IFN-beta modulates the response to TLR stimulation in human DC: involvement of IFN regulatory factor-1 (IRF-1) in IL-27 gene expression

Type I IFN are cytokines which play a central role in host resistance to viral or microbial infections and are important components linking innate and adaptive immunity. We and others have previously demonstrated that the production of IFN-beta by DC following bacterial infections or TLR triggering influences, in an autocrine manner, their maturation. In this study, we investigated whether IFN-beta release modulates the phenotype of the immature DC and their response to a subsequent TLR stimulation. The induction of CD86, HLA-DR, CD38 and B7H1 and the absence of CCR7 and CD83 expression upon IFN-beta treatment suggest that IFN-beta-primed DC remain at the site of infection acquiring an activated phenotype. These results prompted us to investigate the response of IFN-beta-primed DC to TLR stimulation. While IFN-beta pretreatment increases slightly the expression of maturation markers in TLR2- or TLR4-stimulated DC, it is able to modulate selectively the secretion of inflammatory and immuno-regulating cytokines. Interestingly, IL-27p28 subunit was induced by IFN-beta alone or during LPS-induced maturation of DC in a type I IFN-dependent manner through IFN regulatory factor-1 (IRF-1) activation. Taken together, our results shed light on the capacity of IFN-beta to finely tune DC response to invading pathogens.     

Rückenfit – unsere Schule macht mit

Background

Back pain is not only a worldwide problem in adults, but also in children and adolescents. The prevalence rates increase with age. Risk factors for back pain in children are among others asymmetries of the spine, too heavy and asymmetrically carried school backpacks, and a sedentary lifestyle.

Objectives

This paper presents a multifactorial school-based intervention program and the corresponding study protocol for a cluster-randomized, controlled evaluation of this program to address these risk factors.

Materials and methods

The intervention program should be tested on pupils aged 10–12 at a German “Gymnasium” (secondary school) over the course of one school year. It contains 5 lessons on back care, 3 exercise posters for the class room, and exercises for physical education classes that strengthen and mobilize core muscles and train body perception. The evaluation instruments are motoric tests, a back-behavior test, a knowledge test, a clinical–orthopedic examination, and several questionnaires.

Results and conclusions

The presented intervention program and evaluation instruments aim to show one way of planning and evaluating an intervention in the daily school environment. There is a need for high-quality studies on prevention of back pain in children and adolescents. This is a topic that has received little attention in Germany.

     

Delayed Urinary Symptoms Induced by Ketamine

One of the side-effects of ketamine abuse is genito-urinary damage. This report describes a case of a former ketamine user who presented with urinary symptoms associated with ketamine years after stopping consumption. This was a 26-year-old male with a history of ketamine abuse. He started treatment for alcohol dependence at age 19. He smoked marijuana daily and denied any other drug use. During the follow-up, urinary symptoms were evidenced (dysuria, frequency, urgency, incontinence, nocturia, hematuria, and suprapubic pain). Urinary symptoms started two years ago and worsened over time. The patient was referred to a urologist. A cystoscopy revealed lesions compatible with interstitial cystitis like the ones that appear in some ketamine abusers. Given the medical history, the urologist asked him about ketamine consumption and the patient declared a daily use of 50 milligrams intranasally from age 15 to age 17. Given these findings, not reported previously in the medical literature, future research should follow up patients who at some point in their life made an abusive consumption of ketamine in order to understand the pathogenesis and to be able to intervene before clinical disease manifests itself.     

Polyphenolic extract attenuates fatty acid-induced steatosis and oxidative stress in hepatic and endothelial cells

Purpose

Phenolic compounds (PC) of virgin olive oil exert several biochemical and pharmacological beneficial effects. Some dietary PC seem to prevent/improve obesity and metabolic-related disorders such as non-alcoholic fatty liver disease (NAFLD). We investigated the possible effects of PC extracted from olive pomace (PEOP) and of the main single molecules present in the extract (tyrosol, apigenin, oleuropein, p-coumaric and caffeic acid) in protecting hepatocytes and endothelial cells against triglyceride accumulation and oxidative stress.

Methods

Rat hepatoma and human endothelial cells were exposed to a mixture of oleate/palmitate to mimic the condition of NAFLD and atherosclerosis, respectively. Then, cells were incubated for 24 h in the absence or in the presence of PC or PEOP. Different parameters were evaluated, such as lipid accumulation and oxidative stress-related markers.

