Field-Dependent Reduced Ion Mobilities of Positive and Negative Ions in Air and Nitrogen in High Kinetic Energy Ion Mobility Spectrometry (HiKE-IMS)

In High Kinetic Energy Ion Mobility Spectrometry (HiKE-IMS), ions are formed in a reaction region and separated in a drift region, which is similar to classical drift tube ion mobility spectrometers (IMS) operated at ambient pressure. However, in contrast to the latter, the HiKE-IMS is operated at a decreased background pressure of 10–40 mbar and achieves high reduced electric field strengths of up to 120 Td in both the reaction and the drift region. Thus, the HiKE-IMS allows insights into the chemical kinetics of ion-bound water cluster systems at effective ion temperatures exceeding 1000 K, although it is operated at the low absolute temperature of 45 °C. In this work, a HiKE-IMS with a high resolving power of RP = 140 is used to study the dependence of reduced ion mobilities on the drift gas humidity and the effective ion temperature for the positive reactant ions H3O+(H2O)n, O2+(H2O)n, NO+(H2O)n, NO2+(H2O)n, and NH4+(H2O)n, as well as the negative reactant ions O2–(H2O)n, O3–(H2O)n, CO3–(H2O)n, HCO3–(H2O)n, and NO2–(H2O)n. By varying the reduced electric field strength in the drift region, cluster transitions are observed in the ion mobility spectra. This is demonstrated for the cluster systems H3O+(H2O)n and NO+(H2O)n

Negative Reactant Ion Formation in High Kinetic Energy Ion Mobility Spectrometry (HiKE-IMS)

Due to the operation at background pressures between 10-40 mbar and high reduced electric field strengths of up to 120 Td, the ion–molecule reactions in High Kinetic Energy Ion Mobility Spectrometers (HiKE-IMS) differ from those in classical ambient pressure IMS. In the positive ion polarity mode, the reactant ions H+(H2O)n, O2+(H2O)n, and NO+(H2O)n are observed in the HiKE-IMS. The relative abundances of these reactant ion species significantly depend on the reduced electric field strength in the reaction region, the operating pressure, and the water concentration in the reaction region. In this work, the formation of negative reactant ions in HiKE-IMS is investigated in detail. On the basis of kinetic and thermodynamic data from the literature, the processes resulting in the formation of negative reactant ions are kinetically modeled. To verify the model, we present measurements of the negative reactant ion population in the HiKE-IMS and its dependence on the reduced electric field strength as well as the water and carbon dioxide concentrations in the reaction region. The ion species underlying individual peaks in the ion mobility spectrum are identified by coupling the HiKE-IMS to a time-of-flight mass spectrometer (TOF-MS) using a simple gated interface that enables the transfer of selected peaks of the ion mobility spectrum into the TOF-MS. Both the theoretical model as well as the experimental data suggest the predominant generation of the oxygen-based ions O–, OH–, O2–, and O3– in purified air containing 70 ppmv of water and 30 ppmv of carbon dioxide. Additionally, small amounts of NO2– and CO3– are observed. Their relative abundances highly depend on the reduced electric field strength as well as the water and carbon dioxide concentration. An increase of the water concentration in the reaction region results in the generation of OH– ions, whereas increasing the carbon dioxide concentration favors the generation of CO3– ions, as expected

Positive Reactant Ion Formation in High Kinetic Energy Ion Mobility Spectrometry (HiKE-IMS)

In contrast to classical Ion Mobility Spectrometers (IMS) operating at ambient pressure, the High Kinetic Energy Ion Mobility Spectrometer (HiKE-IMS) is operated at reduced pressures of between 10 and 40 mbar and higher reduced electric field strengths of up to 120 Td. Thus, the ion–molecule reactions occurring in the HiKE-IMS can significantly differ from those in classical ambient pressure IMS. In order to predict the ionization pathways of specific analyte molecules, profound knowledge of the reactant ion species generated in HiKE-IMS and their dependence on the ionization conditions is essential. In this work, the formation of positive reactant ions in HiKE-IMS is investigated in detail. On the basis of kinetic and thermodynamic data from the literature, the ion–molecule reactions are kinetically modeled. To verify the model, we present measurements of the reactant ion population and its dependence on the reduced electric field strength, the operating pressure, and the water concentration in the sample gas. All of these parameters significantly affect the reactant ion population formed in HiKE-IMS

