Ramipril increases the protein level of skeletal muscle IRS-1 and alters protein tyrosine phosphatase activity in spontaneously hypertensive rats

To investigate mechanisms by which angiotensin converting enzyme (ACE)-inhibition increases insulin sensitivity, spontaneously hypertensive (SH) rats were treated with or without ramipril (1 mg/kg per day) for 12 weeks. Insulin binding and protein levels of insulin receptor substrate-1 (IRS-1), p85-subunit of phosphatidylinositol 3'-kinase (p85) and Src homology 2 domain-containing phosphatase-2 (SHP2) were then determined in hindlimb muscle and liver. Additionally, protein tyrosine phosphatase (PTPase) activities towards immobilized phosphorylated insulin receptor or phosphorylated IRS-1 of membrane (MF) and cytosolic fractions (CF) of these tissues were measured. Ramipril treatment increased IRS-1-protein content in muscle by 31+/-9% (P<0.05). No effects were observed on IRS-1 content in liver or on insulin binding or protein expression of p85 or SHP2 in both tissues. Ramipril treatment also increased dephosphorylation of insulin receptor by muscle CF (22.0+/-1.0%/60 min compared to 16.8+/-1.5%/60 min; P<0.05), and of IRS-1 by liver MF (37.2+/-1.7%/7.5 min compared to 33.8+/-1.7%/7.5 min; P<0.05) and CF (36.8+/-1.0%/7.5 min compared to 33.2+/-1.0%/7.5 min; P<0.05). We conclude that the observed effects of ACE-inhibition by ramipril on the protein expression of IRS-1 and on PTPase activity might contribute to its effect on insulin sensitivity.

Endogenous angiotensinergic system in neurons of rat and human trigeminal ganglia

To clarify the role of Angiotensin II (Ang II) in the sensory system and especially in the trigeminal ganglia, we studied the expression of angiotensinogen (Ang-N)-, renin-, angiotensin converting enzyme (ACE)- and cathepsin D-mRNA, and the presence of Ang II and substance P in the rat and human trigeminal ganglia. The rat trigeminal ganglia expressed substantial amounts of Ang-N- and ACE mRNA as determined by quantitative real time PCR. Renin mRNA was untraceable in rat samples. Cathepsin D was detected in the rat trigeminal ganglia indicating the possibility of existence of pathways alternative to renin for Ang I formation. In situ hybridization in rat trigeminal ganglia revealed expression of Ang-N mRNA in the cytoplasm of numerous neurons. By using immunocytochemistry, a number of neurons and their processes in both the rat and human trigeminal ganglia were stained for Ang II. Post in situ hybridization immunocytochemistry reveals that in the rat trigeminal ganglia some, but not all Ang-N mRNA-positive neurons marked for Ang II. In some neurons Substance P was found colocalized with Ang II. Angiotensins from rat trigeminal ganglia were quantitated by radioimmunoassay with and without prior separation by high performance liquid chromatography. Immunoreactive angiotensin II (ir-Ang II) was consistently present and the sum of true Ang II (1-8) octapeptide and its specifically measured metabolites were found to account for it. Radioimmunological and immunocytochemical evidence of ir-Ang II in neuronal tissue is compatible with Ang II as a neurotransmitter. In conclusion, these results suggest that Ang II could be produced locally in the neurons of rat trigeminal ganglia. The localization and colocalization of neuronal Ang II with Substance P in the trigeminal ganglia neurons may be the basis for a participation and function of Ang II in the regulation of nociception and migraine pathology.

[Abdominal aortic aneurysm]

Abdominal aortic aneurysms (AAA) confer a substantial healthcare burden in the Western world. Surgical or endovascular therapy is indicated in patients with a maximum diameter exceeding 5.5 cm. Patients with smaller AAA must undergo a specific ultrasound surveillance program aimed at avoiding exposure to an increased risk of rupture once their AAA exceeds the threshold for active treatment. Based on improved understanding of the pathophysiology of AAA, recent years provided initial insight into potential medical treatment options. The presence of AAA is currently regarded a coronary artery disease risk equivalent. ACE inhibitors, statins and JNK-inhibitors were shown to have the potential to slow down progression. Since cigarette smoking is the main risk factor for both the development and progression of AAA, smoking cessation remains a key goal. Further prospective studies will assess the clinical efficacy of various promising drug treatment approaches aimed at slowing disease progression of small AAA and after endovascular therapy.

