Machine learning model to predict vehicle electrification impacts on urban air quality and related human health effects.

Air pollution is a prevailing environmental problem in cities worldwide. The future vehicle electrification (VE), which in Europe will be importantly fostered by the ban of thermal engines from 2035, is expected to have an important effect on urban air quality. Machine learning models represent an optimal tool for predicting changes in air pollutants concentrations in the context of future VE. For the city of Valencia (Spain), a XGBoost (eXtreme Gradient Boosting package) model was used in combination with SHAP (SHapley Additive exPlanations) analysis, both to investigate the importance of different factors explaining air pollution concentrations and predicting the effect of different levels of VE. The model was trained with 5 years of data including the COVID-19 lockdown period in 2020, in which mobility was strongly reduced resulting in unprecedent changes in air pollution concentrations. The interannual meteorological variability of 10 years was also considered in the analyses. For a 70% VE, the model predicted: 1) improvements in nitrogen dioxide pollution (-34% to -55% change in annual mean concentrations, for the different air quality stations), 2) a very limited effect on particulate matter concentrations (-1 to -4% change in annual means of PM2.5 and PM10), 3) heterogeneous responses in ground-level ozone concentrations (-2% to +12% change in the annual means of the daily maximum 8-h average concentrations). Even at a high VE increase of 70%, the 2021 World Health Organization Air Quality Guidelines will be exceeded for all pollutants in some stations. VE has a potentially important impact in terms of reducing NO2-associated premature mortality, but complementary strategies for reducing traffic and controlling all different air pollution sources should also be implemented to protect human health.

The autism-associated Meis2 gene is necessary for cardiac baroreflex regulation in mice.

Recent understanding of Autism Spectrum Disorder (ASD) showed that peripheral primary mechanosensitive neurons involved in touch sensation and central neurons affected in ASD share transcriptional regulators. Mutant mice for ASD-associated transcription factors exhibit impaired primary tactile perception and restoring those genes specifically in primary sensory neurons rescues some of the anxiety-like behavior and social interaction defects. Interestingly, peripheral mechanosensitive sensory neurons also project to internal organs including the cardiovascular system, and an imbalance of the cardio-vascular sympathovagal regulation is evidenced in ASD and intellectual disability. ASD patients have decreased vagal tone, suggesting dysfunction of sensory neurons involved in cardio-vascular sensing. In light of our previous finding that the ASD-associated Meis2 gene is necessary for normal touch neuron development and function, we investigated here if its inactivation in mouse peripheral sensory neurons also affects cardio-vascular sympathovagal regulation and baroreflex. Combining echocardiography, pharmacological challenge, blood pressure monitoring, and heart rate variability analysis, we found that Meis2 mutant mice exhibited a blunted vagal response independently of any apparent cardiac malformation. These results suggest that defects in primary sensory neurons with mechanosensitive identity could participate in the imbalanced cardio-vascular sympathovagal tone found in ASD patients, reinforcing current hypotheses on the role of primary sensory neurons in the etiology of ASD.

Toward stomatal-flux based forest protection against ozone: The MOTTLES approach.

European standards for the protection of forests from ozone (O3) are based on atmospheric exposure (AOT40) that is not always representative of O3 effects since it is not a proxy of gas uptake through stomata (stomatal flux). MOTTLES "MOnitoring ozone injury for seTTing new critical LEvelS" is a LIFE project aimed at establishing a permanent network of forest sites based on active O3 monitoring at remote areas at high and medium risk of O3 injury, in order to define new standards based on stomatal flux, i.e. PODY (Phytotoxic Ozone Dose above a threshold Y of uptake). Based on the first year of data collected at MOTTLES sites, we describe the MOTTLES monitoring station, together with protocols and metric calculation methods. AOT40 and PODY, computed with different methods, are then compared and correlated with forest-health indicators (radial growth, crown defoliation, visible foliar O3 injury). For the year 2017, the average AOT40 calculated according to the European Directive was even 5 times (on average 1.7 times) the European legislative standard for the protection of forests. When the metrics were calculated according to the European protocols (EU Directive 2008/50/EC or Modelling and Mapping Manual LTRAP Convention), the values were well correlated to those obtained on the basis of the real duration of the growing season (i.e. MOTTLES method) and were thus representative of the actual exposure/flux. AOT40 showed opposite direction relative to PODY. Visible foliar O3 injury appeared as the best forest-health indicator for O3 under field conditions and was more frequently detected at forest edge than inside the forest. The present work may help the set-up of further long-term forest monitoring sites dedicated to O3 assessment in forests, especially because flux-based assessments are recommended as part of monitoring air pollution impacts on ecosystems in the revised EU National Emissions Ceilings Directive.