Results

In hepatic cells, expression of peroxisome proliferator-activated receptors (PPARs) and of stearoyl-CoA desaturase 1 (SCD-1) were assessed as index of lipid metabolism. In endothelial cells, expression of intercellular adhesion molecule-1 (ICAM-1), activation of nuclear factor kappa-B (NF-kB), release of nitric oxide (NO), and wound-healing rate were assessed as index of inflammation.

Conclusion

PEOP extract ameliorated hepatic lipid accumulation and lipid-dependent oxidative imbalance thus showing potential applications as therapeutic agent tuning down hepatosteatosis and atherosclerosis.

     

Stillmonitoring in Deutschland – aktueller Handlungsbedarf und Perspektiven

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Stillmonitoring bezeichnet die systematische Erhebung aktueller, umfassender und genauer Daten zu Stillquoten, Stillverhalten und...     

Bedeutung des Stillens für das Kind

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Muttermilch ist die natürliche Ernährung für Säuglinge. Neben Nährstoffen enthält Muttermilch eine...     

BURDEN 2020—Burden of disease in Germany at the national and regional level

Background

Evidence-based policy measures need non-interest-guided information about the health status of a population and the diseases that affect the population the most. In such cases, a national burden of disease study can provide reliable insights at the regional level.

Aim

This article presents the potential of the BURDEN 2020 project and its expected outcome for Germany at the national and regional level.

Methods

The BURDEN 2020 project uses several indicators including years of life lost (YLL) to cover the impact of mortality and years lived with disability (YLD) to cover morbidity. The sum of both is the measure of population health called disability adjusted life years (DALY).

Results

The study ranks individual diseases and risk factors based on their impact on population health. The burden of disease approach is assumed to be sensitive to subnational differences and may generate immediate benefits for regional planning. The BURDEN 2020 study will pilot a national burden of disease study for Germany that will later be transformed into a continuous data processing and visualization tool. This is done by using, modifying and supplementing the methodology employed by the Global Burden of Disease (GBD) study to better fit the needs of health policy in Germany. This study is aimed at calculating the disease burden for up to 17 preselected diseases. Furthermore, the estimates of burden of disease are attributed to a selected set of risk factors.

Conclusion

The Burden 2020 study will provide the results of a new, health-related data processing system to the public. This includes a noninterest-guided presentation of the burden of disease (DALY) in Germany at the national and regional level.

     

Synthesis,structure, antioxidant activity,and water solubility of trolox ion conjugates

The interaction of trolox with ammonia, alkylamines of different classes, and amino derivatives of heterocyclic compounds, including nitroxyl radicals and alkaloids, led to the production of ammonium salts called ion conjugates (ICs). Five ICs were characterised by X-ray diffraction. This is the first time a wide range of ICs were made from trolox with amines, and ESI-MS data demonstrated they have the potential to generate pseudomolecular [(A^?B⁺)?+?H]⁺ ions. For all obtained trolox ICs, a significant increase (1–3 orders of magnitude) in water solubility was achieved while retaining high antioxidant activity. ICs synthesised from two biologically active fragments may be used to create polyfunctional agents with varying solubility and bioavailability.     

Expanded access to investigational drugs: balancing patient safety with potential therapeutic benefits

Introduction: Expanded access is the use of an investigational product by patients with serious medical conditions without participation in a clinical trial. It is a complicated process involving the collaboration of many parties and pharmaceutical companies. Ongoing efforts focus on accelerating expanded access procedures in the best interest of patients with cancer.

Areas covered: We review the regulatory and ethical challenges encountered in efforts to optimize expanded access.

Expert opinion: In the era of personalized medicine, patients may benefit from novel therapeutic agents that demonstrate encouraging results in early studies. However, drug approval is a lengthy and cumbersome procedure that might exceed the time frame of a life-threatening disease. Expanded access provides options to patients with unmet needs. It may provide informative safety and efficacy data to the manufacturers and the scientific and regulatory organizations.

Ongoing efforts are being made by global governmental and scientific committees, regulatory agencies, and patient organizations to address the ethical and regulatory issues and to optimize the expanded access process. Their goal is to expand access to promising novel drugs for individual patients and to accelerate the necessary procedures while preserving patient safety.