Validation of water vapour profiles (version 13) retrieved by the IMK / IAA scientific retrieval processor based on full resolution spectra measured by MIPAS on board Envisat

Vertical profiles of stratospheric water vapour measured by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) with the full resolution mode between September 2002 and March 2004 and retrieved with the IMK/IAA scientific retrieval processor were compared to a number of independent measurements in order to estimate the bias and to validate the existing precision estimates of the MIPAS data. The estimated precision for MIPAS is 5 to 10% in the stratosphere, depending on altitude, latitude, and season. The independent instruments were: the Halogen Occultation Experiment (HALOE), the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS), the Improved Limb Atmospheric Spectrometer-II (ILAS-II), the Polar Ozone and Aerosol Measurement (POAM III) instrument, the Middle Atmospheric Water Vapour Radiometer (MIAWARA), the Michelson Interferometer for Passive Atmospheric Sounding, balloon-borne version (MIPAS-B), the Airborne Microwave Stratospheric Observing System (AMSOS), the Fluorescent Stratospheric Hygrometer for Balloon (FLASH-B), the NOAA frostpoint hygrometer, and the Fast In Situ Hygrometer (FISH). For the in-situ measurements and the ground based, air- and balloon borne remote sensing instruments, the measurements are restricted to central and northern Europe. The comparisons to satellite-borne instruments are predominantly at mid- to high latitudes on both hemispheres. In the stratosphere there is no clear indication of a bias in MIPAS data, because the independent measurements in some cases are drier and in some cases are moister than the MIPAS measurements. Compared to the infrared measurements of MIPAS, measurements in the ultraviolet and visible have a tendency to be high, whereas microwave measurements have a tendency to be low. The results of χ2-based precision validation are somewhat controversial among the comparison estimates. However, for comparison instruments whose error budget also includes errors due to uncertainties in spectrally interfering species and where good coincidences were found, the χ2 values found are in the expected range or even below. This suggests that there is no evidence of systematically underestimated MIPAS random errors.

The free escape continuum of diffuse ions upstream of the Earth's quasi-parallel bow shock

The Earth's bow shock is very efficient in accelerating ions out of the incident solar wind distribution to high energies (≈ 200 keV/e). Fluxes of energetic ions accelerated at the quasi-parallel bow shock, also known as diffuse ions, are best represented by exponential spectra in energy/charge, which require additional assumptions to be incorporated into these model spectra. One of these assumptions is a so-called "free escape boundary" along the interplanetary magnetic field into the upstream direction. Locations along the IBEX orbit are ideally suited for in situ measurements to investigate the existence of an upstream free escape boundary for bow shock accelerated ions. In this study we use 2 years of ion measurements from the background monitor on the IBEX spacecraft, supported by ACE solar wind observations. The IBEX Background Monitor is sensitive to protons > 14 keV, which includes the energy of the maximum flux for diffuse ions. With increasing distance from the bow shock along the interplanetary magnetic field, the count rates for diffuse ions stay constant for ions streaming away from the bow shock, while count rates for diffuse ions streaming toward the shock gradually decrease from a maximum value to ~1/e at distances of about 10 RE to 14 RE. These observations of a gradual decrease support the transition to a free escape continuum for ions of energy >14 keV at distances from 10 RE to 14 RE from the bow shock.