Health risk assessment of exposure to the Middle-Eastern Dust storms in the Iranian megacity of Kermanshah.

OBJECTIVE: This study assessed the effects of particulate matter (PM), equal or less than 10 µm in aerodynamic diameter (PM10), from the Middle-Eastern Dust events on public health in the megacity of Kermanshah (Iran). STUDY DESIGN: This study used epidemiological modeling and monitored ambient air quality data to estimate the potential PM10 impacts on public health. METHODS: The AirQ2.2.3 model was used to calculate mortality and morbidity attributed to PM10 as representative of dust events. Using Visual Basic for Applications, the programming language of Excel software, hourly PM10 concentrations obtained from the local agency were processed to prepare input files for the AirQ2.2.3 model. RESULTS: Using baseline incidence, defined by the World Health Organization, the number of estimated excess cases for respiratory mortality, hospital admissions for chronic obstructive pulmonary disease, for respiratory diseases, and for cardiovascular diseases were 37, 39, 476, and 184 persons, respectively, from 21st March, 2014 to 20th March, 2015. Furthermore, 92% of mortality and morbidity cases occurred in days with PM10 concentrations lower than 150 µg/m3. The highest percentage of person-days occurred for daily concentrations range of 100-109 µg/m3, causing the maximum health end-points among the citizens of Kermanshah. CONCLUSIONS: Calculating the number of cumulative excess cases for mortality or morbidity attributed to PM10 provides a good tool for decision and policy-makers in the field of health care to compensate their shortcomings particularly at hospital and healthcare centers for combating dust storms. To diminish these effects, several immediate actions should be managed in the governmental scale to control dust such as spreading mulch and planting new species that are compatible to arid area.

A multi-sites analysis on the ozone effects on Gross Primary Production of European forests.

Ozone (O3) is both a greenhouse gas and a secondary air pollutant causing adverse impacts on forests ecosystems at different scales, from cellular to ecosystem level. Specifically, the phytotoxic nature of O3 can impair CO2 assimilation that, in turn affects forest productivity. This study aims to evaluate the effects of tropospheric O3 on Gross Primary Production (GPP) at 37 European forest sites during the time period 2000-2010. Due to the lack of carbon assimilation data at O3 monitoring stations (and vice-versa) this study makes a first attempt to combine high resolution MODIS Gross Primary Production (GPP) estimates and O3 measurement data. Partial Correlations, Anomalies Analysis and the Random Forests Analysis (RFA) were used to quantify the effects of tropospheric O3 concentration and its uptake on GPP and to evaluate the most important factors affecting inter-annual GPP changes. Our results showed, along a North-West/South-East European transect, a negative impact of O3 on GPP ranging from 0.4% to 30%, although a key role of meteorological parameters respect to pollutant variables in affecting GPP was found. In particular, meteorological parameters, namely air temperature (T), soil water content (SWC) and relative humidity (RH) are the most important predictors at 81% of test sites. Moreover, it is interesting to highlight a key role of SWC in the Mediterranean areas (Spanish, Italian and French test sites) confirming that, soil moisture and soil water availability affect vegetation growth and photosynthesis especially in arid or semi-arid ecosystems such as the Mediterranean climate regions. Considering the pivotal role of GPP in the global carbon balance and the O3 ability to reduce primary productivity of the forests, this study can help in assessing the O3 impacts on ecosystem services, including wood production and carbon sequestration.

Co-expression of POU4F2/Brn-3b with p53 may be important for controlling expression of pro-apoptotic genes in cardiomyocytes following ischaemic/hypoxic insults.

