Impact of different exercise training modalities on the coronary collateral circulation and plaque composition in patients with significant coronary artery disease (EXCITE trial): study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Exercise training (ET) in addition to optimal medical therapy (OMT) in patients with stable coronary artery disease (CAD) has been demonstrated to be superior to percutaneous coronary interventions (PCI) with respect to the composite endpoint of death, myocardial infarction, stroke, revascularization and hospitalization due to worsening of angina. One mechanism leading to this superiority discussed in the literature is the increase in coronary collateral blood flow due to ET. Until now, data demonstrating the positive effect of ET on the collateral blood flow and the functional capacity of the coronary collateral circulation are still lacking.Methods/designThe EXCITE trial is a three-armed randomized, prospective, single-center, open-label, controlled study enrolling 60 patients with stable CAD and at least one significant coronary stenosis (fractional flow reserve <=0.75). The study is designed to compare the influence and efficacy of two different 4-week ET programs [high-intensity interval trainings (IT) versus moderate-intensity exercise training (MT) in addition to OMT] versus OMT only on collateral blood flow (CBF). The primary efficacy endpoint is the change of the CBF of the target vessel after 4 weeks as assessed by coronary catheterization with a pressure wire during interruption of the antegrade flow of the target vessel by balloon occlusion. Secondary endpoints include the change in plaque composition as assessed by intravascular ultrasound (IVUS) after 4 weeks, myocardial perfusion as analyzed in MRI after 4 weeks and 12 months, peak oxygen uptake (V02 peak), change in endothelial function and biomarkers after 4 weeks, 3, 6 and 12 months. The safety endpoint addresses major adverse cardiovascular events (death from cardiovascular cause, myocardial infarction, stroke, TIA, target vessel revascularization or hospitalization) after 12 months. DISCUSSION: The trial investigates whether ET for 4 weeks increases the CBF in patients with significant CAD compared to a sedentary control group. It also examines the impact of two intensities of ET on the CBF as well as the histological plaque composition. The trial started recruitment in June 2009 and will complete recruitment until June 2012. First results are expected in December 2012 (4-week follow-up), final results (12-month long-term secondary endpoint) in December 2013.Trial registrationClinical trial registration information-URL: www.clinicaltrials.gov.Unique identifier: NCT01209637.     

Vibrational spectroscopic studies to acquire a quality control method of Eucalyptus essential oils

This article presents a novel and original approach to analyze in situ the main components of Eucalyptus oil by means of Raman spectroscopy. The obtained two-dimensional Raman maps demonstrate a unique possibility to study the essential oil distribution in the intact plant tissue. Additionally, Fourier Transform (FT)-Raman and attenuated total reflection (ATR)-IR spectra of essential oils isolated from several Eucalyptus species by hydrodistillation are presented. Density Functional Theory (DFT) calculations were performed in order to interpret the spectra of the essential oils of the Eucalyptus species. It is shown that the main components of the essential oils can be recognized by both vibrational spectroscopic techniques using the spectral information of the pure terpenoids. Spectroscopic analysis is based on the key bands of the individual volatile substances and therefore allows one to discriminate different essential oil profiles of several Eucalyptus species. It has been found that the presented spectroscopic data correlate very well with those obtained by gas chromatography (GC) analysis. All these investigations are helpful tools to generate a fast and easy method to control the quality of the essential oils with vibrational spectroscopic techniques in combination with DFT calculations.     

Eigenschaften von Nervenimpulsfolgen

Summary In the first part of this paper some phenomena in the nervous system are described, concerning the time interval structure of the nervous signals. The characteristics of the neurons are introduced and interpreted. It is shown theoretically and proved by experiments, that the time interval distributions in the axons can be appoximated by gamma-distributions.In the second part, some experiments with electronic neuron models are described. It is tried to find a correlation between the interval distributions of the output signals and the structure of the systems.The third part concerns experiments at the cerci of the cockroach periplaneta americana. From the measured transition probabilities for various amplitudes, the entropy, the transinformation rate and the channel capacity of various nervous channels are calculated.The average transinformation rate results between 1.5 to 30 bit/sec. The channel capacity is about threefold the transinformation rate.

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Die Autoren danken Herrn Professor Dr.-Ing. habil. H. Tischner für die Anregung zu dieser Arbeit und der Deutschen Forschungsgemeinschaft für die Bereitstellung der notwendigen Mittel.     

Age‐depending effects of narcosis and transmitter implantation on circadian body temperature and activity rhythms in mice

Summary

The effects of narcosis and of telemetry transmitter implantation on core temperature and locomotor activity were investigated in female laboratory mice of various age (3, 15 and 52 weeks old). Following surgery a transient hypothermia was observed. The body temperatures measured 30 min after beginning of narcosis were lower in juvenile and in presenile mice (29.6° ±0.8°C resp. 30.0° ±0.2°C) than in adult animals (31.9° ±0.3°C). The following temperature increase was fastest in juvenile mice. Normal body temperature was reached after 6h 20’ already. Adult and presenile mice needed 8h 30’ resp. 7h 30’. The temperature increase seemed to be independent from activity behaviour of the animals. No substantial differences could be obtained whether the transmitters had room or body temperature before implantation and whether the animals were warmed after surgery by an infrared bulb or not. Probably, the temperature increase depended mainly on the elimination rate of the drug.

