivation for Olmert and for Bush to both leave their mark on history," he said.
Bush and Olmert will also tackle Iran's nuclear program, which Israel has identified as its biggest threat in light of Iran's development of long-range weapons and its president's repeated calls for the destruction of the Jewish state. A report this week by the U.N.'s International Atomic Energy Agency said Iran was stonewalling attempts to monitor its nuclear activities.
Israel believes Iran will be capable of building a bomb by 2010.
The U.N. Security Council has imposed three rounds of economic sanctions against Iran, which insists its nuclear program is peaceful and designed to produce energy. Both the U.S. and Israel say they hope diplomatic pressure resolves the standoff, but they have not ruled out military action.
Iran could be a point of contention between Israel and Bush's successor. President-elect Barack Obama has said he is willing to hold direct negotiations with Iran, a stance Israeli leaders have strongly opposed, saying it would reward the Tehran regime for extremism.
But in what may be a sign of things to come, Israel's military intelligence chief surprisingly softened the Israeli tone this week, saying he did not strictly oppose contact between the United States and Iran.
"Engagement is not appeasement," said Maj. Gen. Amos Yadlin.


text:
Real Salt Lake will be without their leading scorer in the second leg of the Western Conference Championship, but that's nothing new for the team this season.
Head coach Jason Kreis told reporters on a conference call on Friday that Álvaro Saborío will not make the trip to Portland for the second leg of his team's series with the Timbers on Sunday as they try to hang on to a two-goal aggregate lead and advance to MLS Cup (9 pm ET, ESPN, ESPN Deportes).
Saborío, who suffered a pulled muscle with 10 minutes remaining in RSL's 2-0 extratime victory over the LA Galaxy in the Conference Semifinals on Nov. 7, has been jogging around the field in practice this week, but still hasn't gotten on the field.
- Get more RSL news and notes at RealSaltLake.com
That's a familiar refrain for the team. Though Saborío leads Real Salt Lake in scoring this season with 12 goals, he has played in just 16 of 34 league games due to a combination of injuries and international duty.
And RSL, whose 57 regular-season goals was second only to New York's 58 in 2013, have spread the scoring around. Thirteen players put the ball in the net during the regular season, and two more joined them in the playoffs.
In the first leg of the series against the Timbers, rookie forward Devon Sandoval stepped in for Saborío and played one of his best games of the season. His goal in the 48th minute proved to be the game winner in Salt Lake's 4-2 win over Portland.
Saborío's season might not be over, however, if RSL can hang onto the two-goal lead. Kreis indicated that, with another two-week break before the MLS Cup final, the Costa Rican international could have time to get back into shape.


text:
Our other sites you have recently visited:
From desk to dusk stay smart with our range of tailoring. Opt for a stylish two piece or mix it up with mix & match - available in a wide range of colours and styles. From skirts, trousers, blazers and more we've got something for every body.
Refine your search…
clear all
You have chosen
New In
Sort By:
1 Item Found for Tailoring
Tie Sleeve Soft Jacket
Save from £12.50
was £40.00
from £23.00
More colours available
If you continue, we assume that you consent to receive all cookies on all our websites. You can find out more information about cookies here.


text:
Quick Search
Advanced Search
Custom Carrier
Shopping Cart
Sign In
Contact Us
Your Shopping Cart
There are currently no items in your shopping cart.
Our Products
Armor Accessories
BALCS Carriers
Interceptor OTV Carriers
Interceptor IOTV Carrier Improved Outer Tactical Vest
NIJ Carriers
Custom Body Armor Carrier
Chest Rigs
Chest Rig Accessories
Hydration Carriers
Plate Carriers
Plate Carrier Accessories
Combat Belts
Shotgun Scabbard
Short Barrel Scabbard
Tactical Hunting Gear
Tactical Load Mount Platform
Mag Shingles
Discounted Gear
Terms and Conditions
About Us
Site Map
Copyright © 2017. BeezCombatSystems.com. All rights reserved.


text:
Edit Article
wikiHow to Cook Mongolian Beef
Mongolian beef is a popular and deliciously authentic Chinese dish that makes a perfect side dish. Without ordering up a delivery or carry-out, you can serve the real deal, made at home. Your family and guests will be pleasantly surprised.
Makes 4 servings.
- 1 pound flank steak or sirloin (Mongolian beef)
- 1 egg white
- Pinch of salt
- 1 tsp sesame oil
- 1 tbsp cornstarch
- 4 green onions, chopped into 1 inch (2.5 cm) pieces diagonally
- 1 8-oz can baby corn
- 1 minced clove garlic
- 3 tbsp hoisin sauce
- 1 tbsp water
- 1 tbsp soy sauce, dark
- 1 tbsp Chinese rice wine or dry sherry
- 2 tsp rice vinegar
- 1/4 tsp chili paste
Everything Else:
- 1 tsp sugar
- 1 cup oil (for frying the beef)
- 2 tbsp oil (needed for stir-frying)
1Cut the Mongolian beef across the grain into bite-size or smaller) pieces.
2Combine the marinade ingredients in the medium mixing bowl. Make sure to add ingredients in the order they are listed.
3Add the meat pieces and coat well with the marinade. Then, let the meat marinate, undisturbed for thirty or forty minutes.
4Combine the sauce ingredients in a small mixing bowl. While the beef is marinating, add the ingredients, in the order listed, to a small mixing bowl. Stir each as it is add so that each ingredient is incorporated well. Set the sauce mixture aside.
5Prepare the green onions and garlic. As the meat continues to marinate, wash the green onions and pat dry with paper towels, then cut them on diagonal into 1 inch (2.5 cm) pieces. Strip the skin off your garlic and mince it.
6Rinse the baby corn in warm-to-hot water. Once sufficiently cleansed, drain, then pat dry with paper towels.
7Place 1 cup oil in a wok and heat. Once the oil comes to a temperature just below the smoke point, add the marinated beef and fry until it is cooked thoroughly. Drain the beef on paper towels and pour out the excess oil.
8Use a paper towel to clean the wok, then pour 2 tablespoons of fresh oil into the pan. Wait for the oil to come to temperature, then place the minced garlic into the pan. Stir-fry the garlic for a short time, then add the corn and onions into the pan and continue stir-frying.
9Form a well in the center of the wok. Lightly push the vegetables outwards. Pour in the sauce and bring to a slow boil, continually stirring with a wooden spoon until the mixture thickens.
10Add the sugar, and stir again. Then, bring the beef, vegetables, and sauce together.
Community Q&A
Ask a Question
200 characters leftSubmit
Things You'll Need
- Wok
- Medium and small mixing bowl
- Measuring spoons and measuring cups
- Wooden spoon
- Paper towels
Sources and Citations
- Original recipe found here
Made Recently
Did you try these steps?
Upload a picture for other readers to see.
Upload a picture for other readers to see.
Upload error
Awesome picture! Tell us more about it? Click here to share your story.
Article Info
Categories: Beef and Lamb
Thanks to all authors for creating a page that has been read 3,492 times.
Did this article help you?


