Sorption of toxic heavy metals to soil

The surface soil is a major recipient of pollutants, including heavy metals, through atmospheric deposition, agricultural practices, and waste disposal. In the present work the sorption capacity of different types of soils to toxic heavy metals, i.e. chromium, copper, cadmium and lead has been studied. Experimental adsorption data for metals to the soil obtained by the batch method were fitted by linear isotherm. The various soils showed a very different behaviour in sorption of heavy metals. The distribution coefficient Kd, which is an indication of the adsorbing capacity of the substrate, varies within a wide range, from 57 to 53,000 l kg-1. Desorption of metals from the solid phase was found to be small, indicating that the soil matrix is affecting the metal mobility by modifying the bonding of pollutants to the soil system consequently affecting the potential for soil remediation processes.     

Detection of small genomic imbalances using microarray-based multiplex amplifiable probe hybridization

Array-based genome-wide screening methods were recently introduced to clinical practice in order to detect small genomic imbalances that may cause severe genetic disorders. The continuous advancement of such methods plays an extremely important role in diagnostic genetics and medical genomics. We have modified and adapted the original multiplex amplifiable probe hybridization (MAPH) to a novel microarray format providing an important new diagnostic tool for detection of small size copy-number changes in any locus of human genome. Here, we describe the new array-MAPH diagnostic method and show proof of concept through fabrication, interrogation and validation of a human chromosome X-specific array. We have developed new bioinformatic tools and methodology for designing and producing amplifiable hybridization probes (200-600 bp) for array-MAPH. We designed 558 chromosome X-specific probes with median spacing 238 kb and 107 autosomal probes, which were spotted onto microarrays. DNA samples from normal individuals and patients with known and unknown chromosome X aberrations were analyzed for validation. Array-MAPH detected exactly the same deletions and duplications in blind studies, as well as other unknown small size deletions showing its accuracy and sensitivity. All results were confirmed by fluorescence in situ hybridization and probe-specific PCR. Array-MAPH is a new microarray-based diagnostic tool for the detection of small-scale copy-number changes in complex genomes, which may be useful for genotype-phenotype correlations, identification of new genes, studying genetic variation and provision of genetic services.     

Differential effects of nebivolol and metoprolol on central aortic pressure and left ventricular wall thickness

The aim of this study was to investigate the effects of the vasodilating β-blocker nebivolol and the cardioselective β-blocker metoprolol succinate on aortic blood pressure and left ventricular wall thickness. We conducted a randomized, double-blind study on 80 hypertensive patients. The patients received either 5 mg of nebivolol or 50 to 100 mg of metoprolol succinate daily for 1 year. Their heart rate, central and brachial blood pressures, mean arterial pressure, augmentation index, carotid-femoral pulse wave velocity, and left ventricular wall thickness were measured at baseline and at the end of the study. Nebivolol and metoprolol significantly reduced heart rate, brachial blood pressure, and mean arterial pressure to the same degree. However, reductions in central systolic and diastolic blood pressures, central pulse pressure, and left ventricular wall thickness were significant only in the nebivolol group. The change in left ventricular septal wall thickness was significantly correlated with central systolic blood pressure change (r=0.41; P=0.001) and with central pulse pressure change (r=0.32; P=0.01). No significant changes in augmentation index or carotid-femoral pulse wave velocity were detected in either treatment group. This proof-of-principle study provides evidence to suggest that β-blockers with vasodilating properties may offer advantages over conventional β-blockers in antihypertensive therapy; however, this remains to be tested in a larger trial.     