Cardiomyocyte death following ischaemic/hypoxic injury causes irreversible damage to cardiac function and contributes to chronic diseases such as heart failure. Understanding the mechanisms associated with myocyte loss under these conditions can help to identify strategies to minimise/abrogate such detrimental effects. The p53 protein can induce apoptosis or cell cycle arrest, but effects on cell fate depend on interactions with other regulators such as POU4F2/Brn-3b (Brn-3b), which co-operates with p53 to increase the expression of pro-apoptotic genes. In contrast, the related POU4F1/Brn-3a (Brn-3a) blocks p53-mediated apoptosis but co-operates with p53 to enhance cell cycle arrest. In this study, we showed that permanent coronary artery ligation in mouse hearts, which induced apoptotic markers, activated caspase-3 and -8 and necroptosis markers; RIP-1 and -3 also increased Brn-3b and Brn-3a expression. However, Brn-3a was only detected in uninjured myocardium but not at the site of injury, whereas Brn-3b showed generalised increase, including within the infarct zone. Conversely, p53 was detected in the infarct zone and in some cells adjacent to the site of injury but not in uninjured myocardium. Co-localisation studies showed Brn-3a co-expression with p53 in cardiomyocytes adjacent to the infarct zone, whereas Brn-3b was co-localised with p53 in the infarct zone only. Increased Brn-3b and p53 correlated with elevated expression of pro-apoptotic target genes, Bax, Noxa and PUMA, whereas cleaved caspase-3 confirmed the presence of apoptotic cells within this region of the injured heart. Similarly, simulated ischaemia/reoxygenation (sI/R) injury in neonatal rat ventricular cardiomyocytes (NRVM) and heart derived H9c2 myoblasts increased Brn-3b, p53 as well as apoptotic genes, and this was associated with enhanced apoptosis. Furthermore, targeted reduction of Brn-3b using shRNA caused reduction in pro-apoptotic Bax and Noxa proteins, even though p53 expression remained intact, suggesting that Brn-3b is important for controlling the fate of the myocardium in the injured heart.

Impact of obesity on the prognostic value of the N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with acute myocardial infarction.

OBJECTIVE: To examine the influence of obesity on the predictive value of the pro-B-type natriuretic peptide (NT-proBNP) assay in acute myocardial infarction. DESIGN: Prospective observational study. SETTING: All intensive care units in one region of France. Patients 2217 consecutive patients admitted for an acute myocardial infarction matched with respect to age, gender, Killip class and renal function. MAIN OUTCOME MEASURE: Cardiovascular death at one year. RESULTS: There were three groups (according to body mass index (BMI): obese, overweight and normal) of 739 matched patients. Median levels of NT-proBNP were considerably lower in high BMI patients, by about 20% in overweight and by 60% in obese patients, compared with normal BMI patients. An inverse relationship between the propeptide values and BMI was found in the overall study population (r = -0.20, p < 0.0001), and for both genders. In multivariate linear regression, BMI as a continuous variable was a predictor of the log NT-proBNP level, even when adjusted for potential confounders. CV mortality at 1-year follow-up was similar for the three BMI groups (p = 0.691). In multivariate logistic regression analysis, log NT-proBNP predicted mortality in normal (OR (95% CI) 3.48 (2.00 to 6.12)) and overweight (OR (95% CI) 3.96 (1.95 to 8.06)) patients, even when adjusted for confounders (GRACE risk score, left ventricular ejection fraction). However, in obese patients, propeptide levels failed to retain their independent prognostic value (OR (95% CI) 1.34 (0.86 to 2.08)). CONCLUSIONS: In this large population of patients with myocardial infarction, circulating NT-proBNP levels were considerably lower in obese patients; the significance of the propeptide level as an independent prognostic factor is severely compromised.

Time course of asymmetric dimethylarginine (ADMA) and oxidative stress in fructose-hypertensive rats: a model related to metabolic syndrome.