text:
SEMLIN (Hung. Zimony ; Servian, Semun), a town of Austria-Hungary, the easternmost in the Military Frontier district, stands on the south bank of the Danube, on a tongue of land between that river and the Save. It is the. see of a Greek archbishop, has a real school of lower gmde, five Roman Catholic and two Greek churches, a synagogue, a theatre, and a custom-house. The population (10,046) consists mostly of Servians, with a few Germans, Greeks, Illyrians, Croats, Gipsies, and Jews. Semlin has recently undergone improvement in its streets and build-ings ; but its suburb Franzenthal near the Danube consists mostly of mud huts thatched with reeds. The town is surrounded by a stockade. On the top of Zigeunerberg are the remains of the castle of John Hunyadi, who died here in 1456. Semlin has a considerable trade, sending woollen cloth, porcelain, and glass to Turkey, and obtain-ing in return yarn, leather, skins, honey, and meerschaum pipes. It is a principal quarantine station for travellers from Turkey. Steam ferry boats cross to Belgrade several times a day, and larger vessels run up the Save as far as to Sissek.
Citing this material
Please include a link to this page if you have found this material useful for research or writing a related article. Content on this website is from high-quality, licensed material originally published in print form. You can always be sure you're reading unbiased, factual, and accurate information.
Highlight the text below, right-click, and select "copy". Paste the link into your website, email, or any other HTML document.


text:
The Brewery
Hermit Thrush Brewery is the brainchild of President and Brewmaster Christophe Gagné and his beer-loving friend and Vice President Avery Schwenk. Together, Christophe and Avery are dedicated to providing top quality Belgian inspired ales to the residents and visitors of Brattleboro, Vermont. Through the use of historical brewing processes, oak casks, and new green technologies, we make exciting, yet accessible, beer while keeping an eye on minimizing our environmental impact.
The Brewers
Christophe and Avery met over a decade ago as students at Swarthmore College in Pennsylvania where they cohosted a radio show featuring their rather eclectic music tastes. After school, they parted ways, but remained close friends. Christophe, a native of upstate New York, remained in the Philadelphia area and acquired the skills and tools of a master brewer, sous chef, cheesemonger and social worker. Avery, born and raised in southeast Minnesota, sated his wanderlust and thirst for excitement with a stint in Canada and training as a paramedic, meanwhile developing a taste for fine beer and food. After Avery relocated back to Philadelphia, they hatched a plan together to open a fine microbrewery and to migrate from the city to a place that fed their desire for community, nature and environmental awareness. Thus, Hermit Thrush Brewery was formed! With Christophe's talent for brewing and industriousness and Avery's persistence and esoteric knowledge, the two have embarked on an adventure that culminates, as all good adventures should, in world-class beer.
Christophe Gagné, President and Brewmaster
Christophe has been brewing for about 6 years, and has worked in or completed apprenticeships in three breweries. During Philadelphia's 2011 and 2012 Beer Week festivals, Chris brewed two batches on Philadelphia brewpub Nodding Head's system as a featured guest. In 2011, he produced a Tart Cherry Lambic fermented with his own strain of lambic yeast and aged in bourbon barrels. In 2012, he brewed a Farmhouse Amber Ale aged in barrels inoculated with three of his yeast strains. He has continued to refine his Belgian beers and now maintains quite an impressive library of international and wild yeasts he collected over the years.
Avery Schwenk, Vice President and Brewer
Avery has been a craft beer enthusiast for over a decade. He was most recently employed as a Paramedic in the Philadelphia metropolitan area. He has always had a passion for teaching and mentoring, even during his schooling in physics and music. For the past 12 years, Avery spent hundreds of volunteer hours annually in leadership, management and consultant roles for Destination Imagination, the international creative problem-solving organization. Along with his diverse experience and background, Avery is a specialist in lateral thinking, critical decision making, on-the-fly problem-solving, personnel training and hands-on management. He also really likes flying kites when the wind is right.


text:
This product is no longer available.
You can try these similar gifts instead.
Classic Fuchsia Glass Water Bottle
Takeya USA
Help our planet by reducing all the plastic water bottles in land fields. This water bottle is made of glass and comes with a silicone protective cover. The glass also means no more plastic or metal taste. 16 ozs.