It takes two peroxisome proliferator-activated receptors (PPAR-β/δ and PPAR-γ) to tango idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung epithelial phenotypes, fibroblast activation, and increased extracellular matrix deposition. Transforming growth factor-beta (TGF-β)1-induced Smad signaling and downregulation of peroxisomal genes are involved in the pathogenesis and can be inhibited by peroxisome proliferator-activated receptor (PPAR)-α activation. However, the three PPARs, that is PPAR-α, PPAR-β/δ, and PPAR-γ, are known to interact in a complex crosstalk.

Production of carbon-11 for PET preclinical imaging using a high-repetition rate laser-driven proton source.

Most advanced medical imaging techniques, such as positron-emission tomography (PET), require tracers that are produced in conventional particle accelerators. This paper focuses on the evaluation of a potential alternative technology based on laser-driven ion acceleration for the production of radioisotopes for PET imaging. We report for the first time the use of a high-repetition rate, ultra-intense laser system for the production of carbon-11 in multi-shot operation.

Fibroblast growth factor 10 reverses cigarette smoke- and elastase-induced emphysema and pulmonary hypertension in mice.

Background: COPD is an incurable disease and a leading cause of death worldwide. In mice, fibroblast growth factor (FGF)10 is essential for lung morphogenesis, and in humans, polymorphisms in the human gene correlate with an increased susceptibility to develop COPD.

Methods: We analysed FGF10 signalling in human lung sections and isolated cells from healthy donor, smoker and COPD lungs.

A Multicentre, Prospective, and Retrospective Registry to Characterize the Use, Effectiveness, and Safety of Dalbavancin in German Clinical Practice.

The antibiotic dalbavancin is approved for intravenous treatment of adults with acute bacterial skin and skin structure infections. This study aimed to observe the use, effectiveness, and safety of dalbavancin in clinical practice in Germany. It was a multicentre, prospective, and retrospective registry and consecutively enrolled patients treated with dalbavancin.

Excessive Accumulation of Intracellular Ca After Acute Exercise Potentiated Impairment of T-cell Function.

Ca is an important intracellular second messenger known to regulate several cellular functions. This research aimed to investigate the mechanisms of exercise-induced immunosuppression by measuring intracellular calcium levels, Ca-regulating gene expression, and agonist-evoked proliferation of murine splenic T lymphocytes. Mice were randomly assigned to the control, sedentary group (C), and three experimental groups, which performed a single bout of intensive and exhaustive treadmill exercise.

Chronic Obstructive Pulmonary Disease and the Cardiovascular System: Vascular Repair and Regeneration as a Therapeutic Target.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and encompasses chronic bronchitis and emphysema. It has been shown that vascular wall remodeling and pulmonary hypertension (PH) can occur not only in patients with COPD but also in smokers with normal lung function, suggesting a causal role for vascular alterations in the development of emphysema. Mechanistically, abnormalities in the vasculature, such as inflammation, endothelial dysfunction, imbalances in cellular apoptosis/proliferation, and increased oxidative/nitrosative stress promote development of PH, cor pulmonale, and most probably pulmonary emphysema.

Author Correction: NADPH oxidase subunit NOXO1 is a target for emphysema treatment in COPD.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

NADPH oxidase subunit NOXO1 is a target for emphysema treatment in COPD.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and death worldwide. Peroxynitrite, formed from nitric oxide, which is derived from inducible nitric oxide synthase, and superoxide, has been implicated in the development of emphysema, but the source of the superoxide was hitherto not characterized. Here, we identify the non-phagocytic NADPH oxidase organizer 1 (NOXO1) as the superoxide source and an essential driver of smoke-induced emphysema and pulmonary hypertension development in mice.

Author Correction: High resolution and sensitivity gamma camera with active septa. A first Monte Carlo study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PADC nuclear track detector for ion spectroscopy in laser-plasma acceleration.

The transparent polymer polyallyl-diglycol-carbonate (PADC), also known as CR-39, is widely used as detector for heavy charged particles at low fluence. It allows for detection of single protons and ions via formation of microscopic tracks after etching in NaOH or KOH solutions. PADC combines a high sensitivity and high specificity with inertness towards electromagnetic noise.

Amelioration of elastase-induced lung emphysema and reversal of pulmonary hypertension by pharmacological iNOS inhibition in mice.

Background And Purpose: Chronic obstructive pulmonary disease, encompassing chronic airway obstruction and lung emphysema, is a major worldwide health problem and a severe socio-economic burden. Evidence previously provided by our group has shown that inhibition of inducible NOS (iNOS) prevents development of mild emphysema in a mouse model of chronic tobacco smoke exposure and can even trigger lung regeneration. Moreover, we could demonstrate that pulmonary hypertension is not only abolished in cigarette smoke-exposed iNOS mice but also precedes emphysema development.

Prompt gamma spectroscopy for absolute range verification of C ions at synchrotron-based facilities.

The physical range uncertainty limits the exploitation of the full potential of charged particle therapy. In this work, we face this issue aiming to measure the absolute Bragg peak position in the target. We investigate p, He, C and O beams accelerated at the Heidelberg Ion-Beam Therapy Center.

High resolution and sensitivity gamma camera with active septa. A first Monte Carlo study.

Gamma cameras are of great interest due to their high potential in the field of Nuclear Medicine Imaging. They allow for an early diagnosis of reduced size tumors, and also for a wide variety of preclinical studies with the aim of designing more effective treatments against cancer. In this work we propose a significantly improved multi-pinhole collimator gamma camera and perform a first Monte Carlo analysis of its characteristics.

Riociguat for treatment of pulmonary hypertension in COPD: a translational study.

