The mechanisms by which metals induce activation of T cells and thus produce allergic and/ or autoimmune reactions are still obscure, and the same is true for the mechanisms that underly T cell cross-reactivity to different heavy metal ions. In the present study, we investigated induction by metals of T cell reactions to cryptic peptides of bovine RNase A. Murine CD4+ T cell hybridomas specific for cryptic RNase peptides presented from Au(III)-treated RNase were used as detection probes. We showed that in vitro treatment of RNase with Pd(II), Pd(IV), Ni(IV), and partially Pt(IV), but not Au(I), Ni(II), or Pt(II), induced presentation of the same cryptic peptides as those presented from Au(III)-treated RNase. That the former heavy metal ions, but not the latter, were able to alter the antigenicity of RNase was reflected by their ability to induce conformational changes of RNase, as detected by circular dichroism spectroscopy. Furthermore, upon immunization against RNase pretreated with these metals, CD4+ T cell hybridomas specific for unidentified cryptic peptides were obtained. In conclusion, "metal-specific" T cell reactions may be directed against cryptic peptides, and metal cross-reactivity in allergic individuals might be due to metal-induced presentation of overlapping, but not identical, panels of cryptic peptides.
Diabetes is a chronic disease which affects around 8.3% of the worldwide population. 1,2 It is estimated that 1 in every 13 persons in Germany has diabetes. 3 Type 2 diabetes mellitus (T2DM) is found in 90% of individuals with diabetes. 4 The current annual German cost associated with T2DM of approximately €11.8 billion in 2010 will exceed €21 billion in 2040, underscoring the major burden of diabetes in this country. 5 Reduction of blood glucose levels in T2DM patients is important since it can prevent microvascular and macrovascular complications. 6-8 If these levels remain high despite the introduction of lifestyle measures such as weight control and physical activity, oral antihyperglycemic medications and insulin treatments can be used in people with T2DM. Several studies have targeted the prescription of antihyperglycemic drugs and the cost of these medications in Germany. 9-10 In 2007, Rathmann and colleagues discovered that there had been a 100% increase in the average cost for antidiabetic medication between 1994 (€86.7) and 2004 (€172.1). 9 More recently, Tamayo et al further found regional and individual social disparities in the cost of overall and newer antihyperglycemic medications unexplained by other confounders. 10 Although these works have shed light on medical and 658746D STXXX10.
The coronavirus pandemic and related restrictions impacted the daily lives of children and youth, partly due to the closure of schools and the absence of outdoor activities. The aim of this study was to investigate, quantify, and critically discuss the effect of the pandemic and related restrictions on consultations pertaining to depression and anxiety disorders in children and adolescents. This retrospective cross-sectional study was based on medical record data from the Disease Analyzer database (IQVIA) and included all children and adolescents aged 2-17 years with at least one visit to one of 168 German pediatric
Approximately one of five tramadol patients was prescribed tramadol in combination therapy. Further research is needed to gain a better understanding of the demographic and clinical factors that have an effect on tramadol prescription patterns in Germany.
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