Normal circadian core temperature and activity rhythms reappeared on average within 5–6 days in juvenile mice and a little faster in adult (4–5 days) as well as in presenile ones (3–4 days). However, interindividual differences in recovery time were more pronounced than age‐dependent variations.

Circadian core temperature and activity patterns were quite similar in all three age classes investigated. Ontogenetic differences concern, besides changes in daily mean values, mainly a temperature amplitude increasing with age, as well as a high percentage of ultradian components in the activity pattern of juvenile mice compared to older ones.

Telemetry systems are widely used for long‐term measurements of core temperature in laboratory animals (Clement et al., 1989; Refinetti and Menaker, 1992). In our investigations of ontogenetic changes of the circadian temperature and activity rhythms in mice we used an integrated telemetry and data acquisition system (Dataquest, Data Sciences Inc., USA). It comprises implantable wireless transmitters, telemetry receivers, a consolidation matrix and a data acquisition system. The aim of a preliminary study was to analyse the effects of narcosis and transmitter implantation. The time required to recover normal values of body temperature and of locomotor activity as well as normal circadian rhythms was determined, considering also ontogenetic variations.     

Gαq allosterically activates and relieves autoinhibition of p63RhoGEF

Gα_q directly activates p63RhoGEF and closely related catalytic domains found in Trio and Kalirin, thereby linking G_q-coupled receptors to the activation of RhoA. Although the crystal structure of Gα_q in complex with the catalytic domains of p63RhoGEF is available, the molecular mechanism of activation has not yet been defined. In this study, we show that membrane translocation does not appear to play a role in Gα_q-mediated activation of p63RhoGEF, as it does in some other RhoGEFs. Gα_q instead must act allosterically. We next identify specific structural elements in the PH domain that inhibit basal nucleotide exchange activity, and provide evidence that Gα_q overcomes this inhibition by altering the conformation of the α6–αN linker that joins the DH and PH domains, a region that forms direct contacts with RhoA. We also identify residues in Gα_q that are important for the activation of p63RhoGEF and that contribute to Gα subfamily selectivity, including a critical residue in the Gα_q C-terminal helix, and demonstrate the importance of these residues for RhoA activation in living cells.     

Urinary Pyrophosphate in Normal Subjects and in Stone Formers

The urinary excretion of inorganic pyrophosphate was determined in nine normal subjects and also in eight patients with recurrent calcium-containing renal stones during varied levels of phosphate intake. The excretion of pyrophosphate and orthophosphate is virtually the same in the two groups at all levels of phosphate intake. It appears unlikely that a consistently reduced urinary excretion of pyrophosphate is a factor in the formation of urinary calculi. Pyrophosphate excretion rose and calcium excretion fell with increasing phosphate intake; this might be expected to have a beneficial effect in patients with recurrent calcium stones.     

Conjugation dynamics depend on both the plasmid acquisition cost and the fitness cost

Plasmid conjugation is a major mechanism responsible for the spread of antibiotic resistance. Plasmid fitness costs are known to impact long‐term growth dynamics of microbial populations by providing plasmid‐carrying cells a relative (dis)advantage compared to plasmid‐free counterparts. Separately, plasmid acquisition introduces an immediate, but transient, metabolic perturbation. However, the impact of these short‐term effects on subsequent growth dynamics has not previously been established. Here, we observed that de novo transconjugants grew significantly slower and/or with overall prolonged lag times, compared to lineages that had been replicating for several generations, indicating the presence of a plasmid acquisition cost. These effects were general to diverse incompatibility groups, well‐characterized and clinically captured plasmids, Gram‐negative recipient strains and species, and experimental conditions. Modeling revealed that both fitness and acquisition costs modulate overall conjugation dynamics, validated with previously published data. These results suggest that the hours immediately following conjugation may play a critical role in both short‐ and long‐term plasmid prevalence. This time frame is particularly relevant to microbiomes with high plasmid/strain diversity considered to be hot spots for conjugation.     

Antibody-based tissue profiling as a tool for clinical proteomics

Here, we show a strategy for high-throughput antibody-based tissue profiling with the aim to create an atlas of protein expression patterns in normal human tissues and cancer tissues representing the 20 most prevalent cancer types. A set of standardized tissue microarrays (TMAs) was produced to allow for rapid screening of a multitude of different cells and tissues using immunohistochemistry. Eight TMA blocks were produced containing 48 different normal human tissues in triplicate and cancer tissue from 216 individually different tumors in duplicate. Sections from these blocks were immunohistochemically stained using five commercial and five in-house generated antibodies. Digital images for annotation of expression profiles were generated using a semiautomated approach. Five hundred seventy-six images and annotation data corresponding to a total of 30 Gbytes of data were collected for each antibody. The data presented here suggest that antibody-based profiling of protein expression in tissues can be used as a valuable tool in clinical proteomics.