New cardenolides of Convallaria majalis.

A detailed study of the cardiac glycosides of Convallaria majalis L. allowed the detection and structure determination of ten new cardenolides. Four glycosides of bipindogenin (bipindogenin-3-0-6'-deoxy-beta-D-guloside, bipindogenin-3-0-6'-deoxy-beta-D-alloside, bipindogenin-3-0-6'-deoxy-beta-D-allosido-alpha-L-rhamnoside and bipindogenin-3-0-beta-D-alloside) were isolated as well as three derivatives of sarmentologenin (sarmentologenin-3-0-alpha-L-rhamnoside = sarhamnoloside, sarmentologenin-3-0-6' -deoxy-beta-D-guloside and sarmentologenm-3-0-6'-deoxy-beta-D-alloside) and three isomeric glycosides of sarmentosigenin A (sarmentosigenin-3-0-alpha-L-rhamnoside = tholloside, sarmentosigenin-3-0-6'-deoxy-beta-D-guloside and sarmentosigenin-3-0-6'-deoxy-beta-D-alloside). The occurrence of allose, and of the disaccharide rhamnosido-6-deoxy-allose, resp. as the sugar moieties of cardiac glycosides, was detected for the first time.     

Gene therapy perspectives in modulation of wound healing

A variety of reasons can afflict wound healing. Current research is focussed on the acceleration of wound healing by stimulating molecular processes. Gene therapy may offer completely new ways to treat chronic wounds. Possible advantages of gene therapeutic modulation of wound healing might be a long term efficiency, systemic or local regulation of gene expression and low side-effects. Current goals comprise the improvement of transfection efficiency and specificity. In vivo applications are therefore focussed on optimized inducible or even cell-type specific promotors, as well as on improved local application techniques. Studies from our laboratory demonstrate the possibility to combine modern cell culture techniques with different types of gene transfer. This enables the simultaneous grafting of manipulated cells to the wound with the continuous delivery of specific proteins of interest. Experimentally, this lead to accelerated closure of partial and full thickness animal wounds. Clinically, gene therapy for the treatment of chronic wounds seems to be a realistic goal within the next years and might be applicable for a variety of novel indications.     

Selective Mutistn: A Population-based Study: A Research Note

Seven-year-olds to 15-year-olds in 2 school districts of Göteborg, Sweden, were screened for selective mutism by their teachers and follow-up was achieved for a full school year. Three girls and 2 boys met DSM-IV criteria for selective mutism and a further 25 had a combination of shyness and reticence that did not amount to clinical disorder. The rate of typical selective mutism was 18 in 10,000 children. Shyness/reticence occurred in 89 in 10,000 children. Selective mutism was more common than suggested by earlier studies. Teachers of school age children need to be better informed about its existence.     

The proto-oncogene KRAS is targeted by miR-200c

The GTPase K-ras is involved in a variety of cellular processes such as differentiation, proliferation and survival. However, activating mutations, which frequently occur in many types of cancer, turn KRAS into one of the most prominent oncogenes. Likewise, miR-200c is a key player in tumorigenesis functioning as a molecular switch between an epithelial, non-migratory, chemosensitive and a mesenchymal, migratory, chemoresistant state. While it has been reported that KRAS is modulated by several tumor suppressor miRNAs, this is the first report on the regulation of KRAS by miR-200c, both playing a pivotal role in oncogenesis. We show that KRAS is a predicted target of miR-200c and that the protein expression of KRAS inversely correlates with the miR-200c expression in a panel of human breast cancer cell lines. KRAS was experimentally validated as a target of miR-200c by Western blot analyses and luciferase reporter assays. Furthermore, the inhibitory rffect of miR-200c-dependent KRAS silencing on proliferation and cell cycle was demonstrated in dfferent breast and lung cancer cell lines. Thereby, the particular role of KRAS was dissected from the role of all the other miR-200c targets by specific knockdown experiments using siRNA against KRAS. Cell lines harboring an activating KRAS mutation were similarly affected by miR-200c as well as by the siRNA against KRAS. However, in a cell line with wild-type KRAS only miR-200c was able to change proliferation and cell cycle. Our findings suggest that miR-200c is a potent inhibitor of tumor progression and therapy resistance, by regulating a multitude of oncogenic pathways including the RAS pathway. Thus, miR-200c may cause stronger anti-tumor efffects than a specific siRNA against KRAS, emphasizing the potential role of miR-200c as tumor suppressive miRNA     

Inhalationstherapie bei Atemwegserkrankungen im Kindesalter

In children with airway diseases the administration of drugs via inhalers is the most important treatment modality. The prevalence of respiratory problems, such as bronchial asthma or virus-induced wheezing in children is high and inhalation therapy is frequently prescribed. The following article gives an overview of the drugs used for inhalation therapy detailing mode of action and administration. It is known that errors are often made by children and parents when using inhalers; therefore, a special emphasis is placed on the correct inhalation technique, pitfalls and patient education. More advanced technologies have allowed the development of a new generation of medicines and inhaler systems and this process is ongoing. It is to be expected that more specific therapeutic options will be available in the future in particular for the group of patients with chronic airway diseases. Detailed education, tailored to the product is already a key element for effective use of these treatments and will be even more so in the foreseeable future.     

Extensive hydroa vacciniforme

Hydroa Vaciniforme is a very rare photodermatosis that is mainly seen in childhood. An 18 year old female student reported that since the age of 5 she has been suffering necrotic lesions and vesicles lesions in exposed areas, leaving asymptomatic varioliform scars, which worsened in summer. Light microscopy showed epidermal necrosis with lymphocytic infiltration. Sunscreens were prescribed with light improvement.