Raltitrexed (Tomudex): an alternative drug for patients with colorectal cancer and 5-fluorouracil associated cardiotoxicity.

Two patients with proven 5-fluorouracil (5-FU)-associated cardiotoxicity were treated with the specific thymidylate synthase inhibitor raltitrexed safely, without evidence of cardiotoxicity. Raltitrexed might be an alternative for patients with advanced colorectal cancer and 5-FU-associated cardiotoxicity. 5-FU cardiotoxicity is not due to the antineoplastic mechanisms via thymidilate synthase

Plasma exchange for primary autoimmune autonomic failure

We report on a patient with long-standing severe autonomic failure that affected his sympathetic and parasympathetic nervous systems. Antibodies against the ganglionic acetylcholine receptors were detected in the serum. Removal of the antibodies by means of plasma exchange resulted in a dramatic clinical improvement

ACE2-Mediated Reduction of Oxidative Stress in the Central Nervous System Is Associated with Improvement of Autonomic Function

Oxidative stress in the central nervous system mediates the increase in sympathetic tone that precedes the development of hypertension. We hypothesized that by transforming Angiotensin-II (AngII) into Ang-(1–7), ACE2 might reduce AngII-mediated oxidative stress in the brain and prevent autonomic dysfunction. To test this hypothesis, a relationship between ACE2 and oxidative stress was first confirmed in a mouse neuroblastoma cell line (Neuro2A cells) treated with AngII and infected with Ad-hACE2. ACE2 overexpression resulted in a reduction of reactive oxygen species (ROS) formation. In vivo, ACE2 knockout (ACE2−/y) mice and non-transgenic (NT) littermates were infused with AngII (10 days) and infected with Ad-hACE2 in the paraventricular nucleus (PVN). Baseline blood pressure (BP), AngII and brain ROS levels were not different between young mice (12 weeks). However, cardiac sympathetic tone, brain NADPH oxidase and SOD activities were significantly increased in ACE2−/y. Post infusion, plasma and brain AngII levels were also significantly higher in ACE2−/y, although BP was similarly increased in both genotypes. ROS formation in the PVN and RVLM was significantly higher in ACE2−/y mice following AngII infusion. Similar phenotypes, i.e. increased oxidative stress, exacerbated dysautonomia and hypertension, were also observed on baseline in mature ACE2−/y mice (48 weeks). ACE2 gene therapy to the PVN reduced AngII-mediated increase in NADPH oxidase activity and normalized cardiac dysautonomia in ACE2−/y mice. Altogether, these data indicate that ACE2 gene deletion promotes age-dependent oxidative stress, autonomic dysfunction and hypertension, while PVN-targeted ACE2 gene therapy decreases ROS formation via NADPH oxidase inhibition and improves autonomic function. Accordingly, ACE2 could represent a new target for the treatment of hypertension-associated dysautonomia and oxidative stress

Elevation of the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline: a blood pressure-independent beneficial effect of angiotensin I-converting enzyme inhibitors

Blockade of the renin-angiotensin system (RAS) is well recognized as an essential therapy in hypertensive, heart, and kidney diseases. There are several classes of drugs that block the RAS; these drugs are known to exhibit antifibrotic action. An analysis of the molecular mechanisms of action for these drugs can reveal potential differences in their antifibrotic roles. In this review, we discuss the antifibrotic action of RAS blockade with an emphasis on the potential importance of angiotensin I-converting enzyme (ACE) inhibition associated with the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP)