text:
Protective effects of aerobic exercise on acute lung injury induced by LPS in mice
- Cintia Tokio Reis Gonçalves1,
- Carlos Gustavo Reis Gonçalves1,
- Francine Maria de Almeida2,
- Fernanda Degobi Tenório Quirino dos Santos Lopes2,
- Ana Carolina Cardoso dos Santos Durão4,
- Fabiana Almeida dos Santos4,
- Luiz Fernando Ferraz da Silva1,
- Tania Marcourakis4,
- Hugo C Castro-Faria-Neto3,
- Rodolfo de Paula Vieira1, 5 and
- Marisa Dolhnikoff1Email author
DOI: 10.1186/cc11807
© Gonçalves et al.; licensee BioMed Central Ltd. 2012
Received: 12 June 2012
Accepted: 18 September 2012
Published: 18 October 2012
The regular practice of physical exercise has been associated with beneficial effects on various pulmonary conditions. We investigated the mechanisms involved in the protective effect of exercise in a model of lipopolysaccharide (LPS)-induced acute lung injury (ALI).
Mice were divided into four groups: Control (CTR), Exercise (Exe), LPS, and Exercise + LPS (Exe + LPS). Exercised mice were trained using low intensity daily exercise for five weeks. LPS and Exe + LPS mice received 200 µg of LPS intratracheally 48 hours after the last physical test. We measured exhaled nitric oxide (eNO); respiratory mechanics; neutrophil density in lung tissue; protein leakage; bronchoalveolar lavage fluid (BALF) cell counts; cytokine levels in BALF, plasma and lung tissue; antioxidant activity in lung tissue; and tissue expression of glucocorticoid receptors (Gre).
LPS instillation resulted in increased eNO, neutrophils in BALF and tissue, pulmonary resistance and elastance, protein leakage, TNF-alpha in lung tissue, plasma levels of IL-6 and IL-10, and IL-1beta, IL-6 and KC levels in BALF compared to CTR (P ≤0.02). Aerobic exercise resulted in decreases in eNO levels, neutrophil density and TNF-alpha expression in lung tissue, pulmonary resistance and elastance, and increased the levels of IL-6, IL-10, superoxide dismutase (SOD-2) and Gre in lung tissue and IL-1beta in BALF compared to the LPS group (P ≤0.04).
Aerobic exercise plays important roles in protecting the lungs from the inflammatory effects of LPS-induced ALI. The effects of exercise are mainly mediated by the expression of anti-inflammatory cytokines and antioxidants, suggesting that exercise can modulate the inflammatory-anti-inflammatory and the oxidative-antioxidative balance in the early phase of ALI.
Acute lung injury (ALI) and its most severe presentation, acute respiratory distress syndrome (ARDS), are clinical disorders characterized by hypoxemic respiratory failure associated with acute pulmonary inflammation secondary to several different etiologies and exhibit high mortality rates [1].
The regular practice of exercise has been increasingly associated with beneficial effects on chronic pulmonary conditions such as asthma and chronic obstructive pulmonary disease [2, 3]. However, few studies have investigated the effects of aerobic exercise on acute lung injury (ALI). In 2008, Mussi et al. demonstrated the beneficial effects of exercise in a rat model of pulmonary inflammation induced by lung ischemia-reperfusion [4]. Some effects of exercise have been reported also in lipopolysaccharide (LPS) models of ALI. Cannon and Kluger showed in 1984 that mice trained on running wheels and then injected with Salmonella typhimurium had a significantly higher survival rate than sedentary mice [5]. More recently, Ramos et al. showed that exercise reduced neutrophilic inflammation and exhaled NO levels in mice submitted to intra-nasal instillation of LPS [6]. LPS is one of the major proinflammatory constituents of the cell walls of gram-negative bacteria and has been largely used in animal models of acute lung inflammation where neutrophils, acute phase cytokines and reactive oxygen species play major roles [7].
In this study, we investigated the mechanisms involved in the protective effect of exercise in a model of LPS-induced ALI. For this purpose, we analyzed lung mechanics, lung tissue inflammation, protein leakage, pulmonary and systemic cytokine levels, the expression of glucocorticoid receptor (Gre) in lung tissue and pulmonary antioxidant enzyme activity in mice instilled with LPS after five weeks of daily aerobic exercise.
Materials and methods
This study was approved by the review board for human and animal studies of the School of Medicine at the University of São Paulo (São Paulo, Brazil), protocol 0402/08. All animals in the study received humane care in compliance with the Guide for the Care and Use of Laboratory Animals (NIH publication 85-23, revised 1985).
Animals and experimental design
Thirty-two male BALB/c mice (20g to 25 g) were divided into four groups (n = 8 in each group): Control (non-exercised and non-LPS-instilled), Exercise (Exe; exercised and non-LPS-instilled), LPS (non-exercised and LPS-instilled), Exe + LPS (exercised and LPS-instilled).
Aerobic exercise treadmill test and exercise conditioning
Additional file 3: Video of treadmill with mice. The video illustrates the mice during exercise. (MPEG 8 MB)
LPS instillation
Forty-eight hours after the last exercise capacity test, animals from the LPS and Exe + LPS groups received one intratracheal instillation of 200 µg of Escherichia coli LPS (L3755, Sigma Aldrich, St. Louis, MO, USA) suspended in saline solution (total volume = 0.05 ml per animal). Animals from the Control and Exe groups received one intratracheal instillation of 0.05 ml saline solution. For intratracheal instillation, the mice were anesthetized with ketamine (0.04 ml/mice) and xylasine (0.1 ml/mice); then, a 1 cm-long midline cervical incision was made to expose the trachea, and LPS or saline was instilled using a bent 27-gauge tuberculin needle. The cervical incision was closed with a 5.0 silk suture, and the mice were returned to their cages. The animals recovered rapidly after surgery [8].
Measurement of the exhaled nitric oxide (eNO) concentration
Twenty-four hours after the intratracheal instillation with saline or LPS, the animals were anesthetized using pentobarbital sodium (50 mg/kg i.p.), tracheostomized, and mechanically ventilated at 60 breaths/min with a tidal volume of 10 ml/kg using a Harvard 683 ventilator (Harvard Apparatus, South Natick, MA, USA). eNO levels were measured at the expiratory port of the ventilator using a Mylar bag (3 to 6) for five minutes. The concentrations of eNO were measured by chemiluminescence using a fast-responding analyzer (NOA 280; Sievers Instruments Inc., Boulder, CO, USA). Before each measurement, the analyzer was calibrated with a certified 47-ppb NO source (White Martins, São Paulo, Brazil) and a zero NO filter (Sievers Instruments Inc.). To avoid environmental contamination, an NO filter was attached to the breathing circuit [9].
Respiratory system mechanics
The tracheal pressure (Ptr) was measured using a pressure transducer (DP 45-28-2114, Validyne, Northridge, CA, USA) connected to a side tap in the orotracheal cannula. Airflow (V. ) was measured using a pneumotachograph (Fleisch-4.0, OEM Medical, Richmond, VA, USA) attached to the tracheal cannula and to a differential pressure transducer (Validyne DP 45-16-2114). Ptr and V. signs were registered using a Gould RS-3400 recorder (Gould Instruments, Cleveland, OH, USA), sampled at 200 Hz using an analog-to-digital converter (DT 2801 A, Data Translation, Marlboro, MA, USA), and stored in a microcomputer. Lung volume (V) changes were obtained by electronic integration of V. . The respiratory system resistance (Rrs) and elastance (Ers) were computed by least squares fitting of the measured values of Ptr, V, and V. over 9 to 10 respiratory cycles using the following equation of motion of the respiratory system:
Ptr (t) = Ers × V(t) + Rrs × V. (t), where t is time. All data were collected and processed using LABDAT software (RHT-InfoData, Montreal, Quebec, Canada) [10].
Total and differential cell counts in bronchoalveolar lavage fluid (BALF)
After the mechanical parameters were measured, the mice were euthanized by exsanguination (blood collection through the abdominal vein), and BALF was collected by flushing the lungs three times with 0.5 ml of 37°C sterile, pyrogen-free, physiological saline (0.9% NaCl) via the tracheal cannula. After BALF collection, the samples were centrifuged at 420 × g at 4°C for 15 minutes, and the supernatant was stored at -70°C for subsequent analysis of protein and cytokine levels. The cell pellets were resuspended in 1 ml of PBS, and the total cell counts were performed using a Neubauer chamber. For differential cells counts, cytospin slides were prepared and stained with Diff-Quick; 300 cells were counted per slide [3, 11].
Evaluation of cytokines in BALF
Levels of IL-1β, IL-6, KC (the murine functional homolog to IL-8), IL-10 and TNF-α in the cell-free BALF were evaluated using ELISA in accordance with the manufacturer's instructions (Duo Set, R&D Systems, Minneapolis, MN, US) [12].
Protein leakage in BALF
Proteins from lung lavage supernatant were quantified using the bicinchoninic acid (BCA) method to evaluate lung vascular permeability [11].
Evaluation of plasma cytokines
Blood was collected through the abdominal vein for the measurement of cytokines. The blood was put on ice, and plasma was collected by centrifugation at 800 × g for 15 minutes at 4°C, aliquoted and stored at -70°C until analyzed. Levels of IL-6 and IL-10 were evaluated using ELISA in accordance with the manufacturer's instructions (Duo Set, R&D Systems, Minneapolis, MN, USA) [12].