Effect of Half-Marathon Running on Arterial Stiffness and Blood Biomarkers in High-Level and Recreational Male Athletes

There is no clear understanding about the effect of intensive physical load on arterial stiffness and related biomarkers. The aim of this study was to evaluate the effect of half-marathon running on arterial stiffness and blood biomarkers during post-competitive recovery period in competitive and recreational male athletes. Eleven high-level long-distance runners (27.1 ± 4.8 yrs) and seven recreational athletes (34.3 ± 6.1 yrs), who participated in a half-marathon run were examined. Blood biomarkers and arterial stiffness (SphygmoCor 7.1) were measured at baseline and at 18 to 22 hours after the competition. There were no statistically significant changes between the groups in augmentation index (AIx, )57@xIA or pulse wave velocities at carotid-femoral segment (cfPWV) during recovery period. Between-group comparison did not reveal significant differences in blood pressure and arterial stiffness values at baseline and during recovery period. The change of cfPWV (difference between cfPWV at baseline and cfPWV during post-competitive recovery period) was significantly dependent on race time and sports level of the athlete (high-level or recreational). A significant increase was found in hsCRP, creatine kinase and LDH activity during the post-race period in both groups. No significant changes were found in oxidative stress markers in the groups after the race except for higher diene conjugates level in recreational athletes in comparison with the high-level group during recovery period. Our study results showed that half-marathon competition did not cause any significant changes in arterial stiffness parameters during the recovery period. However, the change in cfPWV was independently associated with half-marathon race time and the athlete’s level of training revealing a mild increase of arterial stiffness in high-level athletes and athletes with a faster race time. Key points

• Half-marathon race did not cause significant changes in blood pressure and arterial stiffness parameters during post-competition recovery period in high-level and recreational athletes.
• The change of arterial stiffness after intensive half-marathon race depends on the training level of the athlete, revealing a mild increase of arterial stiffness in high-level athletes and athletes with a faster race time
• High-sensitivity CRP increased significantly during the recovery period in recreational and high-level athletes.
• Half-marathon running did not influence serum level of oxidative stress biomarkers except for higher diene conjugate concentration in recreational athletes as compared to high-level runners during recovery period.

Key words: Arterial compliance, elite athletes, physical load, oxidative stress, cardiovascular risk     

Impaired oxidative phosphorylation in overtrained rat myocardium

The present study was undertaken to characterize and review the changes in energy metabolism in rat myocardium in response to chronic exhaustive exercise. It was shown that a treadmill exercise program applied for six weeks led the rats into a state characterized by decreased performance, loss of body weight and enhanced muscle catabolism, indicating development of overtraining syndrome. Electron microscopy revealed disintegration of the cardiomyocyte structure, cellular swelling and appearance of peroxisomes. Respirometric assessment of mitochondria in saponin-permeabilized cells in situ revealed a decreased rate of oxidative phosphorylation (OXPHOS) due to diminished control over it by ADP and impaired functional coupling of adenylate kinase to OXPHOS. In parallel, reduced tissue content of cytochrome c was observed, which could limit the maximal rate of OXPHOS. The results are discussed with respect to relationships between the volume of work and corresponding energy metabolism. It is concluded that overtraining syndrome is not restricted to skeletal muscle but can affect cardiac muscle as well.     

Adiponectin is altered after maximal exercise in highly trained male rowers

The purpose of present study was to investigate plasma adiponectin response to acute exercise in highly trained male rowers. Ten rowers performed a maximal 6,000-m rowing ergometer test [mean performance time 20 min; 1,200.8 (29.9) s], and venous blood samples were obtained before, immediately after and after 30 min of recovery. In addition to adiponectin concentration, leptin, insulin, growth hormone and glucose values were measured. Adiponectin was not changed immediately after the exercise when uncorrected for plasma volume changes (–8.1%; P>0.05). However, adiponectin was decreased immediately after the exercise when adjusted for plasma volume changes (–11.3%; P<0.05). Adiponectin was significantly increased above the resting value after the first 30 min of recovery (uncorrected for plasma volume, +19.3%; corrected for plasma volume, +20.0%). No changes occurred in plasma leptin and insulin concentrations with exercise (uncorrected for plasma volume changes). While growth hormone and glucose values were significantly increased and decreased to the pre-exercise level immediately after the exercise and after the first 30 min of recovery, respectively (uncorrected for plasma volume changes), no differences in the responses to exercise were observed in these measured blood parameters when adjusting for plasma volume changes. There were no relationships between plasma adiponectin and other measured blood parameters before and after the exercise, nor were changes in adiponectin related to changes in other measured blood biochemical values after the exercise. These results suggest that plasma adiponectin is altered as a result of maximal acute exercise in highly trained athletes.     