Chronic obstructive pulmonary disease (COPD), which comprises the phenotypes of chronic bronchitis and emphysema, is often associated with pulmonary hypertension (PH). However, currently, no approved therapy exists for PH-COPD. Signalling of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) axis plays an important role in PH and COPD.

Spectral characterization of laser-accelerated protons with CR-39 nuclear track detector.

CR-39 nuclear track material is frequently used for the detection of protons accelerated in laser-plasma interactions. The measurement of track densities allows for determination of particle angular distributions, and information on the kinetic energy can be obtained by the use of passive absorbers. We present a precise method of measuring spectral distributions of laser-accelerated protons in a single etching and analysis process.

Differential Alterations of the Mitochondrial Morphology and Respiratory Chain Complexes during Postnatal Development of the Mouse Lung.

Mitochondrial biogenesis and adequate energy production in various organs of mammals are necessary for postnatal adaptation to extrauterine life in an environment with high oxygen content. Even though transgenic mice are frequently used as experimental models, to date, no combined detailed molecular and morphological analysis on the mitochondrial compartment in different lung cell types has been performed during postnatal mouse lung development. In our study, we revealed a significant upregulation of most mitochondrial respiratory complexes at protein and mRNA levels in the lungs of P15 and adult animals in comparison to newborns.

Exercise training reverses inflammation and muscle wasting after tobacco smoke exposure.

Long-term cigarette smoking induces inflammatory processes in the pulmonary system that are suggested to "spill over" into systemic inflammation. Regular exercise has been shown to have anti-inflammatory properties. The aim of the study was to investigate the effects of therapeutic exercise on inflammation and muscle wasting in smoke-exposed mice.

Knock out of the NADPH oxidase Nox4 has no impact on life span in mice.

The free radical theory of aging suggests reactive oxygen species as a main reason for accumulation of damage events eventually leading to aging. Nox4, a member of the family of NADPH oxidases constitutively produces ROS and therefore has the potential to be a main driver of aging. Herein we analyzed the life span of Nox4 deficient mice and found no difference when compared to their wildtype littermates.

Simulations of the gain profile and performance of a diode side-pumped QCW Nd:YAG laser.

A design of a diode side-pumped Nd:YAG laser module and simulations of the gain distribution inside the active medium are presented in this paper. The code is based on a nonsequential ray-tracing Monte Carlo method for the light generated by the laser diodes. The fluorescence image of the active medium was analyzed in order to compare it with the simulations, which were found to be in good agreement with experimental data.

Exercise Affects T-Cell Function by Modifying Intracellular Calcium Homeostasis.

Purpose: The study aimed to investigate the effects of chronic moderate exercise on regulation of intracellular calcium signaling as an important link to proliferation capacity in murine splenic T lymphocytes.

Methods: Male CD1 Swiss mice were randomly assigned either to a control group (CG) or an exercise training group (EG). EG mice performed voluntary exercise for 3 months.

Cigarette smoke causes acute airway disease and exacerbates chronic obstructive lung disease in neonatal mice.

Epidemiological evidence demonstrates a strong link between postnatal cigarette smoke (CS) exposure and increased respiratory morbidity in young children. However, how CS induces early onset airway disease in young children, and how it interacts with endogenous risk factors, remains poorly understood. We, therefore, exposed 10-day-old neonatal wild-type and β-epithelial sodium ion channel (β-ENaC)-transgenic mice with cystic fibrosis-like lung disease to CS for 4 days.

Postnatal development of the bronchiolar club cells of distal airways in the mouse lung: stereological and molecular biological studies.

Club (Clara) cells are nonciliated secretory epithelial cells present in bronchioles of distal pulmonary airways. So far, no information is available on the postnatal differentiation of club cells by a combination of molecular biological, biochemical, and stereological approaches in the murine lung. Therefore, the present study was designed to investigate the changes in the club cell secretory proteins (CC10, surfactant proteins A, B and D) and club cell abundance within the epithelium of bronchioles of distal airways during the postnatal development of the mouse lung.

Endurance and Resistance Training Affect High Fat Diet-Induced Increase of Ceramides, Inflammasome Expression, and Systemic Inflammation in Mice.

The study aimed to investigate the effects of differentiated exercise regimes on high fat-induced metabolic and inflammatory pathways. Mice were fed a standard diet (ST) or a high fat diet (HFD) and subjected to regular endurance training (ET) or resistance training (RT). After 10 weeks body weight, glucose tolerance, fatty acids (FAs), circulating ceramides, cytokines, and immunological mediators were determined.

Increased S100A4 expression in the vasculature of human COPD lungs and murine model of smoke-induced emphysema.

Background: Chronic obstructive lung disease (COPD) is a common cause of death in industrialized countries often induced by exposure to tobacco smoke. A substantial number of patients with COPD also suffer from pulmonary hypertension that may be caused by hypoxia or other hypoxia-independent stimuli - inducing pulmonary vascular remodeling. The Ca(2+) binding protein, S100A4 is known to play a role in non-COPD-driven vascular remodeling of intrapulmonary arteries.

Increased cardiovascular disease risk in the HIV-positive population on ART: potential role of HIV-Nef and Tat.

With effective antiretroviral therapy (ART), many HIV-infected people die of diseases other than acquired immune deficiency syndrome (AIDS). In particular, coronary artery disease has emerged as one of most critical complications of HIV infection and a major cause of morbidity and mortality. Although reportedly antiretroviral combination therapy itself may accelerate atherosclerosis by enhancing dyslipidemia, most recent epidemiological studies support the notion that HIV infection itself contributes to cardiovascular disease.