Lung morphometry
Lung tissue was fixed in buffered 10% formaldehyde for 24 hours, routinely processed and embedded in paraffin. Five-µm-thick slides were stained with H & E for analysis of the polymorphonuclear (PMN) cell content [13]. The expression of IL-6, IL-10, TNF-α, SOD-2, and glucocorticoid receptor was assessed with immunohistochemistry as previously described [3]. Briefly, sections were deparaffinized and 0.3% hydrogen peroxide was applied for 35 minutes to inhibit endogenous peroxidase activity. Antigen retrieval was performed using citrate solution for 45 minutes to inhibit endogenous peroxidase activity. The sections were incubated overnight at 4°C with anti-IL-6 (1:200) (R&D Systems, Minneapolis, MN, USA), anti-IL10 (1:900), anti-TNF-α (1:400), anti-SOD-2 (1:400) and anti-Gre (1:500) (Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA). An ABC Vectstain Kit (Vector Elite PK-6105, Vector Laboratories, CA, USA) was used as the secondary antibody, and 3,3 diaminobenzidine (Sigma) was used as the chromogen. The sections were counterstained with Harris hematoxylin (Merck, Darmstadt, Germany).
Using conventional morphometry, we assessed the density of PMN cells and cells that were positive for IL-6, IL-10, TNF-α, SOD-2 and Gre within the alveolar parenchyma. Using a 100-point grid of known area (62,500 µm2 at × 400 magnification) attached to the ocular of the microscope, we counted the number of points hitting alveolar tissue and the number of PMN and positive cells in each field. The cell density was determined as the number of positive cells in each field divided by the tissue area and expressed as cells/mm2 [13]. The morphometric measurements were performed on 15 fields for each animal at x400 magnification by an investigator blinded to the group studied.
Antioxidant enzyme activity assays
The enzymatic activity of catalase (CAT) was determined in lung homogenates using spectrophotometry. Catalase activity was evaluated by measuring the consumption of hydrogen peroxide according to Aebi [14]. The decrease in absorbance was monitored spectrophotometrically (Biochrom Libra S12) at 25°C and 240 nm for 60 seconds.
Glutathione peroxidase (GPX) activity was determined using tert-butylhydroperoxide as substrate, and the formation of oxidized glutathione (GSSG) was indirectly monitored spectrophotometrically through NADPH consumption detected for five minutes at 340 nm [15].
Glutathione reductase (GR) activity was determined based on the method of Carlberg and Mannervik [16]. The reduction of GSSG to GSH was measured through NADPH consumption, which was monitored spectrophotometrically at 37°C and 340 nm for five minutes.
Glutathione S-transferase (GST) activity was determined by measuring the conjugation of 1-chloro-2,4- dinitrobenzene (CDNB) with reduced glutathione based on the method of Habig et al. [17]. The formation of the complex was monitored spectrophotometrically at 25°C and 340 nm for five minutes. The GPX, GR and GST assays were performed using a Power Wave × 340 spectrophotometer (Bio-Tek Instruments Inc., software KC4 v3.0).
Malondialdehyde (MDA)
MDA was quantified in homogenates of lung tissue precipitated with 7.2% trichloroacetic acid solution, centrifuged, and incubated with thiobarbituric acid (TBA) at 0.6% (Sigma) for 45 minutes at 90°C [18]. Then, the supernatant was cooled for five minutes, and n-butanol was added to extract the color product of the aqueous solution. After centrifugation, the MDA in the butanol layer was measured at 532 nm. HPLC analysis was performed using a LC-VP HPLC system from Shimadzu (Kyoto, Japan). The concentration of total protein in each sample of homogenate was determined using the Bradford Method and BSA as a standard (1 mg/ml). MDA was expressed in nanomoles per milligram of total protein.
Statistical analysis
Statistical analysis was performed using the SPSS 15.0® software package (SPSS, Chicago, Illinois, USA). The normality of the data was tested using the Kolmogorov-Smirnov test. Logarithmic data transformation was applied when the data followed a nonparametric distribution. Pulmonary resistance was the only parameter that showed a parametric distribution after logarithmic transformation. A two-way analysis of variance was performed to resolve the main effects of LPS and exercise on the parameters analyzed. This test also produces an interaction term that identifies whether the effects of one factor (LPS) are influenced by the effects of the other (exercise). The associations among the various parameters in LPS-instilled animals were evaluated using Pearson or Spearman tests, depending on data distribution. The results are expressed as the mean ± standard deviation or median (interquartile range). The level of significance was set at P <0.05.
Aerobic exercise treadmill test and exercise conditioning
Non-trained animals showed a significant decrease in maximal exercise capacity between the first and second tests (test 1 = 1.5 km/hour, test 2 = 1.3 km/hour, P= 0.001). Trained animals showed no difference in maximal exercise capacity between the first and second tests (test 1 = 1.6 km/hour, test 2 = 1.6 km/hour).
Respiratory mechanics
Concentration of exhaled NO
Protein leakage in BALF
We observed an effect of LPS in increasing the protein concentration in BALF (P <0.001) but exercise did not attenuate this effect. CTR = 1.88 (0.59) µg/ml, Exe = 1.73 (0.43) µg/ml, LPS = 3.86 (1.99) µg/ml, and Exe + LPS = 3.41 (2.47) µg/ml.
Cell counts in BALF
Total and differential cell counts in bronchoalveolar lavage fluid (cells/ml).
total cells
1.35 ± 1.71
1.30 ± 2.01
8.73 ± 3.08a
7.30 ± 0.68
0.04 ± 0.04
0.04 ± 0.05
7.28 ± 1.56a
6.00 ± 3.02
0.04 ± 0.07
0.02 ± 0.02
0.15 ± 0.14
0.16 ± 0.20
1.11 ± 0.50
1.00 ± 0.60
1.12 ± 0.60
0.86 ± 0.60
0.02 ± 0.04
0.01 ± 0.03
0.04 ± 0.05
Plasma and BALF cytokine levels
Cytokine levels in plasma and BALF (ng/ml).
0.015 ± 0.002
0.011 ± 0.005
0.541 ± 0.445a
0.767 ± 0.664
IL-6 plasma
0.016 ± 0.008
0.011 ± 0.003
0.096 ± 0.029a
0.059 ± 0.037
0.009 ± 0.032
0.050 ± 0.048
0.066 ± 0.072
0.056 ± 0.041
IL-10 plasma
0.013 ± 0.034
0.058 ± 0.278
0.351 ± 0.176a
0.111 ± 0.215
IL-1β BALF
0.150 ± 0.033
0.106 ± 0.060
0.161 ± 0.186a
0.357 ± 0.246b
0.017 ± 0.011
0.013 ± 0.007
0.596 ± 0.233a
0.626 ± 0.121
TNF-α BALF
0.018 ± 0.016
0.028 ± 0.018
0.027 ± 0.017
0.032 ± 0.029
PMN cell content in lung tissue
Cytokine expression in lung tissue
Antioxidant enzyme activity and MDA levels in lung tissue
SOD-2 expression in lung tissue
Glucocorticoid receptor expression in lung tissue
Significant correlations between cytokine levels, inflammatory cell counts, exhaled NO, and mechanical parameters in the LPS and exercise + LPS groups.
Neutro T
Neutro B
IL-1β B
Exhaled NO
Neutro T
TNF-α T
This study investigated the mechanisms involved in the protective effects of aerobic exercise in a model of ALI induced by LPS. LPS instillation resulted in increased levels of eNO, higher numbers of total cells and neutrophils in BALF, higher number of neutrophils and TNF-α positive cells in the lung parenchyma, higher values of pulmonary resistance and elastance, increased protein leakage, increases of IL-6 and IL-10 levels in plasma, increases of IL-1β, IL-6 and KC levels in BALF, and higher activities of GPX and GR in lung tissue. We demonstrated that the low intensity exercise performed during the five weeks before intratracheal instillation of LPS decreased pulmonary resistance and elastance, inhibited neutrophilic tissue infiltration and the expression of TNF-α in lung tissue, decreased the concentration of eNO, increased the expression of SOD-2, glucocorticoid receptors, IL-6 and IL-10 in lung tissue and the levels of IL-1β in BALF. These results suggest that aerobic exercise may play an important role in protecting the lung from the inflammatory effects of LPS-induced ALI by altering the inflammatory profile and increasing the expression of anti-oxidants in lung tissue.
Few studies to date have investigated the effects of aerobic preconditioning on the inflammatory changes involved in acute lung injury. MUSSI et al. evaluated the benefits of exercise in a rat model of pulmonary inflammation induced by lung ischemia-reperfusion and observed decreases in protein leakage and plasma levels of IL-1β and TNF-α and an increase in SOD activity in trained animals [4]. In the present study, we used intratracheal instillation of LPS as a model of ALI induced by gram-negative bacteria. The main difference between the study of MUSSI et al. and ours was the marked effect of exercise on decreasing LPS-induced pulmonary inflammation as assessed by neutrophilic infiltration and eNO.
