Identification of gene expression biomarkers to predict clinical response to methotrexate in patients with rheumatoid arthritis.

Objectives: To identify biomarkers at the gene expression level to predict response to methotrexate (MTX) in patients with rheumatoid arthritis (RA).

Methods: MTX-naïve patients with RA were started on MTX and followed up over three months. The disease activity score 28 (DAS28) was used to classify patients into responders and non-responders.

Venipuncture and Blood Collection on Conscious Virginia Opossums (Didelphis virginiana).

We developed a venipuncture technique of the ventral caudal vein in conscious Virginia opossums (Didelphis virginiana) in cage traps, enabling blood sampling without anesthesia. Blood samples were successfully collected from all 28 opossums in this study by this technique. Draw volume of <0.

Probing Different Approaches in Ultraviolet Radiation Personal Dosimetry - Ball Sports and Visiting Parks.

Solar ultraviolet radiation (UVR) continues to be a decisive influencing factor for skin health. Besides acute damage (e.g.

The Anti-Glucocorticoid Receptor Antibody Clone 5E4: Raising Awareness of Unspecific Antibody Binding.

Unspecific antibody binding takes a significant toll on researchers in the form of both the economic burden and the disappointed hopes of promising new therapeutic targets. Despite recent initiatives promoting antibody validation, a uniform approach addressing this issue has not yet been developed. Here, we demonstrate that the anti-glucocorticoid receptor (GR) antibody clone 5E4 predominantly targets two different proteins of approximately the same size, namely AMP deaminase 2 (AMPD2) and transcription intermediary factor 1-beta (TRIM28).

Association between ivy leaves dry extract EA 575 prescriptions and antibiotic use, sick leave duration, and repeated infections in adult patients.

Objectives: The present study aimed to analyze the association between the prescription of ivy leaf dry extract EA 575 (licensed under the trade name Prospan® in Germany) and the incidence of antibiotic use, incident bacterial complications, and days of sick leave in adult patients with cold diseases.

Methods: This retrospective cohort study was based on the IQVIA Disease Analyzer database and included adult patients from 1032 general practices in Germany with a documentation of common cold between 2017 and 2020 (index date) and prescription of either EA 575 or an antibiotic drug within 3 days after index date. 1:1 propensity score matching based on age, sex, index month, physician, health insurance status, and the Charlson Comorbidity Index was carried out.

Bringing Light into Darkness-Comparison of Different Personal Dosimeters for Assessment of Solar Ultraviolet Exposure.

(1) Measuring personal exposure to solar ultraviolet radiation (UVR) poses a major challenges for researchers. Often, the study design determines the measuring devices that can be used, be it the duration of measurements or size restrictions on different body parts. It is therefore of great importance that measuring devices produce comparable results despite technical differences and modes of operation.

Surface AMP deaminase 2 as a novel regulator modifying extracellular adenine nucleotide metabolism.

Adenine nucleotides represent crucial immunomodulators in the extracellular environment. The ectonucleotidases CD39 and CD73 are responsible for the sequential catabolism of ATP to adenosine via AMP, thus promoting an anti-inflammatory milieu induced by the "adenosine halo". AMPD2 intracellularly mediates AMP deamination to IMP, thereby both enhancing the degradation of inflammatory ATP and reducing the formation of anti-inflammatory adenosine.

[Oral glucocorticoids : Therapeutic use and treatment monitoring in inflammatory rheumatic diseases].

Glucocorticoids (GC) have been proven drug substances in rheumatology for more than 70 years. They act very rapidly in high doses through membrane stabilizing effects. Genomic therapeutic effects of GC even in very low doses are mainly due to inhibition of the functions of the transcription factor nuclear factor kappa B (NFkB), which promotes the synthesis of proinflammatory mediators, adhesion molecules and other regulatory proteins.

[Oral glucocorticoids : Therapeutic use and treatment monitoring in inflammatory rheumatic diseases].

Glucocorticoids (GC) have been proven drug substances in rheumatology for more than 70 years. They act very rapidly in high doses through membrane stabilizing effects. Genomic therapeutic effects of GC even in very low doses are mainly due to inhibition of the functions of the transcription factor nuclear factor kappa B (NFkB), which promotes the synthesis of proinflammatory mediators, adhesion molecules and other regulatory proteins.

Glucocorticoids-All-Rounders Tackling the Versatile Players of the Immune System.

Glucocorticoids regulate fundamental processes of the human body and control cellular functions such as cell metabolism, growth, differentiation, and apoptosis. Moreover, endogenous glucocorticoids link the endocrine and immune system and ensure the correct function of inflammatory events during tissue repair, regeneration, and pathogen elimination via genomic and rapid non-genomic pathways. Due to their strong immunosuppressive, anti-inflammatory and anti-allergic effects on immune cells, tissues and organs, glucocorticoids significantly improve the quality of life of many patients suffering from diseases caused by a dysregulated immune system.

Cost-effective reduction of micro pollutants in the water cycle - Case study on iodinated contrast media.

Surface waters, especially in densely populated areas, are facing multiple anthropogenic pressures. Micro pollutants are of growing concern. Improved analytical methods are used to focus on substances like ICM with a (high) potential of hazardous effects against water organisms or the water quality in general ICM are essential for instance in computer tomographic examinations in medical facilities.

The deubiquitination of the PTS1-import receptor Pex5p is required for peroxisomal matrix protein import.

