[Nutritional Therapy for Children and Adolescents with Autism Spectrum Disorders: What is the Evidence?]. / Ernährungstherapie bei Autismus-Spektrum-Störungen im Kindes- und Jugendalter: wie ist die Evidenz?

BACKGROUND: Autism spectrum disorders (ASDs) are a group of developmental disabilities in childhood and adolescence. Beside genetic predisposition also environmental influences may contribute to the ASD pathogenesis. Family members of children and adolescents with ASD often ask for specific diets to alleviate ASD-associated symptoms. The aim of this review is to provide evidence-based data on nutritional interventions for children and adolescents with ASD, thus enabling practitioners to competently assess these diets. METHODS: Applying defined inclusion and exclusion criteria, a systematic literature research in PubMed, Cinahl and The Cochrane Library was conducted. Studies published earlier than 1999 were excluded. Study quality was assessed by using the CONSORT, STROBE or PRISMA checklist, respectively. RESULTS: 12 randomised controlled studies and 2 non-controlled studies could be included in the evaluation (n=971). There is no proven efficacy of the widely used gluten-free casein-free diets (GFCF), and no respective predictive marker has been proven significant. CONCLUSION: Based on available data, no evidence based recommendations regarding nutritional interventions for children and adolescents with autism spectrum disorders can be made. Future studies need to clarify whether particular patients may yet benefit from certain diets.

[The PRISCUS list in clinical routine. Practicability and comparison to international PIM lists]. / Die PRISCUS-Liste im klinischen Test. Praktikabilität und Vergleich mit internationalen PIM-Listen.

BACKGROUND: Certain drugs are classified as potentially inappropriate medications (PIM) for the elderly. In 2010, the PRISCUS list was published, specifically designed for its applicability in the German pharmaceutical market. The aim of this study was to evaluate the PRISCUS list compared to international PIM lists. METHODS: Based on selected PIM lists (PRISCUS, STOPP/START, Beers), the medications of 308 patients at a clinic of geriatric rehabilitation were screened for PIMs. Applying START criteria, omission of indicated drug therapies was detected. RESULTS: Regarding the rate of PIM detection, the PRISCUS list was less sensitive than the application of STOPP criteria. While hospitalized, the mean number of administered PIMs per patient was 1.2 based on STOPP criteria and 0.5 based on the PRISCUS list. The lowest number of PIMs per patient was detected by applying the Beers list (0.4 PIMs). CONCLUSION: The Beers list should not be used in the German pharmaceutical market. The amendment of diagnosis-related STOPP criteria to the PRISCUS list would be useful to significantly advance therapeutic success and drug safety in the elderly.

Selective ETAR antagonist atrasentan inhibits hypoxia-induced breast cancer cell invasion.

Tumour hypoxia, being widespread in solid tumours, is related to an increased risk of invasion and metastasis as well as to resistance to chemotherapy and radiotherapy. Hypoxia-inducible factor-1alpha (HIF-1alpha) has emerged as the key regulator of the cellular response to hypoxia. In primary breast cancers, HIF-1alpha is overexpressed, and high levels of HIF-1alpha predict for early relapse and increased metastasis. The endothelin (ET) axis, comprising the peptides ET-1, -2, -3 and their receptors A (ETAR) and B (ETBR), is another regulatory system of major relevance in human breast cancer. However, little is known about the interaction of HIF-1alpha and the ET axis in breast carcinomas. Therefore, we analysed expression of HIF-1alpha and the ET axis in 600 breast cancer tissue samples by immunohistochemistry, observing a significant correlation between expression of HIF-1alpha and ET-1 (P<0.001). In vitro, hypoxia was found to double ET-1 secretion of MCF-7 breast cancer cells (203.5% of controls; P<0.001), thereby promoting an invasive phenotype. Of note, real-time PCR analysis revealed that the increase of ET-1 was not due to enhanced transcription of the ET-1 gene. In invasion assays, breast cancer cell invasiveness was strongly increased by hypoxia (150.0% of controls; P=0.007). Most important, this increase was completely inhibited by the selective ETAR antagonist atrasentan. In conclusion, we provide evidence for a relevant interaction between hypoxia and the ET axis in breast cancer cells. Our data suggest that tumour hypoxia induces breast carcinoma invasiveness by releasing intracellularly stored ET-1. However, induction of invasiveness may be inhibited by selective ETAR antagonism, thus emphasising the promising status of the ET axis as a therapeutic target in breast cancer.