We observed an effect of both LPS and exercise on the release of IL-6. IL-6 is one of the first acute phase cytokines released in sepsis/endotoxemia and is followed by increases in the levels of IL-1β, IL-8, TNF-α and IL-10 [2]. Consistently, there was an increase in IL-6 levels in both plasma and BALF of LPS-instilled animals in our model. Whether the increasing of pulmonary and plasmatic IL-6 in ALI is detrimental or protective is controversial. IL-6 was previously considered exclusively as a pro-inflammatory cytokine, and the circulating levels of IL-6 were directly correlated with the severity of ALI [19]. Currently, the anti-inflammatory effects of IL-6 have been demonstrated [20–24]. Evidence for the protective anti-inflammatory effects of IL-6 is derived from studies that show that endogenous IL-6 in endotoxin-induced ALI controls the level of pro-inflammatory cytokines and neutrophilic inflammation [24]; also, the administration of IL-6 induces SOD production and reduces LPS-induced neutrophilic infiltration in liver in a model of endotoxemia in rats [21]. Further, it has been reported that IL-6 plays a protective role in limiting the disruption of the alveolar barrier by neutrophils [23].
An exercise-induced increase in IL-6 expression in lung tissue was observed in our trained animals of both the Exe and LPS + Exe groups. Evidence regarding the effects of exercise on the release of IL-6 is accumulating [2, 25, 26]. An increase in circulating levels of IL-6 is consistently found during aerobic exercise; however, a decline in the levels of IL-6 has been observed during the post-exercise period [2, 25]. The dynamics of the plasma variation of IL-6 levels induced by exercise could explain the low levels of plasmatic IL-6 observed in our Exe group because this analysis was performed 72 hours after the last training session.
IL-6 has been shown to stimulate the production of IL-10, a cytokine with well known anti-inflammatory effects [2, 21, 27, 28]. Interestingly, in our animals the higher tissue expression of IL-6 was associated with the higher expression of IL-10 in lung tissue; we further observed a negative association between these two anti-inflammatory cytokines and the density of neutrophils in lung tissue.
Distinct mechanisms have been proposed for the anti-inflammatory effects of IL-6 in acute or chronic conditions [24]. In acute inflammatory responses, as those elicited by LPS, IL-6 operates to control the extent of tissue inflammatory responses by inhibition of pro-inflammatory cytokines and induction of anti-inflammatory molecules. When chronically released, as when induced by repeated bouts of exercise, IL-6 could induce the beneficial anti-inflammatory effects by modulation of the immune system, as suggested in previous studies that showed that IL-6 treatment may modulate the hypothalamic-pituitary-adrenal (HPA) axis and autoregulate serum IL-6 levels in response to LPS [21, 26, 29]. Furthermore, prolonged administration of IL-6 in humans led to adrenal enlargement and identification of IL-6 receptors in the adrenal cortex in mice led to the suggestion that the direct stimulatory effects of IL-6 mediate glucocorticoid release [29]. Increased glucocorticoid secretion leads to the restraining of the further production of pro-inflammatory mediators [29, 30], thus preventing propagation of the stress response [29]. We believe that exercise could have induced the release of small doses of IL-6 after each training period in our animals, and this would chronically modulate the HPA axis to stimulate the constant release of glucocorticoids [26, 29]. Although we did not measure the serum levels of glucocorticoids, the increase in the expression of glucocorticoid receptors in pulmonary inflammatory cells in the trained animals suggests that modulation of the HPA axis could be one of the anti-inflammatory effects induced by exercise in our model. Taken together, our findings suggest that pulmonary release of IL-6 and IL-10 is a major mechanism involved in the protective effect of exercise in this LPS-induced ALI model.
We observed an interaction effect of LPS and exercise in increasing the levels of IL-1β in BALF, indicating that exercise exacerbates the effect of LPS in increasing IL-1β levels. IL-1β is involved in the repair of the alveolar epithelium in the early phase of ARDS through activation of the epithelial epidermal growth factor/transforming growth factor α pathway [31–33]. One of the most important factors that determine the severity of lung injury in ARDS is the magnitude of injury to the alveolar epithelial barrier. The possibility of decreasing the inflammatory process at an early stage or accelerating tissue repair can be a major determinant of recovery [31]. Although the process of alveolar epithelial repair involves several growth factors, cytokines and various extracellular matrix components, it is possible that a further protective effect of exercise on ALI is to promote early tissue repair through IL1-β release.
Levels of TNF-α were not elevated in BALF after LPS instillation but increased expression of TNF-α in lung tissue was observed in LPS-treated animals. Aerobic exercise resulted in a significant effect on decreasing LPS-induced TNF-α expression. Moreover, values of TNF-α in lung tissue were correlated with the density of neutrophils. TNF-α is a major mediator of sepsis and endotoxin-induced ALI; after endotoxin infusion in animals, the level of TNF-α peaks in one to two hours in the serum and in eight hours in BALF. However, due to its short half-life, TNF-α is rapidly cleared and returns to baseline levels within a few hours [34, 35]. We believe that this dynamic of the release and clearance of TNF-α could explain the observed low levels of this cytokine in the BALF of our animals, which was collected 24 hours after LPS instillation. We also observed a striking decrease of eNO in our exercised animals. Elevated NO levels are thought to play a central role in tissue damage observed during septic shock [21]. Previous results suggest that NO release after LPS challenge is mediated through IFN-γ and TNF-α [36]. Based on previous observations that pretreatment with IL-6 decreased the levels of TNF-α, NO and other pro-inflammatory cytokines in a model of endotoxemia in mice [21], we suggest that in our model, the low levels of eNO and TNF-α in the exercised animals could, at least in part, be secondary to the continuous release of IL-6 induced by exercise. The negative correlation between the levels of TNF-α and IL-6 in lung tissue in our animals is compatible with this hypothesis.
The aerobic exercise did not alter the effects of LPS on KC release and protein leakage in BALF. These findings were unexpected because KC is a major neutrophil chemotactic factor, and exercise induced a significant reduction in neutrophil density. KC levels were not measured in plasma or pulmonary tissue, limiting the interpretation of our results.
We observed an effect of exercise on decreasing pulmonary resistance and elastance in LPS-instilled animals. Alteration of resistive forces and tissue viscoelastic properties is a major characteristic of ALI and is associated with alveolar barrier disruption, alveolar edema, surfactant dysfunction, collapse and alveolar inflammation [8]. In our animals, there was no significant effect of exercise on protein leakage, and the decrease of pulmonary resistance and elastance in LPS-instilled exercised mice is likely related to the decrease in pulmonary inflammation. The significant correlation between the levels of eNO and values of resistance and elastance is consistent with this mechanism.
To investigate the role of oxidative stress, we analyzed the enzymatic activities of GST, CAT, GPX, and GR, the levels of MDA and the expression of SOD-2 in lung tissue. The levels of MDA, which were used as an index of oxidative stress, were not different between the LPS group and controls. Previous studies have shown that the levels of MDA peak four to five hours after LPS instillation [37, 38]. Changes in MDA levels can be undetectable after 8 or 24 hours [38], as observed in our animals. Moreover, we observed that LPS instillation induced activation of the antioxidant glutathione pathway by increasing the activities of GPX and GR, indicating a possible physiologic response to an oxidative stress [39]. Exercise determined an increase in the expression of SOD-2 in lung tissue. SOD-2 is exclusively localized to the mitochondria, a critical cell organelle both in cellular energy metabolism and cell survival [40]. Overall, SOD-2 is most highly expressed in alveolar type II epithelial cells and alveolar macrophages, cell types with relatively high metabolic capacity, and plays a major role in protecting lung tissue against free radicals [40].
In conclusion, our results show that aerobic exercise plays an important role in protecting the lung from the inflammatory effects of LPS-induced ALI. The effects of exercise are mainly mediated by the increased expression of anti-inflammatory cytokines and antioxidants, suggesting that aerobic exercise can modulate the inflammatory-anti-inflammatory and the oxidative-antioxidative balance in the early phase of ARDS.
Key Messages
Aerobic exercise performed during five weeks prior to LPS instillation attenuates the pulmonary changes induced by LPS.
The beneficial effects of exercise in this ALI model are mainly mediated by the anti-inflammatory cytokines IL-6 and IL-10 and by the expression of SOD-2.
Our data suggest that exercise can modulate the inflammatory-anti-inflammatory and the oxidative-antioxidative balance in the early phase of ALI.
acute lung injury
acute respiratory distress syndrome
bronchoalveolar lavage fluid
bovine serum albumin
enzyme-linked immunosorbent assay
- eNO:
exhaled nitric oxide
- Ers:
respiratory elastance
- Exe:
glutathione peroxidase
glutathione reductase
- Gre:
glucocorticoid receptors
oxidized glutathione
glutathione S-transferase
hematoxylin and eosin
high performance liquid chromatography
Escherichia coli lipopolysaccharide
phosphate-buffered saline
- Ptr:
tracheal pressure
- Rrs:
respiratory system resistance
superoxide dismutase
Statistical Package for the Social Sciences
tumor necrosis factor
lung volume.
CTRG receives a fellowship from Coordenação de Aperfeiçoamento Pessoal de Nível Superior (CAPES). MD receives an individual research grant from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). The study was supported by the Laboratórios de Investigação Médica-LIMs 05 e 20 do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (LIMHC-FMUSP).
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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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25 August 2016
02 August 2016
Some wall painting for Seen Display at the Tea Buildings. No faffing quick sketches then getting to it.
04 May 2016
I enjoyed doing a few days of live painting at the VM & Display show at the Business Design Centre in London a few weeks ago. Thanks to everyone who came and paid me a visit on my doodling days.
07 April 2016
I did a load of editorial illustrations for the Mail Online about an anonymous couple of first time buyers trying to navigate the minefield of dodgy estate agents, overpriced and dramatically damp flats, and tricks of the trade in their pursuit for a home. Read some of the articles here, here, here and with a bit of a happy ending - here.