Purification,Characterization and Plasma Half-Life of PEGylated Soluble Recombinant Non-HA-Binding CD44

Background and Objectives

The aim of this study was to increase the serum half-life of recombinant CD44 hyaluronan (HA) binding domain by PEGylation. We have previously found that recombinant soluble CD44 HA binding domain (CD44HABD) and its non-HA-binding triple mutant CD44HABD^R41AY78SY79S (CD44-3MUT) inhibits angiogenesis and subcutaneous tumor growth. However, this ~12 kDa recombinant protein displays a high serum clearance rate.

Methods

Here, we report the purification of monomeric CD44-3MUT from urea solubilized inclusion bodies using weak anion exchange chromatography and gel filtration. To increase the serum residence time of CD44-3MUT we PEGylated the resulting protein using 20 kDa methoxy-PEG-propionaldehyde.

Results

PEGylation of CD44-3MUT prolonged its in vivo serum half-life about 70-fold from 0.03 to 1.8 hours. Along with extended plasma residence time, PEGylation also increased the systemic exposure. By cell impedance assay we confirmed that PEGylated CD44-3MUT maintained its in vitro function. The results from the impedance assay additionally demonstrate that the CD44-3MUT effect on endothelial cells is mediated by vimentin.

Conclusions

In summary, we have developed a purification protocol for large-scale production of CD44-3MUT and generated a PEGylated form of CD44-3MUT. HA binding domain of CD44(CD44HABD) and its modified non-HA binding form (CD44-3MUT) inhibit angiogenesis and tumor growth in vivo without disturbing HA-binding functions. CD44-3MUT has been PEGylated for use as a new type of anti-angiogenic human drug. PEGylation of CD44-3MUT improved pharmacokinetic properties but retains its functional activity.     

Nebivolol and metoprolol: long-term effects on inflammation and oxidative stress in essential hypertension

Abstract Arterial hypertension is characterised by increased oxidative stress and inflammation, which are associated with further cardiovascular risk. The aim of our study was to investigate the long-term effects of nebivolol and metoprolol succinate on oxidative stress, and on inflammatory and pro-inflammatory markers in patients with hypertension. Eighty patients with never-treated mild-to-moderate essential hypertension, aged 30-65 years, were randomised to a 5 mg daily dose of nebivolol or a 50-100 mg daily dose of metoprolol succinate. Brachial blood pressure, plasma oxidized LDL (oxLDL), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), fibrinogen, intercellular adhesion molecule-1 (ICAM-1), asymmetric dimethylarginine (ADMA), and urine 8-isoprostane levels were measured before and after 1 year of treatment. Nebivolol and metoprolol reduced equally significantly brachial blood pressure. The oxLDL was significantly reduced in both groups (p 相似文献   

Association between asymmetric dimethylarginine and indices of vascular function in patients with essential hypertension

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is associated with endothelial dysfunction. The aim of the present study was to investigate the relationship between ADMA, indices of arterial stiffness, endothelial function and carotid artery intima-media thickness (IMT) in hypertension patients. Eighty middle-aged (47 ± 10 years) untreated patients with mild to moderate essential hypertension underwent routine physical examination, pulse wave analysis (PWA), measurement of aortic pulse wave velocity (PWV) and IMT. In PWA, administration of salbutamol and nitroglycerine was used to assess endothelium-dependent (EDV) and endothelium-independent vasodilation, respectively. In univariate analysis, ADMA was correlated with EDV (r = -0.26; p = 0.02) and IMT (r = 0.32; p = 0.007). In multiple regression analysis, ADMA was independently associated with the female gender, EDV, IMT and total cholesterol (R(2) = 0.30; p < 0.001). No correlation was detected between ADMA and augmentation index, central/brachial blood pressure or aortic PWV. In hypertension patients, ADMA is independently correlated with IMT and EDV. Thus, ADMA is a marker of endothelial dysfunction and intima-media thickening in patients with hypertension.