Treg Vaccination in Autoimmune Type 1 Diabetes

Foxp3⁺ regulatory T (Treg) cells are critical contributors to the establishment and maintenance of immunological self-tolerance. Autoimmune type 1 diabetes (T1D) is characterized by the loss of self-tolerance to the insulin-producing β cells in the pancreas and the destruction of β cells, resulting in the development of chronic hyperglycemia at diagnosis. The application of strong-agonistic T-cell receptor ligands provided under subimmunogenic conditions functions as a critical means for the efficient de novo conversion of naive CD4⁺ T cells into Foxp3⁺ Treg cells. The specific induction of Treg cells upon supply of strong-agonistic variants of certain self-antigens could therefore function as a critical instrument in order to achieve safe and specific prevention of autoimmunity such as T1D via the restoration of self-tolerance. Such immunotherapeutic strategies are being developed, and in the case of T1D aim to restrict autoimmunity and β-cell destruction. In this review, we discuss the requirements and opportunities for Treg-based tolerance approaches with the goal of interfering with autoimmune T1D.     

Genetische Ätiologie bei chronisch-entzündlichen Darmerkrankungen

Crohn’s disease and ulcerative colitis are the two main forms of inflammatory bowel disease. Inflammatory bowel diseases have a life time prevalence of up to 1?% in western industrialized countries. It is generally proposed that genetic susceptibility, which is much more widespread in the population, needs (unknown) factors in lifestyle in order to lead to disease manifestation. Systematic genome-wide association studies opened a new level of understanding of the risk architecture of inflammatory bowel diseases. This has led to the concept that barrier problems on the level of the intestinal epithelial cells may be a main driver in disease etiopathogenesis. Many of the newly discovered disease genes are not only relevant for inflammatory bowel disease but also for other disorders. This has initiated a large research interest in co-morbidities, which appear to be overlooked on the clinical side, too. Novel therapies should address the primary disease mechanisms and therefore provide causal interventions. Endpoints should include the avoidance of co-morbidities, which may be a limiting factor for patients with chronically active disease.     

Orange Juice and Cancer Chemoprevention

Orange juice (OJ) is among the most consumed fruit juices worldwide, and its chemopreventive action is fairly addressed in the literature. This review critically presents the available evidence linking OJ with cancer chemoprevention and on discussing the putative mechanisms and negative health effects. The chemopreventive action of OJ is related to its effect on metabolic enzymes and its antiinflammatory, cytoprotective/apoptotic, hormonal, cell signaling-modulating, antioxidant, and antigenotoxic effects. Most studies on OJ are in vitro, and few are conducted in vivo. Results from in vitro studies must be interpreted carefully because these findings do not consider in vivo bioavailability. However, such results are useful for studying the impact of different processing and storage methods on OJ's chemopreventive effect. Evidence of OJ's chemoprevention in humans is limited. OJ is antimutagenic in bacteria and antigenotoxic in humans and rodents. Studies using rodent cancer models showed that OJ is cancer chemopreventive, influencing either the induction stage or the promotion stage. The composition and, therefore, the chemopreventive action of OJ might be influenced by different cultivars, climates, extraction methods, packaging, storage temperatures, and shelf lives, among other factors. Epidemiological studies and randomized controlled intervention studies in humans evaluating the chemopreventive effect of OJ, taking into consideration variability in OJ composition, are needed.     

Community-Based Accompaniment and Psychosocial Health Outcomes in HIV-Infected Adults in Rwanda: A Prospective Study

We examined whether the addition of community-based accompaniment to Rwanda’s national model for antiretroviral treatment (ART) was associated with greater improvements in patients’ psychosocial health outcomes during the first year of therapy. We enrolled 610 HIV-infected adults with CD4 cell counts under 350 cells/μL initiating ART in one of two programs. Both programs provided ART and required patients to identify a treatment buddy per national protocols. Patients in one program additionally received nutritional and socioeconomic supplements, and daily home-visits by a community health worker (“accompagnateur”) who provided social support and directly-observed ingestion of medication. The addition of community-based accompaniment was associated with an additional 44.3 % reduction in prevalence of depression, more than twice the gains in perceived physical and mental health quality of life, and increased perceived social support in the first year of treatment. Community-based accompaniment may represent an important intervention in HIV-infected populations with prevalent mental health morbidity.     