08 October 2015
Celebrating light in darkness and the triumph of good, this festival of light is one of the most magical, colourful and welcoming. The above is my first and second poster drafts for the celebrations at the community gardens in East Ham, a beautiful and inclusive place full of hard working chutney making, pumpkin baking staff and volunteers, a perfect venue to celebrate Diwali.
28 August 2015
One of my absolute favourite projects so far this year was being commissioned by The Spark to create an instillation depicting their specially commissioned poem celebrating the 75th anniversary of Southfields Library (now re-opened and re-vamped and re-named 'Pork Pie Library and Community Centre' ) It was great to approach them with a design and be given the freedom to go ahead and create it from scratch. It's a permanent piece so you can sit back down and have one more cup of tea before rushing over there in hoards.
20 July 2015
16 July 2015
Beautiful sign engraved on plastic by The Manchester Rubber Stamp Company. I'll post some pictures of the project I had it made for next!
03 July 2015
Eid al-Fitr, which is on the first day of the Islamic month of Shawwal, marks the end of the month-long fast of Ramadan, obviously! If you are in East London why not celebrate at Bonny Downs Community Garden in East Ham. I made them the above poster as part of their year of interfaith festivities.
05 June 2015
I did an advert illustration and an editorial doodle for some business mags! Art Direction Hidden Gem Design.
27 May 2015
A few months ago I exhibited at Lauderdale House in London with Arachne Press. The paintings I made for the show were all based on my recent visit to Rome. The characters in the fountains, the ruins, the beasties. Above are a few of the paintings. Most are available to purchase so if you would like a piece of original art then get in touch.
20 May 2015
Caroline and her team at Holmqvist Design have a new website! Have a look here! I did the little doodley icons for it.
24 April 2015
I did the lettering for the 2015 revised edition of the Scout's handbook 'Prepared' See more of the images on my website. The book can be bought here. Art direction and book design by Jo Bateman.
19 March 2015
18 March 2015
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- Photos
- Map/Street View
- Things Nearby
The Villages at Marley Station in Glen Burnie, MD is where you'll find beautiful, convenient and affordable studios, one-, two- and three-bedroom apartment homes. Here you can enjoy many amenities, including a swimming pool, fitness center, basketball court, play areas, and → Read More
| The Villages at Marley Station in Glen Burnie
MD is where you'll find beautiful
convenient and affordable studios
| two- and
three-bedroom apartment homes. Here you can enjoy many
including a swimming pool
fitness center
basketball court
| play areas
and community center. In addition
we offer an after-school and summer programs for kids
and a computer room. We're easily accessible to Routes 2
| 100
and 295. Public transportation is available on-site and we are on local Bus #14. We're a short drive to Marley Station Shopping Center
| Arundel Mills
Fort Meade
Annapolis Mall and BWI Marshall Airport. Please note we are a moderate-affordable community with income minimums
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TCL 50" S4800FS Full HD LED LCD Smart TV50S4800FS 9335024003494
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Get more out of your TV without the big brand price tag with the TCL 50" S4800 Full HD LED LCD Smart TV. Now with Netflix* compatibility and a range of handy features and options, this TCL TV is a great addition to any living room.
The Connected Life
True to Life Pictures
Watching movies at home will never be the same with the TCL 50" Full HD LED LCD Smart TV. A brilliant full HD 1920x1080 resolution makes images crisp and lifelike. Featuring 16.7 million colours, you're guaranteed to capture every detail when watching your favourite TV show or film.
State-of-the-Art Technology
Enjoy streaming online content on this TCL smart TV with built-in WiFi. Check your social media messages and newsfeed and keep yourself abreast with breaking news from your favourite news media outlets. Watch free-to-air TV channels worldwide in the comfort of your own lounge room TCL GoLive 2.0.
Brilliant Audio
Equipped with Dolby Digital Sound capabilities, you and your family are treated to stellar audio whenever you watch a movie or stream online content on this TCL smart TV. Hear every shudder, whisper, and minute audio effect with brilliant clarity for that exceptional HD audio experience.
Record Your Favourite Shows
Don't miss your favourite shows with this TCL TV's USB PVR. The personal video recorder (PVR) feature allows you to record live free-to-air TV to a compatible external USB stick. Record shows and movies even when you're away and watch it later or anytime you'd like to see it.
Image quality of upscaled content will vary based on the source resolution.
*Internet connection required to use Smart TV features. Subscription services (such as Netflix) will incur monthly subscription fees if you choose to subscribe.
**Data charges may apply. Please consult your internet service provider for more information about data allowances and costs on your home network.
|Barcode (GTIN)
|LED LCD TVs
|TV Type
|Smart TVs
|Screen Type
|Screen Size (inches)
|Screen Definition
|Full High Definition
|Screen Resolution
|1920 x 1080
|No. HDMI Ports
|Digital Audio Out, USB 2.0, VGA, Wi-Fi
|Digital Audio Out, VGA, Wi-Fi, USB 2.0
|Built-In Tuner
|Full High Definition
|Playback Format (Visual)
|TV Features
|FHD Smart TV, Dolby Digital, Smart PVR
|Built-in Decoders
|Dolby Digital
|Power Consumption (kWh/yr)
|330 - kWh/yr, Based on 10 hrs/day
|Star Ratings
|4 Stars
|Product Width (cm)
|Product Depth (cm)
|Product Height (cm)
|Weight (kg)
|Manufacturers Express Warranty (months)
If you feel your product has failed a Consumer Guarantee (as defined by Australian Consumer Law) then don't worry you can easily return it to your local Harvey Norman store. We'll even pay for the postage if you live in an area where there is no store. Our returns policy covers any purchased item (conditions apply).
tcl 50 s4800fs full hd led lcd smart tv is rated out of 5 by 1.
Rated 5 out of 5 by kiastra from Excellent Loving the size and wifi capabilities of this smart tv
Date published: 2017-01-28
Protect your purchase with Product Care®. Get a brand new replacement if your product suffers an eligible fault through our hassle free support process, plus enjoy a range of exclusive benefits like a product health check and free prints each year so you experience your new product even more.
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More Videos...
2016 Nissan Maxima SR - Redline: Review
As the flagship sedan in the Nissan family, the sleek 2016 Maxima has some pretty high expectations for setting the standard within the lineup. This all-new version starts off on the right track with a potent 300 horsepower V6, a bold design, and luxurious cabin furnishings. Just keep in mind, this may or may not be the 4-door sports car that Nissan is promising.
2002 Nissan Maxima: How to clean the MAF and Throttle Body
Enjoyed the video or found it helpful? feel generous? you can donate on the main channel page. Thanks for watching! THIS WAS ACTUALLY A CLUTCH ISSUE. $800 DOWN FOR A NEW CLUTCH AND MY CAR IS WORKING WELL! Replacement Clutch: http://goo.gl/YyM06i Used in the video Socket Set: http://goo.gl/7K00r4 MAF and throttlbe body cleaner: http://goo.gl/mffeIK MAF sensor: http://goo.gl/OlrgfV This video will show you how to clean the MAF and Throttle Body on a 2002 Nissan Maxima. This is a very simple process but it could give your car more power when it's missing it. This personally didn't fix my issue as it seems to be a clutch / transmission problem but at least I'm happy to make a new tutorial for my viewers.
02' Maxima Before & After Exhaust
02' Nissan Maxima, Injen CAI, Custom 2.5" Catback with 12" Glasspack Muffler www.texas-racing.com
Marty's New Nissan
An MCM Fan demanded that Moog buy Marty a JDM, 2 door turbo charged Nissan, so thats exactly what Moog did... Get mad MCM Stickers, music and other stuff here: http://www.mightycarmods.com/collections/all Keep up to date with all things MCM here: http://www.facebook.com/mightycarmods Discuss this episode here: http://forums.mightycarmods.com/showthread.php?28384-Martys-Nissan-Revealed &p=495286#post495286


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We aim to understand how telomeres solve the end-protection problem. Specifically, this proposal describes experiments to gain insight Into the mechanism by which the telomeric protein complex, shelterin, represses the two main DNA repair reactions, NHEJ and HDR at chromosome ends.
Our aim I s to delineate the nature of the repair reactions at telomeres, their outcomes, what factors are involved, how these pathways are regulated, and how telomeres prevent inappropriate pnscessing by repair pathways. Telomere dysfunction is thought to be main source of genome instability in human cancer, has been implicated in aging, and is at the core of several human diseases that are caused by loss of telomeric DNA (e.g. dyskeratosis congenita, anaplastic anemia). When telomeres become dysfunctional, inappropriate repair at chromosome ends is a major determinant of the pathological outcomes. Detailed understanding of the repair pathways at dysfunctional telomeres is therefore expected to impact the treatment and prevention human disease. We will use genetic, molecular genetic, and cell biological techniques to address the mechanism by which telomeres repress inappropriate repair and define the pathological repair reactions at dysfunctional telomeres. The experimental approaches will involve the tools for studying mammalian telomeres that we have developed under the auspices of this grant over the past 16 years. Specifically, we will use mouse embryo fibroblast cell lines from which shelterin components can be deleted with the Cre recombinase. By changing the genetic background of these cells, using compound genotypes, we can monitor the repair at dysfuncUonanl telomere, delineate the genes involved In the reactions, and define how shelterin represses these reactions at functional telomeres.