Validation of middle-atmospheric campaign-based water vapour measured by the ground-based microwave radiometer MIAWARA-C

Middle atmospheric water vapour can be used as a tracer for dynamical processes. It is mainly measured by satellite instruments and ground-based microwave radiometers. Ground-based instruments capable of measuring middle-atmospheric water vapour are sparse but valuable as they complement satellite measurements, are relatively easy to maintain and have a long lifetime. MIAWARA-C is a ground-based microwave radiometer for middle-atmospheric water vapour designed for use on measurement campaigns for both atmospheric case studies and instrument intercomparisons. MIAWARA-C's retrieval version 1.1 (v1.1) is set up in a such way as to provide a consistent data set even if the instrument is operated from different locations on a campaign basis. The sensitive altitude range for v1.1 extends from 4 hPa (37 km) to 0.017 hPa (75 km). For v1.1 the estimated systematic error is approximately 10% for all altitudes. At lower altitudes it is dominated by uncertainties in the calibration, with altitude the influence of spectroscopic and temperature uncertainties increases. The estimated random error increases with altitude from 5 to 25%. MIAWARA-C measures two polarisations of the incident radiation in separate receiver channels, and can therefore provide two measurements of the same air mass with independent instrumental noise. The standard deviation of the difference between the profiles obtained from the two polarisations is in excellent agreement with the estimated random measurement error of v1.1. In this paper, the quality of v1.1 data is assessed for measurements obtained at two different locations: (1) a total of 25 months of measurements in the Arctic (Sodankylä, 67.37° N, 26.63° E) and (2) nine months of measurements at mid-latitudes (Zimmerwald, 46.88° N, 7.46° E). For both locations MIAWARA-C's profiles are compared to measurements from the satellite experiments Aura MLS and MIPAS. In addition, comparisons to ACE-FTS and SOFIE are presented for the Arctic and to the ground-based radiometer MIAWARA for the mid-latitude campaigns. In general, all intercomparisons show high correlation coefficients, confirming the ability of MIAWARA-C to monitor temporal variations of the order of days. The biases are generally below 13% and within the estimated systematic uncertainty of MIAWARA-C. No consistent wet or dry bias is identified for MIAWARA-C. In addition, comparisons to the reference instruments indicate the estimated random error of v1.1 to be a realistic measure of the random variation on the retrieved profile between 45 and 70 km.

Intercomparison of stratospheric ozone profiles for the assessment of the upgraded GROMOS radiometer at Bern

Since November 1994, the GROund-based Millimeter-wave Ozone Spectrometer (GROMOS) measures stratospheric and lower mesospheric ozone in Bern, Switzerland (47.95° N, 7.44° E). GROMOS is part of the Network for the Detection of Atmospheric Composition Change (NDACC). In July 2009, a Fast-Fourier-Transform spectrometer (FFTS) has been added as backend to GROMOS. The new FFTS and the original filter bench (FB) measured parallel for over two years. In October 2011, the FB has been turned off and the FFTS is now used to continue the ozone time series. For a consolidated ozone time series in the frame of NDACC, the quality of the stratospheric ozone profiles obtained with the FFTS has to be assessed. The FFTS results from July 2009 to December 2011 are compared to ozone profiles retrieved by the FB. FFTS and FB of the GROMOS microwave radiometer agree within 5% above 20 hPa. A later harmonization of both time series will be realized by taking the FFTS as benchmark for the FB. Ozone profiles from the FFTS are also compared to coinciding lidar measurements from the Observatoire Haute Provence (OHP), France. For the time period studied a maximum mean difference (lidar – GROMOS FFTS) of +3.8% at 3.1 hPa and a minimum mean difference of +1.4% at 8 hPa is found. Further, intercomparisons with ozone profiles from other independent instruments are performed: satellite measurements include MIPAS onboard ENVISAT, SABER onboard TIMED, MLS onboard EOS Aura and ACE-FTS onboard SCISAT-1. Additionally, ozonesondes launched from Payerne, Switzerland, are used in the lower stratosphere. Mean relative differences of GROMOS FFTS and these independent instruments are less than 10% between 50 and 0.1 hPa.

