Inflammatory processes play essential roles in the pathogenesis of tendinitis and tendinopathy. These events are accompanied by catabolic processes initiated by pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Pharmacological treatments for tendinitis are restricted to the use of non-steroidal anti-inflammatory drugs. Recent studies in various cell models have demonstrated that curcumin targets the NF-κB signaling pathway. However, its potential for the treatment of tendinitis has not been explored. Herein, we used an in vitro model of human tenocytes to study the mechanism of curcumin action on IL-1β-mediated inflammatory signaling. Curcumin at concentrations of 5–20 μm inhibited IL-1β-induced inflammation and apoptosis in cultures of human tenocytes. The anti-inflammatory effects of curcumin included down-regulation of gene products that mediate matrix degradation (matrix metalloproteinase-1, -9, and -13), prostanoid production (cyclooxygenase-2), apoptosis (Bax and activated caspase-3), and stimulation of cell survival (Bcl-2), all known to be regulated by NF-κB. Furthermore, curcumin suppressed IL-1β-induced NF-κB activation via inhibition of phosphorylation and degradation of inhibitor of κBα, inhibition of inhibitor of κB-kinase activity, and inhibition of nuclear translocation of NF-κB. Furthermore, the effects of IL-1β were abrogated by wortmannin, suggesting a role for the phosphatidylinositol 3-kinase (PI-3K) pathway in IL-1β signaling. Curcumin suppressed IL-1β-induced PI-3K p85/Akt activation and its association with IKK. These results demonstrate, for the first time, a potential role for curcumin in treating tendon inflammation through modulation of NF-κB signaling, which involves PI-3K/Akt and the tendon-specific transcription factor scleraxis in tenocytes.
Since 2015 a significant increase in tuberculosis cases is notified in Germany, mostly due to rising numbers of migrants connected to the recent refugee crisis. Because of the low incidence in previous years, knowledge on tuberculosis is more and more limited to specialized centers. However, lung specialist and healthcare workers of other fields have contact to an increasing number of tuberculosis patients. In this situation, guidance for the management of standard therapy and especially for uncommon situations will be essential. This new guideline on tuberculosis in adults gives recommendations on diagnosis, treatment, prevention and prophylaxis. It provides a comprehensive overview over the current knowledge, adapted to the specific situation in Germany. The German Central Committee against Tuberculosis (DZK e. V.) realized this guideline on behalf of the German Respiratory Society (DGP). A specific guideline for tuberculosis in the pediatrics field will be published separately. Compared to the former recommendations of the year 2012, microbiological diagnostics and therapeutic drug management were given own sections. Chapters about the treatment of drug-resistant tuberculosis, tuberculosis in people living with HIV and pharmacological management were extended. This revised guideline aims to be a useful tool for practitioners and other health care providers to deal with the recent challenges of tuberculosis treatment in Germany.
Experimental reproductive and developmental toxicity studies with polychlorinated biphenyls (PCBs) are reviewed in brief to determine their relevance for current environmental exposure of humans during the prenatal and postnatal developmental periods. Additional material is published in electronic form only, which contains graphic overviews on individual PCBs and various mixtures that are linked with the relevant citations. In this comprehensive article we focus on interactions of PCBs with biological substrates that could mediate adverse effects observed in experimental animals and in children, and the shortcomings of many of the animal studies available. A main point of criticism involves the relative lack of animal data on several of those persistent congeners, either as individual compounds or as environmentally relevant mixtures, which are currently used as a measure of human exposure. Experimental studies in animals are frequently conducted with commercial PCB mixtures, a test design that does not reflect the exposure situation in humans. Important improvements of animal experiments could be achieved by more complete reporting of litter data (pre- and post-natal losses, toxic signs in the dam and the offspring, birth weights and postnatal growth data), the inclusion of endpoints that have been found previously to be affected by PCBs, and measurements of internal exposure data.
Endocrine disruption is a specific form of toxicity, where natural and/or anthropogenic chemicals, known as “endocrine disruptors” (EDs), trigger adverse health effects by disrupting the endogenous hormone system. There is need to harmonize guidance on the regulation of EDs, but this has been hampered by what appeared as a lack of consensus among scientists. This publication provides summary information about a consensus reached by a group of world-leading scientists that can serve as the basis for the development of ED criteria in relevant EU legislation. Twenty-three international scientists from different disciplines discussed principles and open questions on ED identification as outlined in a draft consensus paper at an expert meeting hosted by the German Federal Institute for Risk Assessment (BfR) in Berlin, Germany on 11–12 April 2016. Participants reached a consensus regarding scientific principles for the identification of EDs. The paper discusses the consensus reached on background, definition of an ED and related concepts, sources of uncertainty, scientific principles important for ED identification, and research needs. It highlights the difficulty in retrospectively reconstructing ED exposure, insufficient range of validated test systems for EDs, and some issues impacting on the evaluation of the risk from EDs, such as non-monotonic dose–response and thresholds, modes of action, and exposure assessment. This report provides the consensus statement on EDs agreed among all participating scientists. The meeting facilitated a productive debate and reduced a number of differences in views. It is expected that the consensus reached will serve as an important basis for the development of regulatory ED criteria.
Changes in the resistance situation and newly recognized adverse reactions require a continuing adjustment of therapeutic recommendations and constant educational efforts in the field of antimicrobial therapy.
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