; A growing number of human disease states are now understood to involve a failure in the function of telomeres, the protective elements at the ends of human chromosomes. This project is aimed at gaining Insight into how telomeres protect chromosome ends and what happens when this protection is lost. The work is expected to be significant in the context of cancer, aging, and telomere-related diseases such as dyskeratosis congetica.
|Frescas, David; de Lange, Titia (2014) A TIN2 dyskeratosis congenita mutation causes telomerase-independent telomere shortening in mice. Genes Dev 28:153-66
|Frescas, David; de Lange, Titia (2014) TRF2-tethered TIN2 can mediate telomere protection by TPP1/POT1. Mol Cell Biol 34:1349-62
|Zimmermann, Michal; de Lange, Titia (2014) 53BP1: pro choice in DNA repair. Trends Cell Biol 24:108-17
|Kabir, Shaheen; Hockemeyer, Dirk; de Lange, Titia (2014) TALEN gene knockouts reveal no requirement for the conserved human shelterin protein Rap1 in telomere protection and length regulation. Cell Rep 9:1273-80
|Frescas, David; de Lange, Titia (2014) Binding of TPP1 protein to TIN2 protein is required for POT1a,b protein-mediated telomere protection. J Biol Chem 289:24180-7
|Zimmermann, Michal; Lottersberger, Francisca; Buonomo, Sara B et al. (2013) 53BP1 regulates DSB repair using Rif1 to control 5' end resection. Science 339:700-4
|Doksani, Ylli; Wu, John Y; de Lange, Titia et al. (2013) Super-resolution fluorescence imaging of telomeres reveals TRF2-dependent T-loop formation. Cell 155:345-56
|Ahmed, Emad A; Sfeir, Agnel; Takai, Hiroyuki et al. (2013) Ku70 and non-homologous end joining protect testicular cells from DNA damage. J Cell Sci 126:3095-104
|Lottersberger, Francisca; Bothmer, Anne; Robbiani, Davide F et al. (2013) Role of 53BP1 oligomerization in regulating double-strand break repair. Proc Natl Acad Sci U S A 110:2146-51
|Takai, Kaori K; Kibe, Tatsuya; Donigian, Jill R et al. (2011) Telomere protection by TPP1/POT1 requires tethering to TIN2. Mol Cell 44:647-59
Showing the most recent 10 out of 28 publications


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More Videos...
EF Turbo
This is the first time I have turbo'd a EF falcon and this is the first start. I have a few little problems, I broke my fuel pressure reg putting the motor in the car and I have a small oil leak out of the oil turbo feed (just needs to be tightened) I have a fuel leak from under the car but have fixed that now. 16psi revving to 4000revs not to bad.
ONERAT Turbo EL XR6 Falcon Powercruise 44 Perth 2013
Another compilation of videos, which my brother filmed with his EOS650D Racing, drifting and cruising at Powercruise #44 EL XR6 turbo Falcon - 500rwhp through Astro Performance A5 manual trans
Motorvation 2013 - EL Falcon
Motorvation 2013 - EL Falcon
1000hp Ford XR6 Turbo Engine
Nizpro 1000hp XR6 turbo Engine. Australian Car, Australian Company. 1000hp 4.0ltr 6cyl Ford.


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Peanut Butter And Jelly Cheesecake
|1 Cup (16 tbs) (Old Fashioned / Quick Cooking)
|Chopped peanuts
|1⁄4 Cup (4 tbs)
|Packed brown sugar
|3 Tablespoon
|3 Tablespoon, melted
|Cream cheese
|16 Ounce, softened (2 Packages, 8 Ounce Each)
|Granulated sugar
|1 Cup (16 tbs)
|Chunk style peanut butter
|1⁄2 Cup (8 tbs)
|3 Tablespoon
|1⁄2 Cup (8 tbs)
|Grape jelly
|1⁄2 Cup (8 tbs)
Combine oats, peanuts, brown sugar and margarine; press onto bottom of 9-inch springform pan.
Bake at 325°, 10 minutes.
Combine cream cheese, granulated sugar, peanut butter and flour, mixing at medium speed on electric mixer until well blended.
(Batter will be very stiff.) Add eggs, one at a time, mixing well after each addition.
Blend in milk; pour over crust.
Bake at 450° 10 minutes.
Reduce oven temperature to 250°; continue baking 40 minutes.
Loosen cake from rim of pan; cool before removing rim of pan.
Stir jelly until smooth; drizzle over cheesecake in criss-cross pattern to form lattice design.
Chill until firm.
Recipe Summary
Rate It
Nutrition Rank
Nutrition Facts
Serving size: Complete recipe
Calories 5016 Calories from Fat 2676
% Daily Value*
Total Fat 308 g473.8%
Saturated Fat 117 g585.1%
Trans Fat 0 g
Cholesterol 1356.1 mg452%
Sodium 2483.3 mg103.5%
Total Carbohydrates 472 g157.4%
Dietary Fiber 30.3 g121.3%
Sugars 313.6 g
Protein 126 g251.9%
Vitamin A 168.7% Vitamin C 0.08%
Calcium 89.7% Iron 105.3%
*Based on a 2000 Calorie diet


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Disney's animated hit "Frozen" is going to China.
The studio said Sunday that China Film Group, the government agency and gatekeeper for non-domestic films looking for a shot at the world's second-largest movie market, had indicated it would allow a 2014 release for Disney Animation's 3D family film. No date has been set.
Also read: 'Frozen' Review: Disney's Best Animated Musical Since 'Beauty and the Beast' (Video)
It was great weekend overall for "Frozen," especially overseas, where it brought in $35 million from 33 markets in its fourth week. Included was a No. 1 debut in Mexico, where its $5.5 million opening weekend nearly doubled that of another Disney animated hit, "Tangled."
The top markets for "Frozen" so far include Germany ($26.4 million), the U.K. ($26.3 million), France ($21.2 million), Russia ($19.6 million) and Spain ($12 million.)
The international haul for "Frozen" is up to $152.6 million and its global total, including a $19.1 million fifth week in the U.S., stands at $344.1 million.
The post Disney's 'Frozen' to Play at China Box Office appeared first on TheWrap.
Related stories from TheWrap:
'Hobbit' Fans Halt a Fearsome Tram in 'Lord of the Rings' Prank
Joaquin Phoenix's 'Her' Logs On With $42K Per Screen in Limited Box-Office Opening
Bilbo Bags Burgundy at Box Office as 'Hobbit' Surges Past 'Anchorman 2'


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Broken Bucks: Money Funds that Took Taxpayer Guarantees in 2008
Linus Wilson
University of Louisiana at Lafayette - College of Business Administration
August 28, 2015
This is the first study to look at the characteristics of funds accepting the $2.7 trillion taxpayer guarantee of money market mutual funds during the 2008 financial crisis. Funds with lower asset maturities were significantly less likely to need federal or sponsor bailouts. Fund shares that benefited from Federal Reserve's asset-backed commercial paper program were significantly more likely to get bailed out by taxpayers and sponsors. Finally, the paper tests if funds adhering to the SEC's 2010 liquidity reforms prior to their enactment were less likely to be bailed out in 2008.
Number of Pages in PDF File: 42
Keywords: breaking the buck, bailout, Dodd-Frank, DLA, exchange rate stabilization fund, Financial Stability Oversight Council (FSOC), guarantees, liquidity, money market mutual funds, Primary Reserve Fund, regulation, SEC, Securities and Exchange Commission, U.S. Treasury, WAL, WAM, WLA
JEL Classification: G01, G18, G22, G23, G28, H12, H81, L5
Date posted: January 2, 2013 ; Last revised: August 29, 2015
Suggested Citation
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House reformed in 1985, which has 400 m2 on a plot of 1000 m2 . It is developed on 3 levels, with an orientation to the light.
Upon entering, a receiver with one bedroom with fitted wardrobes and the cozy living room, with a great fireplace, windows to enjoy the town and Montserrat. This room also accessed abroad through a large terrace.
On the same floor, kitchen with exit to the outside, a toilet and pantry.
Climbing is the rest area with 4 double bedrooms, with their wardrobes and terraces. Features master suite with full bath and its windows to the landscape. It has a bathroom for the rest of the rooms. In another plant the attic, with a double room with bathroom and another living room.
The exterior is formidable. Well-kept plot, garage for 2 cars and parking covered for 3 more. In another sector, excellent pool, spacious, air-conditioned and with barbecue integrated.
The outdoor area has independent access to the home and life of summer can be done without entering it since it has a kitchen, bathroom and a room for the rest. These latest facilities are integrated into the House and it can be the same internally.
As interesting fact can be accessed within walking distance to the castle of Gelida, that is claimed, its construction dates from the year 945 and leave you with some images. It is a really attractive area, fresh air, combination of charm, village near Barcelona and ancient with modern populations.
Ideal for big families or active social life. Schedule visit, surely you will love it!
Gelida is a municipality of the province of Barcelona (Catalonia, Spain), located on the eastern edge of the Barcelona region of the High Penedès . Borders to the North with San Hortóns Lorenzo and San Esteban de Sesrovires, Northeast with Castellví de Rosanes, East with Corbera de Llobregat, Southeast with Cervelló, to the South and Southwest with Subirats, and San Sadurní de Noya in a small strip to the West. The capital of the district is Villafranca del Panadés.
Its more than 7,000 inhabitants develops his life with all the services, schools, institutes, etc. It is 25 minutes far from Barcelona by motorway or 30 minutes by adjacent towns.