OBJECTIVE: Asymmetric dimethylarginine (ADMA) is an endogenous modulator of endothelial function and oxidative stress, and increased levels of this molecule have been reported in some metabolic disorders and cardiovascular diseases. The aim of this work was to analyze the time course of dimethylarginine compounds and oxidative stress levels and the relationship between these and cardiovascular function in fructose-hypertensive rats. METHODS AND RESULTS: 90 male Sprague-Dawley rats were randomized into 2 groups, fed for 3 months with standard (C) chow supplemented or not with fructose (F, 60%). After sacrifice at different weeks (W), the aorta and plasma were harvested to assess the vascular and biochemical parameters. Our work showed that the plasma levels of ADMA in the fructose-fed rats increased after 2 weeks of the diet (1.6 ± 0.3 µM vs. 1.2 ± 0.3 µM, p < 0.05) with no changes in plasma levels of either SDMA or L-arginine and after an increase in glycemia. Levels of vascular oxidative stress, estimated in aortic segments using an oxidative fluorescence technique, were higher in the F group (W2: 1.14 ± 0.2% vs. 0.33 ± 0.02%, p < 0.01). An increase in expression levels of nitrotyrosine (3-fold) and iNOS (2-fold) were noted in the fructose-fed rats. After 1 month, this was associated with a significant increase in NAD(P)H oxidase activity. Concerning vascular function, a 15% decrease in maximal endothelium-dependent relaxation was found in the aorta of the F group. Our work showed that the presence of exogenous L-MMA, an inhibitor of NO synthase, was associated with a significant reduction in endothelium-dependent relaxation in isolated aorta rings of the C group; this effect was not observed in the vessels of fructose-fed rats. CONCLUSION: Our findings suggest that the elevated levels of ADMA observed could in part be secondary to the early development of oxidative stress associated with the development of hypertension.

The free oxygen radicals test (FORT) to assess circulating oxidative stress in patients with acute myocardial infarction.

BACKGROUND AND AIM: Reactive oxygen species (ROS) play an important role in the pathogenesis of many diseases including cardiovascular diseases. Several methods have been developed for the direct or indirect measurement of oxygen free radical and its by-products. The current study was designed to validate the new free oxygen radicals test (FORT) and to investigate the potential relationships between ROS and clinical or biological factors in male patients with acute myocardial infarction (AMI). METHODS: We analysed FORT values in samples from 66 patients with AMI. RESULTS: FORT values ranged from 324 to 1198 FORT units, with a median value of 581 (494-754) FORT units. In univariate analysis, FORT values were positively related only to LVEF <40% (p=0.005), levels of CRP (r=0.438, p<0.001) and peak CK (r=0.274, p=0.028). Multiple linear regression analysis showed that CRP (p=0.023), LVEF <40% (p<0.001) and the presence of diabetes (p=0.039) were independent predictors of serum FORT values. This statistical model can explain 45% of the variance in FORT values (R(2)=0.45). CONCLUSIONS: The FORT is a simple tool to assess circulating ROS in routine clinical practice. Oxidative conditions such as inflammation and diabetes are the major determinants of FORT values in patients with AMI.

Prognostic value of N-terminal pro-brain natriuretic peptide in elderly people with acute myocardial infarction: prospective observational study.

OBJECTIVE: To examine the influence of age on the predictive value of N-terminal pro-brain natriuretic (NT-proBNP) peptide assay in acute myocardial infarction. DESIGN: Prospective observational study. SETTING: All intensive care units in one French region. PARTICIPANTS: 3291 consecutive patients admitted for an acute myocardial infarction, from the RICO survey (a French regional survey for acute myocardial infarction). MAIN OUTCOME MEASURE: Cardiovascular death at 1 year. RESULTS: Among the 3291 participants, mean age was 68 (SD 14) years and 2356 (72%) were men. In the study population, the median NT-proBNP concentration was 1053 (interquartile range 300-3472) pg/ml. Median values for age quarters 1 to 4 were 367 (119-1050), 696 (201-1950), 1536 (534-4146), and 3774 (1168-9724) pg/ml (P<0.001). A multiple linear regression analysis was done to determine the factors associated with the pro-peptide concentrations in the overall population. NT-proBNP was mainly associated with age, left ventricular ejection fraction, creatinine clearance, female sex, hypertension, diabetes, and anterior wall infarction. At one year's follow-up, 384 (12%) patients had died from all causes and 372 (11%) from cardiovascular causes. In multivariate analysis, NT-proBNP remained strongly associated with the outcome, beyond traditional risk factors including creatinine clearance and left ventricular ejection fraction, in each age group except in the youngest one (<54 years) (P=0.29). The addition of NT-proBNP significantly improved the performance of the statistical model in the overall study population (-2log likelihood 3179.58 v 3099.74, P<0.001) and in each age quarter including the upper one (1523.52 v 1495.01, P<0.001).The independent discriminative value of NT-proBNP compared with the GRACE score was tested by a diagonal stratification using the median value of the GRACE score and NT-proBNP in older patients (upper quarter). Such stratification strikingly identified a high risk group-patients from the higher NT-proBNP group and with a high risk score-characterised by a risk of death of almost 50% at one year. CONCLUSIONS: In this large contemporary non-selected cohort of patients with myocardial infarction, NT-proBNP concentration had incremental prognostic value even in the oldest patients, above and beyond the GRACE risk score and traditional biomarkers after acute myocardial infarction. These data further support the potential interest of clinical trials specifically assessing NT-proBNP measurement as a guide to current treatment strategies, as well as novel strategies, in older patients with acute myocardial infarction.