Peroxisomal biogenesis depends on the correct import of matrix proteins into the lumen of the organelle. Most peroxisomal matrix proteins harbor the peroxisomal targeting-type 1 (PTS1), which is recognized by the soluble PTS1-receptor Pex5p in the cytosol. Pex5p ferries the PTS1-proteins to the peroxisomal membrane and releases them into the lumen.

CTLA-4 Mediates Inhibitory Function of Mesenchymal Stem/Stromal Cells.

Mesenchymal stem/stromal cells (MSCs) are stem cells of the connective tissue, possess a plastic phenotype, and are able to differentiate into various tissues. Besides their role in tissue regeneration, MSCs perform additional functions as a modulator or inhibitor of immune responses. Due to their pleiotropic function, MSCs have also gained therapeutic importance for the treatment of autoimmune diseases and for improving fracture healing and cartilage regeneration.

Unraveling the role of hypoxia-inducible factor (HIF)-1α and HIF-2α in the adaption process of human microvascular endothelial cells (HMEC-1) to hypoxia: Redundant HIF-dependent regulation of macrophage migration inhibitory factor.

Hypoxia driven angiogenesis is a prominent feature of tissue regeneration, inflammation and tumor growth and is regulated by hypoxia-inducible factor (HIF)-1 and -2. The distinct functions of HIFs in the hypoxia-induced angiogenesis and metabolic switch of endothelial cells are still unknown and therefore aim of this study. We investigated the role of HIF-1 and -2 in the adaptation of immortalized human microvascular endothelial cells (HMEC-1) to hypoxic conditions (1% O) in terms of angiogenesis, cytokine secretion, gene expression and ATP/ADP-ratio using shRNA-mediated reduction of the oxygen sensitive α-subunits of either HIF-1 or HIF-2 or the combination of both.

Will we ever have better glucocorticoids?

Glucocorticoids are cost-effective drugs with potent anti-inflammatory and immunosuppressive effects. They are used successfully to treat many disorders, including rheumatoid arthritis, polymyalgia rheumatic and other rheumatic diseases. However, these drugs also have the potential to cause adverse effects, particularly if high doses are used for prolonged periods.

Metabolic regulation of inflammation.

Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions.

A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients.

Immunologically restricted patients such as those with autoimmune diseases or malignancies often suffer from delayed or insufficient fracture healing. In human fracture hematomas and the surrounding bone marrow obtained from immunologically restricted patients, we analyzed the initial inflammatory phase on cellular and humoral level via flow cytometry and multiplex suspension array. Compared with controls, we demonstrated higher numbers of immune cells like monocytes/macrophages, natural killer T (NKT) cells, and activated T helper cells within the fracture hematomas and/or the surrounding bone marrow.

Glucocorticoid-targeted therapies for the treatment of rheumatoid arthritis.

The beneficial effects of glucocorticoids are highly regarded in the treatment of inflammatory diseases. In rheumatoid arthritis, these drugs are widely used because they effectively reduce signs and symptoms of the disease, and exert disease-modifying effects. However, both patients and physicians frequently associate glucocorticoids with a variety of adverse effects which hamper adherence.

Modification of the surface of superparamagnetic iron oxide nanoparticles to enable their safe application in humans.

Combined individually tailored methods for diagnosis and therapy (theragnostics) could be beneficial in destructive diseases, such as rheumatoid arthritis. Nanoparticles are promising candidates for theragnostics due to their excellent biocompatibility. Nanoparticle modifications, such as improved surface coating, are in development to meet various requirements, although safety concerns mean that modified nanoparticles require further review before their use in medical applications is permitted.

Immunological characterization of the early human fracture hematoma.

The initial inflammatory phase of fracture healing is of great importance for the clinical outcome. We aimed to develop a detailed time-dependent analysis of the initial fracture hematoma. We analyzed the composition of immune cell subpopulations by flow cytometry and the concentration of cytokines and chemokines by bioplex in 42 samples from human fractures of long bones <72 h post-trauma.

[Long-term glucocorticoid therapy : Is there a safe dosage?].

Glucocorticoids have been successfully used for a long time to treat a wide range of chronic inflammatory diseases. Despite the well-accepted efficacy, possible adverse effects still provoke discussions among patients and physicians. In particular, the long-term use of glucocorticoids at higher dosages may cause unwanted adverse effects; therefore, the question arises if conditions for a safe long-term treatment regimen with these drugs can be defined.

Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force.

There is convincing evidence for the known and unambiguously accepted beneficial effects of glucocorticoids at low dosages. However, the implementation of existing recommendations and guidelines on the management of glucocorticoid therapy in rheumatic diseases is lagging behind. As a first step to improve implementation, we aimed at defining conditions under which long-term glucocorticoid therapy may have an acceptably low level of harm.

Effects of PVA-coated nanoparticles on human T helper cell activity.

Superparamagnetic iron oxide nanoparticles (SPION) are used as high-sensitive enhancer for magnetic resonance imaging, where they represent a promising tool for early diagnosis of destructive diseases such as rheumatoid arthritis (RA). Since we could demonstrate that professional phagocytes are activated by amino-polyvinyl-alcohol-coated-SPION (a-PVA-SPION), the study here focuses on the influence of a-PVA-SPION on human T cells activity. Therefore, primary human CD4+ T cells from RA patients and healthy subjects were treated with varying doses of a-PVA-SPION for 20h or 72h.