Availability upon agreement. This material is based upon information, which we consider reliable, but because third parties have supplied it, we cannot represent that it is accurate or complete, and it should not be relied upon as such. This offering is subject to errors, omissions, and change of price or withdrawal without notice. Taxes, notary and register fees must be paid by purchaser, the commission by the seller as stipulated by Spanish regulations.


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Photo: Oxmoor House
The delicate, subtle flavors of roasted pistachios and lavender honey transform this baked grouper into an easy, yet refined meal that family and friends will remember. Serve with sautéed spinach.
Prep: 12 minutes; Cook: 12 minutes
4 servings (serving size: 1 fillet and about 1 tablespoon sauce)
More from Oxmoor House
Recipe Time
Prep: 14 Minutes
Cook: 14 Minutes
Nutritional Information
Calories 337
Caloriesfromfat 33 %
Fat 12 g
Satfat 4.7 g
Monofat 4.3 g
Polyfat 2.3 g
Protein 37.7 g
Carbohydrate 18.1 g
Fiber 1.5 g
Cholesterol 78 mg
Iron 2.4 mg
Sodium 360 mg
Calcium 26 mg
5 tablespoons dry breadcrumbs
5 tablespoons finely chopped unsalted shelled dry-roasted pistachios
4 (6-ounce) grouper fillets
1/4 teaspoon salt
1/4 teaspoon freshly ground black pepper
2 large egg whites, lightly beaten
Lemon wedges (optional)
Lavender sprigs (optional)
1. Preheat oven to 450°.
2. Combine breadcrumbs and pistachios in a shallow dish. Sprinkle fillets evenly with salt and pepper. Dip fillets in egg whites; dredge in breadcrumb mixture.
3. Place fish on a jelly-roll pan lined with parchment paper; bake at 450° for 12 minutes or until fish flakes easily when tested with a fork or until desired degree of doneness. Drizzle fillets evenly with Lavender Honey Sauce. Garnish with lemon wedges and lavender sprigs, if desired.
April 2009


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INDIANAPOLIS, Friday, Nov. 21, 2003 - The 88th running of the Indianapolis 500-Mile Race will follow the event's traditional three-week format, with Opening Day at the Indianapolis Motor Speedway scheduled for Sunday, May 9, 2004, and nearly a...
INDIANAPOLIS, Friday, Nov. 21, 2003 - The 88th running of the Indianapolis 500-Mile Race will follow the event's traditional three-week format, with Opening Day at the Indianapolis Motor Speedway scheduled for Sunday, May 9, 2004, and nearly a month of pageantry and on-track action will culminate with Race Day on Sunday, May 30.
Opening Day will feature special ceremonies and the first Indy Racing League(R) IndyCar(R) Series official practice of the event. Practice continues daily from May 10-14.
Qualifications start Saturday, May 15 with the drama of Pole Day. Drivers will aim to capture the coveted MBNA Pole Award and its accompanying bonus and other prizes. Second Day Qualifying takes place Sunday, May 16.
There will be no track activity May 17-18, but the track will re-open May 19-22 for four days of practice leading up to the thrilling final day of qualifying, Bump Day, Sunday, May 23.
The second annual Freedom 100 event for the IRL Menards Infiniti Pro SeriesTM is scheduled for Saturday, May 22. It's the premier event for the Indy Racing League development series, featuring many Indianapolis 500 stars of the future.
While there will be no IndyCar Series on-track activity May 24-26, the Indianapolis Motor Speedway again will play host to the popular 500 Festival Community Day on Wednesday, May 26, featuring track laps for the public in their passenger cars, a driver autograph session and other family-oriented activities.
Miller Lite Carb Day, the final practice session for the starting field of 33, takes place Thursday, May 27. Fans also will see the action-packed 28th annual Checkers/Rally's Pit Stop Challenge in which top race teams compete for the right to become "The Fastest Crew at Indy." Miller Lite Carb Day will end with the Carb Day Concert.
Race Day for the 88th Indianapolis 500 will be Sunday, May 30. The green flag for the "Greatest Spectacle in Racing" will drop at 11 a.m. (Indianapolis time). It will be broadcast live on ABC-TV and the IMS Radio Network.
While the schedule follows a traditional format, the 88th year of activities at the Indianapolis Motor Speedway will be anything but routine. The theme for this year's event is Lights, Camera, Traction! in a salute to the star power and drama of the event and its drivers, and a number of IndyCar Series stars will attempt to put their mark on history.
Two-time IRL IndyCar Series champion Sam Hornish Jr. returns to Indy with a new look, in the famous red-and-white colors of Penske Racing, the most successful team in Indianapolis 500 history with 13 victories. His Marlboro Team Penske teammate, Helio Castroneves, will attempt to win his third Indianapolis 500 in four years.
Castroneves has the best finishing record in history of any driver in his first three races at the famous 2.5-mile oval, having finished first, first and second, respectively, from 2001-03. He won the pole in 2003.
Another favorite for the 2004 Indianapolis 500 crown will be Scott Dixon, the 2003 IndyCar Series champion. Dixon scored nine top-five finishes in 16 races in 2003 but finished a disappointing 17th at Indy due to a late-race accident. He will return to Indy in 2004 with the Target Chip Ganassi Racing team with teammate Darren Manning, an Indianapolis rookie.
Tickets are available for the 2004 Indianapolis 500-Mile Race. For information on tickets, parking and camping, log on to www.indianapolismotorspeedway.com or call the Speedway ticket office at (317) 492-6700 or (800) 822-INDY.
88th INDIANAPOLIS 500 SCHEDULE:
Sunday, May 9
Opening Day Practice
May 10-14
Saturday, May 15
Pole Day (MBNA Pole Qualifying, practice)
Sunday, May 16
Second-day qualifying
May 17-18
No track activity
May 19-22
Saturday, May 22
Freedom 100 race for the Menards Infiniti Pro Series
Sunday, May 23
Bump Day (Final day of qualifying)
May 24-25
No track activity
Wednesday, May 26
500 Festival Community Day
Thursday, May 27
Miller Lite Carb Day (Final practice, Checkers/Rally's Pit Stop Challenge, concert)
Friday, May 28
No track activity
Saturday, May 29
Public Drivers' Meeting, 500 Festival Parade
Sunday, May 30
88th Indianapolis 500-Mile Race


text:
Forum/Town Hall: Vision Zero Town Hall
East 69th Street between Lexington Ave. and Park Ave.
New York, NY 10021
related issues:
In New York City, approximately 4,000 New Yorkers are seriously injured and more than 250 are killed each year in traffic accidents. The Vision Zero Action Plan is the City's framework for ending traffic deaths and injuries on the streets.
Tuesday, June 24th, Sen. Krueger will be hosting a Vision Zero Town Hall Presentation and Discussion on improving street safety in our community, along with Councilmembers Dan Garodnick and Ben Kallos and the New York City Department of Transportation. Additional participants will include the Office of the Mayor, the NYPD, local community boards, and Transportation Alternatives.
Join us to learn more about the plan, share your ideas about how to improve street safety, and help us identify dangerous locations in our neighborhoods.
How a Bill Becomes LawLearn More
Senator has new policy idea
Idea is drafted into a Bill
Bill undergoes committee process
Senate and Assembly pass bill
Bill is signed by Governor


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The general trademark of a manufacturer by which the consumer knows its products. A manufacturer can have multiple brand names. Some manufacturers license their brand names to other producers.Lenovo
Product family:
The product family is a generic trademark of a brand to indicate a very wide range of products, that can encompass multiple categories. We include product family in the Icecat product title.ThinkCentre
Product series:
Product series is a brand's indication, often indicated by round numbers like 3000, that identifies a group of products within one category that are technically very similar. We don't include product serie in the Icecat product title on a product data-sheet to avoid confusion.E
Product name:
Product name is a brand's identification of a product, often a model name, but not totally unique as it can include some product variants. Product name is a key part of the Icecat product title on a product data-sheet.ThinkCentre E50
Product code :
The brand's unique identifier for a product. Multiple product codes can be mapped to one mother product data-sheet if the specifications are identical. We map away wrong codes or sometimes logistic variants.POWDAUK
Category :
Personal Computers, PCs for short, are computers for personal usage. They always have the following components:\PCs/workstations
- A processor (CPU), this is the heart of your computer, where the data processing is done.\
- Memory (RAM), this is very fast memory in which temporary data is stored before being processed by the processor.\
- Motherboard, this is the component that connects all the different parts of your computer. Often it has some integrated components like a sound card, enabling your computer to play sound, or a network card, to connect your computer to the network.\
- Video board, this is the part of your computer that is responsible for the graphics processing. Micro ATX motherboards often have an integrated video board. Those integrated video boards are generally not very well suited for playing games, but good enough for watching movies.\
- Hard disk, this is the permanent memory of your computer where your data is stored.\
- An optional DVD/CD player/recorder for reading/writing D
- A processor (CPU), this is the heart of your computer, where the data processing is done.\
- Memory (RAM), this is very fast memory in which temporary data is stored before being processed by the processor.\
- Motherboard, this is the component that connects all the different parts of your computer. Often it has some integrated components like a sound card, enabling your computer to play sound, or a network card, to connect your computer to the network.\
- Video board, this is the part of your computer that is responsible for the graphics processing. Micro ATX motherboards often have an integrated video board. Those integrated video boards are generally not very well suited for playing games, but good enough for watching movies.\
- Hard disk, this is the permanent memory of your computer where your data is stored.\
- An optional DVD/CD player/recorder for reading/writing D
Data-sheet quality: created/standardized by Icecat
The quality of the product data-sheet can be on several levels:
only logistic data imported: we have only basic data imported from a supplier, a data-sheet is not yet created by an editor.
created by Lenovo: a data-sheet is imported from an official source from a manufacturer. But the data-sheet is not yet standardized by an Icecat editor.
created/standardized by Icecat: the data-sheet is created or standardized by an Icecat editor.
only logistic data imported: we have only basic data imported from a supplier, a data-sheet is not yet created by an editor.
created by Lenovo: a data-sheet is imported from an official source from a manufacturer. But the data-sheet is not yet standardized by an Icecat editor.
created/standardized by Icecat: the data-sheet is created or standardized by an Icecat editor.