Antioxidant properties of alpha-lipoic acid: effects on red blood membrane permeability and adaptation of isolated rat heart to reversible ischemia.

The aim of our work was to study (1) the antioxidant properties of lipoic acid (LA) and its reduced metabolite dihydrolipoic acid (DHLA) formed by reduction of LA and (2) the effects of treatment with LA and DHLA on (a) K(+) efflux from human red blood cells and (b) post-ischemic recovery and oxidative stress in isolated perfused rat hearts challenged with an ischemia-reperfusion (IR) sequence. In vitro, we used xanthine and xanthine oxidase to generate superoxide anion, which is not directly measurable by electron paramagnetic resonance (EPR), but specifically oxidizes the spin probe CPH into an EPR-detectable long lasting CP(*) nitroxide radical. While 5 mM of LA was ineffective in reducing the kinetics of CP(*) nitroxide formation, DHLA was shown to lessen this rate in a dose-dependent manner and at 30 mM was even more efficient than 300 UI/ml SOD. These results are in agreement with the fact that DHLA is able to directly scavenge superoxide anion. Red cells are a good model to investigate oxidative damage in biological membranes; hence, we used a suspension of erythrocytes incubated with 2,2(')-azobis(2-amidinopropane) hydrochloride (AAPH) which generates in vitro free radicals. DHLA provided more effective protection of red cells membranes than LA; DHLA was comparable to Trolox for its antioxidant potency. In vivo, treatment of rats (50 mg/kg/day i.p. for 7 days) with LA induced a slight increase in coronary flow (CF) in isolated perfused hearts, after 30 min of global total ischemia. This effect was not associated with an improvement in contractile function and reduction of myocardial oxidative stress. In conclusion, because of their ability to scavenge free radicals, LA and to an even greater degree DHLA were able to protect the membranes of red blood cells. This finding suggests that LA and DHLA might be useful in the treatment of diseases associated with oxidative stress such as diabetes.

[Epidemiology of acute coronary syndrome in Europe]. / Epidémiologie du syndrome coronaire aigu en Europe.

Epidemiological data concerning acute coronary syndromes in Europe are based on national registries, studies by the European Society of Cardiology within the framework of the EuroHeart Survey and on the study of European population sub-groups in large international cohorts. In this article, recently published studies will be reviewed, and the principal developments in different countries as well as the characteristics and particularities of the most recent epidemiological data will be highlighted. In Europe, the presentation of acute coronary syndromes (ACS) has evolved considerably over the last ten years. This evolution is characterized by a reduction in the proportion of acute coronary syndromes with ST-segment elevation (STEMI) and by ageing populations.

Influence of rosuvastatin on the NAD(P)H oxidase activity in the retina and electroretinographic response of spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: Retinal complications may be encountered during the development of hypertension as a response to oxidative stress. Statins may reduce the risk of developing hypertension and ocular diseases. We evaluate the effects of rosuvastatin (ROSU) on retinal functionality and oxidative stress levels in normotensive and spontaneously hypertensive rats (SHR). EXPERIMENTAL APPROACH: Wistar Kyoto (WKY) and SHR were treated for 3 weeks with rosuvastatin (10 mg kg(-1) day(-1)). Electroretinograms (ERG) were recorded before and after rosuvastatin treatment. Reactive oxygen species (ROS) were determined in the retina with dihydroethidium staining and NAD(P)H oxidase activity was evaluated. KEY RESULTS: Retinal ganglion cell ROS and retinal NAD(P)H oxidase activity were higher in SHR than in WKY rats, respectively (17.1+/-1.1 vs 10.2+/-1.2 AU, P<0.01; 38095+/-8900 vs 14081+/-5820 RLU mg(-1); P<0.05). The ERG b-wave amplitude in SHR was significantly lower than that in WKY rats. Rosuvastatin reduced SBP in SHR but did not change plasma lipid levels. Rosuvastatin treatment in SHR significantly decreased ROS levels (11.2+/-1.3, P<0.01), NAD(P)H activity in retinal ganglion cells (9889+/-4290; P<0.05), and increased retinal plasmalogen content in SHR, but did not modify the ERG response. CONCLUSIONS AND IMPLICATIONS: Rosuvastatin, beyond lowering cholesterol levels, was able to lower ROS in the retina induced by hypertension, but without improving retinal function in SHR. These findings point to a complex relationship between ROS in the pathogenesis of retinal disease and hypertension.