Cardiac medication during pregnancy, data from the ROPAC

BACKGROUND Data on pharmacological management during pregnancy are scarce. The aim of this study was to describe the type and frequency of cardiac medication used in pregnancy in patients with cardiovascular disease and to assess the relationship between medication use and fetal outcome. METHODS AND RESULTS Between 2007 and 2011 sixty hospitals in 28 countries enrolled 1321 pregnant women. All patients had structural heart disease (congenital 66%, valvular 25% or cardiomyopathy 7% or ischemic 2%). Medication was used by 424 patients (32%) at some time during pregnancy: 22% used beta-blockers, 8% antiplatelet agents, 7% diuretics, 2.8% ACE inhibitors and 0.5% statins. Compared to those who did not take medication, patients taking medication were older, more likely to be parous, have valvular heart disease and were less often in sinus rhythm. The odds ratio of fetal adverse events in users versus non-users of medication was 2.6 (95% CI 2.0-3.4) and after adjustment for cardiac and obstetric parameter was 2.0 (95% CI 1.4-2.7). Babies of patients treated with beta-blockers had a significantly lower adjusted birth weight (3140 versus 3240 g, p = 0.002). The highest rate of fetal malformation was found in patients taking ACE inhibitors (8%). CONCLUSION One third of pregnant women with heart disease used cardiac medication during their pregnancy, which was associated with an increased rate of adverse fetal events. Birth weight was significantly lower in children of patients taking beta-blockers. A randomized trial is needed to distinguish the effects of the medication from the effects of the underlying maternal cardiac condition.

In situ plasma measurements of fragmented comet 73P Schwassmann–Wachmann 3

The interiors of comets contain some of the most pristine material in the solar system. Comet 73P/Schwassmann–Wachmann 3, discovered in 1930, is a Jupiter-family comet with a 5.34-year period. This comet split into 5 fragments in 1995 and disintegrated into nearly 70 major pieces in 2006. In 2006 May and June, recently ionized cometary particles originating from fragments including and surrounding some of these major objects were collected with the ACE/SWICS and Wind/STICS sensors. Due to a combination of the instrument characteristics and the close proximity of the fragments passing between those spacecraft and the Sun, unique measurements regarding the charge state composition and the elemental abundances of both cometary and heliospheric plasma were made during that time. The cometary material released from some of these fragments can be identified by the concentrations of water-group pickup ions having a mass-per-charge ratio of 16–18 amu e−1, indicating that while these fragments are small, they are still actively sublimating. We present an analysis of cometary composition, spatial distribution, and heliospheric interactions, with a focus on helium, C+/O+, and water-group ions.

Reasons for discontinuation of recommended therapies according to the patients after acute coronary syndromes.

BACKGROUND The prescription of recommended medical therapies is a key factor to improve prognosis after acute coronary syndromes (ACS). However, reasons for cardiovascular therapies discontinuation after hospital discharge are poorly reported in previous studies. METHODS We enrolled 3055 consecutive patients hospitalized with a main diagnosis of ACS in four Swiss university hospitals with a prospective one-year follow-up. We assessed the self-reported use of recommended therapies and the reasons for medication discontinuation according to the patient interview performed at one-year follow-up. RESULTS 3014 (99.3%) patients were discharged with aspirin, 2983 (98.4%) with statin, 2464 (81.2%) with beta-blocker, 2738 (90.3%) with ACE inhibitors/ARB and 2597 (100%) with P2Y12 inhibitors if treated with coronary stent. At the one-year follow-up, the discontinuation percentages were 2.9% for aspirin, 6.6% for statin, 11.6% for beta-blocker, 15.1% for ACE inhibitor/ARB and 17.8% for P2Y12 inhibitors. Most patients reported having discontinued their medication based on their physicians' decision: 64 (2.1%) for aspirin, 82 (2.7%) for statin, 212 (8.6%) for beta-blocker, 251 (9.1% for ACE inhibitor/ARB) and 293 (11.4%) for P2Y12 inhibitors, while side effect, perception that medication was unnecessary and medication costs were uncommon reported reasons (<2%) according to the patients. CONCLUSIONS Discontinuation of recommended therapies after ACS differs according the class of medication with the lowest percentages for aspirin. According to patients, most stopped their cardiovascular medication based on their physician's decision, while spontaneous discontinuation was infrequent.