Included since: 20 Sep 2006
The date Icecat noticed for the first time that this product was included in the price list of a channel partner
Info modified on: 06 Feb 2017 12:03:02
The date of the most recent change of this product data-sheet in Icecat.
Product views: 24540
This statistic is based on the 66660 using ecommerce sites (eshops, distributors, comparison sites, ecommerce ASPs, purchase systems, etc) downloading this Icecat data-sheet since 20-09-06 Only sponsoring brands are included in the free Open Icecat content distribution as used by 64926 free Open Icecat users .
Warranty: One year parts and labour, Onsite Repair.
Long product name Lenovo ThinkCentre E50 2.8GHz Tower PC:
The short editorial description of Lenovo ThinkCentre E50 2.8GHz Tower PCThinkCentre E50, Intel® Celeron® D Processor 336, 512MB, 80GB 7200RPM S-ATA HDD, no diskette drive, PCI/AGP Tower (4x4), SiS 661FX, 16x DVD-ROM, Realtek 10/100 Ethernet, Windows XP Professional
Marketing text Lenovo ThinkCentre E50 2.8GHz Tower PC:
The official marketing text of Lenovo ThinkCentre E50 2.8GHz Tower PC as supplied by the manufacturerThe low price tag doesn't mean you compromise on features. The ThinkCentre E50 offers essential business features for exceptional value. ThinkCentre E50 still includes all the added features you'd expect in a ThinkCentre - a durable steel easy to service chassis and Rescue-and-Recovery - one-button data recovery solution that allows you to get back to work quickly in event of a software crash or virus attack. Encased in a new design, the ThinkCentre E50 delivers proven technologies and data protection to simplify manageability throughout the ownership experience.
Short summary description Lenovo ThinkCentre E50 2.8GHz Tower PC:
This short summary of the Lenovo ThinkCentre E50 2.8GHz Tower PC data-sheet is auto-generated and uses the product title and the first six key specs.Lenovo ThinkCentre ThinkCentre E50, Intel® Celeron®, DDR-SDRAM, 2x DIMM, Serial ATA, DVD-ROM, MiRage
Long summary description Lenovo ThinkCentre E50 2.8GHz Tower PC:
This is an auto-generated long summary of Lenovo ThinkCentre E50 2.8GHz Tower PC based on the first three specs of the first five spec groups.Lenovo ThinkCentre E50, ThinkCentre. Processor family: Intel® Celeron®. Internal memory type: DDR-SDRAM, Memory slots: 2x DIMM. Hard drive interface: Serial ATA. Optical drive type: DVD-ROM. Discrete graphics adapter model: MiRage
This is a demo of a seamless insert of an Icecat LIVE product data-sheet in your website. Imagine that this responsive data-sheet is included in the product page of your webshop. How to integrate Icecat LIVE JavaScript.
Processor frequency*
The speed that the microprocessor executes each instruction or each vibration of the clock. The CPU requires a fixed number of clock ticks, or cycles, to execute each instruction. The faster the clocks rate, the faster the CPU, or the faster it can execute instructions. Clock Speeds are usually determined in MHz, 1 MHz representing 1 million cycles per second, or in GHz, 1 GHz representing 1 thousand million cycles per second. The higher the CPU speed, the better a computer will perform.
2.8 GHz
Processor family*
A family of processors is a group of processors produced by one company over a short period of time e.g. Intel Pentium processors.
Intel® Celeron®
Processor front side bus
A computer communications interface used to connect the processor to the rest of the computer, except the cache (and possibly other processors).
533 MHz
Internal memory*
A computer's memory which is directly accessible to the CPU.
Internal memory type*
The type of internal memory such as RAM, GDDR5.
Maximum internal memory*
The maximum internal memory which is available in the product.
Memory slots
Number and type of memory expansion slots, including connector and memory module descriptions.
2x DIMM
Total storage capacity*
The total amount of data that can be stored on the device.
Hard drive interface
The way that a hard disk drive (HDD) is connected to the rest of the computer through a 'bus' such as ATA or SCSI.
Serial ATA
Hard drive speed
The rotational speed of a hard disk expressed in rotations per minute. The faster the better.
Optical drive
Optical drive type*
An optical drive uses laser to read optical discs such as CDs, DVDs and Blu-Ray. Some types of optical drive are: CD ROM drive, CR-RW (CD writer) drive, DVD-ROM.
DVD read speed
Discrete graphics adapter model*
A graphics adapter (often known as a video card) generates images for a display. A discrete graphics adapter plugs into the motherboard, and usually produces much better graphics than an integrated graphics adapter. There are various models of discrete graphics adapters.
Operating system installed*
Type of operating system on a device e.g. IOS on Apple devices, Android for mobile devices.
Windows XP Professional
Ports & interfaces
USB 2.0 ports quantity*
Number of USB 2.0 ports (connecting interfaces) in the device. USB 2.0 was released in April 2000 (now called "Hi-Speed"), adding higher maximum signaling rate of 480 Mbit/s (effective throughput up to 35 MB/s or 280 Mbit/s), USB 2.0 ports are usually black.
VGA (D-Sub) ports quantity*
Number of VGA (D-Sub) ports (connecting interfaces) in the device. The VGA (D-Sub) connector is a 15 pin connector between a computer and a monitor. It was first introduced in 1987 by IBM.
PS/2 ports quantity
The number of PS/2 connectors for keyboards and mice. Its name comes from the IBM Personal System/2.
Ethernet LAN (RJ-45) ports*
Number of Ethernet LAN (RJ-45) ports (connecting interfaces) in the device. Ethernet LAN (RJ-45) ports allow a computer to connect to the ethernet.
Ports & interfaces
Microphone in *
The socket where a microphone is connected to the device.
Headphone outputs *
Number of sockets /ports where headphones are connected.
Serial ports quantity
The number of serial ports in a computer or peripheral. A serial port is a serial communication physical interface through which information transfers in or out one bit at a time. The term "serial port" usually identifies hardware more or less compliant to the RS-232 standard, intended to interface with a modem or with a similar communication device. In modern computers and peripherals, serial ports have largely been replaced by USBs and other interfaces.
Parallel ports quantity
The number of parallel ports. Parallel ports, also known as printer ports, are a type of interface found on computers (personal and otherwise) for connecting peripherals. In computing, a parallel port is a parallel communication physical interface. Parallel ports were common in the 1980s and '90s (mostly conforming to industry standard IEEE 1284) but are now being replaced by USBs and other ports.
Chassis type *
The type of rigid framework onto which is the hosuing for device components.
Product type *
The sub-category of the product.
Audio system
System used to play music or speech.
Power supply *
The way in which the product is powered e.g. rechargeable battery, mains electricity connected via a plug and cable.
Weight & dimensions
Width *
The measurement or extent of something from side to side.
180 mm
Depth *
The distance from the front to the back of something.
445 mm
Height *
The measurement of the product from head to foot or from base to top.
392 mm
Weight *
Weight of the product without packaging (net weight). If possible, the net weight is given including standard accessories and supplies. Please note that sometimes the manufacturer leaves out the weight of accessories and/or supplies.
9.2 kg
Packaging content
Display included *
This product includes a display.
Bundled software
Software distributed with another product such as a piece of computer hardware or other electronic device, or a group of software packages which are sold together. A software suite is an example of bundled software, as is software which is pre-installed on a new computer.
Adobe Acrobat Reader, Diskeeper Lite from Diskeeper, Google Desktop, Google Picasa 2, Google Toolbar, InterVideo WinDVD, Lotus Notes Stand-alone Client (license), Lotus SmartSuite Millennium edition (license), PC-Doctor diagnostics, Symantec Client Security 3.0 (with 90 days of virus definitions), ThinkVantage Productivity Center, ThinkVantage Rescue and Recovery, ThinkVantage System Update
Other features
Networking features
Ethernet/Fast Ethernet
Diskette drive


text:
Are you looking for industrial trucks? Hotfrog showcases more than 1,000 popular businesses related to industrial trucks! To find more business related to industrial trucks, use the left navigation menu.