High levels of N-terminal pro B-type natriuretic peptide are associated with ST resolution failure after reperfusion for acute myocardial infarction.

BACKGROUND: B-type natriuretic peptide and the N-terminal fragment of its prohormone, N-terminal pro-brain natriuretic peptide (Nt-proBNP), provide valuable prognostic information on short- and long-term mortality in patients with acute coronary syndrome AIM: To investigate the association between plasma NT-proBNP levels and ST-segment resolution (STR) after reperfusion in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Consecutive patients from the French regional RICO survey with STEMI who were treated by primary PCI or lysis <12 h were included. Blood sample was taken on admission to measure plasma NT-proBNP. Maximal ST segment elevation was measured on the single worst ECG lead before and 90 min after reperfusion. Patients were categorized as STR(-) (<50% STR) or STR(+) (>or=50% STR). RESULTS: Of the 486 patients included, 133 (27%) were STR(-). STR(-) patients had similar cardiovascular risk factors but higher in-hospital mortality (5% vs. 1%, p=0.03) than STR(+) patients. The STR(-) group had higher median (IQR) levels of Nt-proBNP: 938 (211-3272) vs. 533 (169-1471) pg/ml, p=0.003. On multivariate analysis, the highest quartile of Nt-ProBNP, Q waves and lysis were independent risk factors for incomplete STR. DISCUSSION: Our data show a strong association between high levels of Nt-proBNP at admission and incomplete STR, suggesting that Nt-proBNP may be useful for early risk stratification in reperfusion therapy after acute myocardial infarction.

Impact of chronic oral anticoagulation on management and outcomes of patients with acute myocardial infarction: data from the RICO survey.

OBJECTIVE: To determine the prevalence of chronic oral anticoagulant drug treatment (COA) among patients with acute myocardial infarction (AMI) and its impact on management and outcome. METHODS: All patients with ST segment elevation AMI on the RICO (a French regional survey for AMI) database were included in this analysis. COA was defined as continuous use >or= 48 hours before AMI. RESULTS: Among the 2112 patients with ST elevation myocardial infarction (STEMI), 93 (4%) patients were receiving COA. These patients were older and more likely to have a history of hypertension, diabetes and prior myocardial infarction than patients without COA. In addition, fewer patients who received COA underwent reperfusion therapy or received an antiplatelet agent (aspirin/thienopyridines). Moreover, patients receiving COA experienced a higher incidence of in-hospital major adverse events (death, recurrent myocardial infarction or major bleeding, p = 0.005). Multivariate analysis showed that only ejection fraction, current smoking and multiple vessel disease, but not COA, were independent predictive factors for major adverse events. In contrast, COA was an independent predictive factor for heart failure when adjusted for age, diabetes, creatinine clearance, reperfusion, heparin and glycoprotein IIb/IIIa inhibitors (odds ratio 2.06, CI 95% 1.23 to 3.43, p = 0.005). CONCLUSION: In this population based registry, patients with STEMI with prior use of COA constituted a fairly large group (4%) with an overall higher baseline risk profile than that of patients without COA. Fewer in the COA group received reperfusion therapy or aggressive antithrombotic treatment and they experienced more adverse in-hospital outcomes. Thus, further studies are warranted to develop specific management strategies for this high risk group.

[A treatment with rosuvastatin induced a reduction of arterial pressure and a decrease of oxidative stress in spontaneously hypertensive rats]. / Un traitement par la rosuvastatine induit une réduction de la pression artérielle et une diminution du niveau du stress oxydatif chez le rat spontanément hypertendu.