Diagnostik und Therapie der ligamentären Ellenbogeninstabilitäten

Posttraumatic or acute instability of the elbow can develop after complete or incomplete dislocation of the elbow. Isolated medial collateral ligament ruptures can be a result of valgus trauma and lateral collateral ligament ruptures of pivot shift or varus trauma. Chronic instability of the elbow may occur after conservative or operative treatment of a traumatic ligament rupture without stable healing. Repetitive overuse in sports or professions may also cause chronic instability. This article provides the reader an overview about current concepts in elbow instability.     

The use of Ginkgo biloba in healthy elderly

To promote health-conscious behavior in the aging society and gain insight into the sources of knowledge on which preventive strategies are based, analyzing the behavior of elderly people who are recognized as highly health conscious may be useful. We focused on the use of Ginkgo biloba, which is commonly considered to be effective in preventing cognitive decline and dementia, among elderly adults. A total of 1,672 questionnaires were distributed among geriatric participants (60–94 years) who attended university lectures at 22 universities throughout Germany. Response rate was 36.1 %. We collected data on demographic characteristics, preventive strategies (use of Ginkgo and other supplements), health-conscious behavior, sources of knowledge concerning health behavior, and factors associated with the participants’ concept of aging. The prevalence of Ginkgo use was 15.3 %. Ginkgo was assumed to be effective for cognitive enhancement and the treatment of cognitive decline by two thirds of the surveyed participants and one third believed Ginkgo to be effective for preventing dementia. Ginkgo use was significantly higher among participants using natural remedies and herbal and food supplements. The use of Ginkgo was recommended by physicians (57.3 %), chemists (16 %), and healthcare magazines (10.7 %). Food supplements were taken by 65.8 % of the sample: this percentage was significantly higher among subjects who exhibited health-conscious behavior. “Knowledge” about strategies to enhance cognition or prevent cognitive decline among the elderly do not appear to be evidence based. Thus, there is a need to establish reliable and independent sources of scientific information for healthcare professionals and the general public.     

Caspase-mediated degradation of human 5-lipoxygenase in B lymphocytic cells

5-Lipoxygenase (5-LO) is a tightly regulated enzyme in the synthesis of bioactive lipids from arachidonic acid. Here, we demonstrate that 5-LO is regulated by caspases, which are signaling molecules that control critical biological processes by means of specific limited proteolysis. Cell splitting of the Epstein-Barr virus-transformed B lymphocytic cell line BL41-E95-A caused a pronounced, but transient, reduction of functional 5-LO protein, accompanied by the appearance of a 62-kDa 5-LO cleavage product. In parallel, splitting of BL41-E95-A cells induced activation of caspase-6 (casp-6) and casp-8. Caspase activation and 5-LO degradation were blocked by the protein-synthesis inhibitor cycloheximide, and cell-permeable peptide inhibitors of casp-6 and casp-8 prevented 5-LO cleavage. Activation of casp-6 and casp-8 was connected to subsequent enhancement of cell proliferation, whereas selective caspase inhibition blocked cell growth. Last, isolated human 5-LO was cleaved by recombinant casp-6 in vitro to a 58-kDa fragment. Based on site-directed mutagenesis studies, 5-LO is cleaved by casp-6 after Asp-170, which in a homology-based 3D model of 5-LO is located on the enzyme periphery. We suggest that splitting of BL41-E95-A cells induces de novo synthesis of a protein involved in the activation of casp-6, which cleaves 5-LO.