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Racine, WI
Schmidt Industrial Truck is a forklift & material handling equipment dealer - new, used, parts and service
Porterville, CA
Hotfrog US provides information regarding Valley Industrial Truck Service in Porterville CA. Valley Industrial Truck Service is located at 1113 Merrill Ave and provides Industrial Machinery and Vehicle services. Contact …
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Jungheinrich has evolved from a manufacturer of industrial trucks to a manufacturing logistics service provider Jungheinrich distributed in the United States by MCFA MCFA and Jungheinrich Enter Into North Am…
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Hilo Industrial Trucks sells new & used forklifts, material handling equipment, sweepers/scrubbers in Long Island. Parts & service, equipment rentals and warehousing solutions also available
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Rightway Truck N Trailer in Porter, IN is a repair shop for commercial and industrial trucks and trailers
Martinsville, NJ
Forklift Operator Training, Licensing, and Management. Fork Truck Instruction,OSHA Powered Industrial Truck Compliance and Evaluation
Forklift Safety
Portland, ME
Gregory Industrial Trucks manufactures Material Handling Equipment for use in explosive and hazardous environments
Ul StandardsElectric ForkliftLift TruckForklift Trucks
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Oklahoma City, OK
Perfection Truck Parts & Equipment | A leading distributor of industrial truck parts & equipment
Fresno, CA
Welcome to TruckWasherPro.com. Your online source for heavy duty, industrial truck washing supplies
Elon, NC
Keep your trucks moving along with used OTR tires and industrial truck rims from us in Elon, North Carolina
haverhill, ma
Reith Industrial Truck (Haverhill, MA) specializes in the sales and service of used and reconditioned forklift equipment. We service all makes and models of fork lifts including pneumatic tire, cushion tire, narrow aisle…
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Wilmington, MA
Industrial truck service fork lift material handling equipment company in Wilmington MA. fork lift sales rentals and service TUSK Lift Trucks Rol-Lift Industrial Trucks
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Stafford Springs, CT
Northeast Industrial Park deals with sales, rentals, parts, & service of industrial trucks in the Stafford Springs, CT area. 24-hr service. 8608519922
Forklift TrucksForklift Service
Hollywood, FL
Our qualified painters receive a monthly online training course on various topics related to and including the following: equipment safety, chemical safety, slip/trip/fall prevention, powered industrial truck safety…
Abbeville, SC
Weather it be the repair of a single hydraulic jack, or helping you to maintain an entire fleet of heavy equipment, we strive to make the best of every opportunity we are given Be it a single pallet jack or the…
Springfield, OH
The Higgins Group, Inc. is proud to be the promoter / facilitator for this SCCSC event. We aim to promote, in a fun & competitive environment, the safe & efficient operation of powered industrial trucks
Powered Industrial Trucks
College Park, MD
Over the road forklift, lift truck, boom and lift repairs and service. Lift gate installations, mobile tire press and battery services. Service in MD, DC and Baltimore
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New Berlin, WI
Badger Toyotalift specializes in new and used lift trucks, rentals, parts and service, training and lift truck safety products
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Meadville, PA
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Dayton, OH
Robert's on sight welding with 10+ years experience at Fabrication & Repairs for Commercial & Residental... If you need anything welded General and heavy equipment repairs Railing, gate, and fire escape repairs S…
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Powerful AWD Aircraft tugs, aircraft pushbacks, aircraft tow tractors, aircraft tractors, and aircraft pushers. Click here
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text:
Makes About 20 Servings
Our own Joyce McClelland offers this recipe. It is so easy, it has become a favorite at our monthly employee birthday parties.
1/2 pound (2 sticks) margarine, softened
2 cups sugar
8 eggs
2 teaspoons vanilla extract
Two 16 ounce cans Hershey's
chocolate syrup
2 cups flour
3/4 cup milk
2 tablespoons margarine
3 cups sugar
2 cups semisweet chocolate chips
1 cup chopped walnuts
Preheat the oven to 325 degrees F. Grease a 13 x 18-inch sheet cake pan.
In a large bowl, cream together the margarine and sugar. Add the eggs and vanilla, and stir until blended. Add the chocolate syrup alternately with the flour, stirring until smooth after each addition.
Pour the batter into the prepared pan and bake for 30 minutes, or until a toothpick inserted in the center comes out clean. Cool the cake in the pan on a wire rack. Frost the cake in the pan while still warm.
To make the icing: Heat the milk in a heavy saucepan over medium heat. Melt the margarine in the milk, add the sugar, and stir to dissolve. Adjust the heat to medium-high for 30 seconds, until just boiling, then remove from the heat. Add the chocolate chips and beat by hand for 1 minute, until the chips are melted. Do not overbeat. Add the nuts, stir, and then frost the cake. Cut into 3-inch squares.
Not only is it possible to freeze nuts, but it is actually the preferred way to keep them. Most nuts will last up to six months in the freezer in sealed containers.
The Doughmakers Cookbook
125 Recipes for Success in Baking and Business
by Bette LaPlante and Diane Cuvelier
Hardcover; $24.95, $38.95 (CAN); 272 pages
Recipe reprinted by permission.
This page created June 2004
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Call (888) 651-9785
ar2 Australia
Our guide was very knowledgeable and we learnt the history of KL throughout the day.
It was a must for someone and #39;s first visit to KL. The tour included so many destinations I don and #39;t even know where to begin. The delicious lunch was a fusion of Chinese and Malay food.
An amazing tour, we really enjoyed!
Driver went over and above what we would have been happy with. Excellent explanations from a knowledgable guide. He also new where to go for great photos.
If you are spending a limited time in KL, this is the tour for you. Edwin is a very engaging guide, he accommodates himself to your pace and interests, and is full of information about general topics about the city and life within it. It is a well constructed tour, each location building on the next. The museum visits sets you up for the rest of the day, little India is indeed very little it could be a drive by to be honest, and the Royal Selangor visit centre is a must. Thank you Edwin, a very enjoyable day.
Good to see both the modern and the old parts of KL and have a guide who went out of his way to tell us the history and development of the city. Enjoyed it very much and would recommend. And ... he suggested we went to China Town one evening for the experience, the shopping and the food - definately the best Chinese food weve tasted and great for people watching.
Highly Recommended
The local guide was amazing we were lucky enough to have the guide to ourselves so private tour it was.
His local knowledge and commentary was fanastic we had a wonderful day and would highly recommend to others.
We were picked up on the morning of our tour promptly. AND Private tour it was. Just the two of us with our guide Mr Lo.
He was so knowledgeable. It was great having a private tour as you can then go at your own pace.
We packed in so much on this tour. It was amazing.
We never would have seen half of the sights on our own and certainly would not have known the history behind different areas and buildings.
Can't recommend the private tour highly enough.
It's the best way to see the City all in one day.
Thanks Mr Lo.
This is the second Country I have booked trips with Viator for and can't fault any of the tours I have done.
Our recent holiday in KL was made even more enjoyable when we were shown the wonderful sights and sounds of the city by our very knowledgeable tour guide 'Bob'. Bob was a font of knowledge and gave an informative and at times very humorous commentary throughout our day long tour, simply the best, Thanks Bob!
Victoria and Wayne NSW Australia
The guide was great, very knowledgable
and the afternoon restaurant was so authentic to culture and local. The car was air conditioned , which was a big plus
Well worth trip. The guide was excellent. We saw everything there is to see in KL. Lunch was excellent as well. Strongly recommended.
Great day. The driver was on time, the van seated 6 of us comfortably and was air conditioned. The drivers english was great and he was very knowledgable.
Highly recommend this tour.
The tour and our guide Ravi were fantastic we saw all the sights of Kuala Lumpur and he was very friendly, informative and interesting.
Awesome tour, the guide was friendly and couldn't have been more helpful. Highly recommended.
The experience was very very spectacular. Our guide was very accommodating, pleasant and very knowledgable. He knew all his facts and whatever questions we posed to him he answered. He was very flexible in his approach. We thoroughly enjoyed our experience and would definitely recommend your company to our friends. Rob and Adele
The guide was amazing. Very knowledgable and obliging. Lunch was good but a bit spicy for our liking. The Batu Caves were the highlight but found the steps a challenge as I have recently had a total knee replacement but was well worth the effort to climb to the top. Overall an excellent and informative day. Would definitely recommend private tours if you like personal attention and flexibility.
The tour guide was very knowledable and he meet us at our hotel. He gave us excellent first hand knowledge on the history, cultural and evolution of modern day Kuala Lumpur. I would highly recommend this tour to anyone.
Our guide was fantastic. We would recommend this tour to everyone.
We were picked up from our hotel on time by our driver Sila. He was very informative and a safe driver. He let us view places as long as we wanted, we went to an Indian restaurant for lunch which was very nice, we had not eaten Indian before but he asked if we wanted to try it. We recommend going on a private tour as you are not tied to staying at places for a specified time as with a group. We had a lovely day.
Had a great day out in KL. The guide Mr Lo Lee Kiang was excellent - he knew exactly where to go and at what times in order to miss the crowds. He was very knowledgable on KL and Malaysia and we enjoyed it very much.
This was the best tour we've ever had. Our tour guide was great - really professional, friendly and well informed!
Michelle L Australia
This is a must for first timers in KL our guide was so informative and proud of his city a very interesting day .
It was a comprehensive tour, which gave us a perspective on the major sights of Kuala Lumpur. The guide was friendly and very good at giving us information on the landmarks we visited.
We had an excellent day tour. Our guide Ravi was very knowledgeable; we learned a lot about the country history, culture and main KL landmarks, much more than we ever could learn or see on our own. The lunch was a pleasant introduction for us to Malay/Chinese cuisine. This tour is definitely a must for the first time visitors.
We had a briliant day in Kula Lumpur , Suffian our guide for the day did a fantastic job, he kept us entertained with his knowlwdge and humour. Lunch was a treat at the Old China Cafe, we were sad when the day ended.
Thnaks again Suffian, will post some photos once we have downloaded them
Belinda and Richard
From UK
Don't think I could drive in this city - glad we had a tour guide. Got a really informative view of this lovely city and a great lunch as well.
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