The aim of this study was to appreciate consequences of rosuvastatin administration on hemodynamic function, vascular oxidative stress and ischemia/reperfusion disorders in normotensive and hypertensive rats. At 10 weeks of age, spontaneously hypertensive rats (SHR, n=20) and normotensive Wistar Kyoto male rats (WKY, n=20) were divided into four groups and given, either vehicle or 10 mg/kg/day of rosuvastatin by gavage for 3 weeks. Systolic blood pressure was assessed every week. At the end of these treatments, vascular NADPH oxidase activity was evaluated by chemiluminescence (lucigenin 0.5 microM). Hearts were isolated and perfused according to the Langendorff method and were subjected to 30 min of global ischemia. Reactive oxygen species (ROS) produced during reperfusion were quantified by electron spin resonance (ESR) spectroscopy using a spin probe (CP-H, 1 mM). After one week of treatment, rosuvastatin reduced the arterial pressure in SHR rats (180.3 +/- 2.1, SHR vs 169.7 +/- 2.3 mmHg, SHR+rosuvastatin; p < 0.01), without lowering plasma cholesterol levels; these effects were not observed in WKY. NADPH activity was 25% higher in control SHR rat aortas compared to control WKY, and was reduced by rosuvastatin in SHR rats. In isolated rat hearts subjected to ischemia/reperfusion sequences, there was a deterioration in functional parameters in control SHR compared to control WKY hearts. Rosuvastatin decreased post-ischemic contracture in WKY hearts by 50% (41.5 +/- 7.5, WKY control vs 18.4 +/- 4.6 mmHg, WKY+rosuvastatin; p < 0.01) and increased left ventricular developed pressure. This beneficial effect was accompanied by a decrease in ROS detected by ESR during reperfusion (312.5 +/- 45.3, WKY control; vs 219.3 +/- 22.9 AUC/mL, WKY+rosuvastatin; p < 0.05). In conclusion, these results are in accordance with the hypothesis that oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases including hypertension, and demonstrate the beneficial effects of rosuvastatin.

Cyclomaltodextrin glucanotransferase from Bacillus circulans E 192: nitration with tetranitromethane.

Nitration of tyrosine residues was performed on Bacillus circulans E 192 cyclomaltodextrin glucanotransferase (CGTase) using tetranitromethane (TNM). A maximum of 15 out of 28 tyrosine residues is modified with 8 mM TNM, entailing a concomitant loss of enzymic activity and tryptophan fluorescence. Spectroscopic studies suggest that these two phenomena are related to an impairment of the enzyme conformation as a consequence of the tyrosine nitration. The presence of 5 mM acarbose during the CGTase nitration results in the protection of one tyrosine residue and the rate of inactivation is reduced 9.4-fold. These results support a contribution of a tyrosine residue in the CGTase catalytic site. The nitration of CGTase also entails a decrease in the enzyme's affinity for a beta-cyclodextrin (beta-CD) co-polymer. Kinetic and analytical investigations on isolated modified enzymes support the concept that this phenomenon is unrelated to the modification of tyrosine residues, but rather concerns a side reaction of the reagent occurring at the raw-starch-binding site of the CGTase.

Cyclomaltodextrin glucanotransferase from Bacillus circulans E 192. I. Purification and characterization of the enzyme.

The cyclomaltrodextrin glucanotransferase (CGTase) [1,4-alpha-D-glucan:4-alpha-D-(1,4-alpha-D-glucano)-transferase (cyclizing), EC 2.4.1.19] from Bacillus circulans E 192 has been purified to homogeneity by Cetavlon treatment, ammonium sulfate precipitation, DEAE Trisacryl M chromatography, Q Fast Flow chromatography, and affinity on beta-cyclodextrin-Sepharose 4B. Two isoenzymes were separated by FPLC on a Mono Q column. Their isoelectric points were estimated as 6.7 and 6.9 and they represented 13 and 87%, respectively, of the initial activity. Their molecular weight, pH, and temperature optima were estimated as 78,000, 5.5, and 60 degrees C, respectively. Kinetic parameters indicated that both enzymes had the same properties; they preferentially modified high-molecular-weight substrates to produce cyclodextrins. The apparent Vmax and Km values for soluble starch were 43 mumol of beta-cyclodextrin/min/mg of protein and 0.57% (w/v), respectively. Although this CGTase is not markedly thermostable, it is protected against heat denaturation by substrate, product, and/or calcium ions. The ratios of alpha-, beta-, and gamma-cyclodextrins produced have been determined as 1/7/2 in the initial phase of the reaction and 3/3/1 at equilibrium.