Cellular prion protein directly interacts with and enhances lactate dehydrogenase expression under hypoxic conditions.

Although a physiological function of the cellular prion protein (PrP(c)) is still not fully clarified, a PrP(c)-mediated neuroprotection against hypoxic/ischemic insult is intriguing. After ischemic stroke prion protein knockout mice (Prnp(0/0)) display significantly greater lesions as compared to wild-type (WT) mice. Earlier reports suggested an interaction between the glycolytic enzyme lactate dehydrogenase (LDH) and PrP(c).

Unilateral optic neuropathy following subdural hematoma: a case report.

Introduction: Unilateral optic neuropathy is commonly due to a prechiasmatic affliction of the anterior visual pathway, while losses in visual hemifields result from the damage to brain hemispheres. Here we report the unusual case of a patient who suffered from acute optic neuropathy following hemispherical subdural hematoma. Although confirmed up to now only through necropsy studies, our case strongly suggests a local, microcirculatory deficit identified through magnetic resonance imaging in vivo.

Signal transduction by the atopy-associated human thymic stromal lymphopoietin (TSLP) receptor depends on Janus kinase function.

Thymic stromal lymphopoietin (TSLP) is an interleukin-(IL)-7-like cytokine with emerging pathological importance for the development of atopic diseases such as allergic asthma bronchiale. The TSLP receptor (TSLPR), a heterodimeric type I cytokine receptor, shares the IL-7R alpha-subunit with the IL-7 receptor system. The specific TSLPR alpha-chain shows similarities with the gammac receptor chain, but has some unusual features within the receptor family in both its ligand-binding and cytoplasmic domain.

Optic nerve lesion increases cell proliferation and nestin expression in the adult mouse eye in vivo.

In the naïve adult rodent eye cell proliferation does not occur. The aim of this in vivo study was to evaluate if quiescent putative progenitor-like cells within the adult mouse eye can be activated by optic nerve (ON) injury. For a comprehensive analysis, three areas were assessed: the ON, the neural retina, and the ciliary body (CB).

Signal transduction in the footsteps of goethe and schiller.

The historical town of Weimar in Thuringia, the "green heart of Germany" was the sphere of Goethe and Schiller, the two most famous representatives of German literature's classic era. Not yet entirely as influential as those two cultural icons, the Signal Transduction Society (STS) has nevertheless in the last decade established within the walls of Weimar an annual interdisciplinary Meeting on "Signal Transduction - Receptors, Mediators and Genes", which is well recognized as a most attractive opportunity to exchange results and ideas in the field.The 12th STS Meeting was held from October 28 to 31 and provided a state-of-the-art overview of various areas of signal transduction research in which progress is fast and discussion lively.

Signal transduction around thymic stromal lymphopoietin (TSLP) in atopic asthma.

Thymic stromal lymphopoietin (TSLP), a novel interleukin-7-like cytokine, triggers dendritic cell-mediated inflammatory responses ultimately executed by T helper cells of the Th2 subtype. TSLP emerged as a central player in the development of allergic symptoms, especially in the airways, and is a prime regulatory cytokine at the interface of virus- or antigen-exposed epithelial cells and dendritic cells (DCs). DCs activated by epithelium-derived TSLP can promote naïve CD4+ T cells to adopt a Th2 phenotype, which in turn recruite eosinophilic and basophilic granulocytes as well as mast cells into the airway mucosa.

Overexpression of cellular prion protein alters postischemic Erk1/2 phosphorylation but not Akt phosphorylation and protects against focal cerebral ischemia.

Purpose: The physiological function of the cellular prion protein (PrPC) is still unclear. A growing body of evidence suggests that PrPC has neuroprotective properties and that its deletion increases susceptibility to focal cerebral ischemia. The purpose of this study was to elucidate the role of PrPC overexpression in ischemic brain injury in vivo.

Interleukin-13 acts as an apoptotic effector on lung epithelial cells and induces pro-fibrotic gene expression in lung fibroblasts.

Background: IL-13 promotes acute allergic asthma and is discussed to play a role in late asthmatic features such as fibrotic processes and airway remodelling. The contributions of IL-13-mediated mechanisms to subepithelial events related to fibrosis are not yet settled.

Objective: We investigated the impact of IL-13 on lung epithelial cells as apoptotic effector and on lung fibroblasts as inducer of pro-fibrotic gene expression.

Efficacy and treatment satisfaction of once-daily insulin glargine plus one or two oral antidiabetic agents versus continuing premixed human insulin in patients with type 2 diabetes previously on long-term conventional insulin therapy: the Switch pilot study.

Background: Addition of the long-acting basal human insulin analogue insulin glargine (LANTUS) to the treatment regimen of patients with inadequate glycaemic control on oral antidiabetic drugs (OADs) alone has previously been evaluated as effective, safe and convenient. This pilot study aimed to establish whether insulin glargine plus OADs is effective in Type 2 diabetes patients previously poorly controlled on premixed insulin therapy.

Methods: In an open, controlled, randomized, parallel-group, single-centre, 16-week pilot study, 52 patients (age 65.

Efficacy and treatment satisfaction of once-daily insulin glargine plus one or two oral antidiabetic agents versus continuing premixed human insulin in patients with Type 2 diabetes previously on long-term conventional insulin therapy: the SWITCH Pilot Study.

Background: Addition of the long-acting basal human insulin analogue insulin glargine (LANTUS) to the treatment regimen of patients with inadequate glycaemic control on oral antidiabetic drugs (OADs) alone has previously been evaluated as effective, safe and convenient. This pilot study aimed to establish whether insulin glargine plus OADs is effective in Type 2 diabetes patients previously poorly controlled on premixed insulin therapy.

Methods: In an open, controlled, randomized, parallel-group, single-centre, 16-week pilot study, 52 patients (age 65.

Therapeutic potential of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors for the treatment of retinal and eye diseases.

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, generically termed statins, are widely prescribed for their cholesterol-lowering properties. In addition to lipid-lowering properties, statins have pleiotropic effects including anti-inflammatory, anti-apoptotic, and antiproliferative effects. Recently, data from experimental and observational studies have indicated that statins could also become a treatment option for diseases of the central nervous system (CNS).

A primary culture technique of adult retina for regeneration studies on adult CNS neurons.

This protocol details a tissue culture technique that allows for quantified regeneration studies on adult retinal ganglion cells (RGCs), that is, CNS neurons. The method may also allow for elucidation of molecular cues, for example of signals relevant in neuronal survival and axon regeneration. The procedure relies on fractioned stripe culture of previously injured retina in defined culture media.

Grafting of thrombopoietin-mimetic peptides into cystine knot miniproteins yields high-affinity thrombopoietin antagonists and agonists.

Thrombopoietin is the primary regulator of platelet production. We exploited two naturally occurring miniproteins of the inhibitor cystine knot family as stable and rigid scaffolds for the incorporation of peptide sequences that have been shown to act as high-affinity thrombopoietin antagonists. Several miniproteins that antagonistically block thrombopoietin-mediated receptor activation were identified using a microscale reporter assay.

Diabetes, insulin, and risk of cancer.

Up to now, the studies involving diabetes mellitus and malignancies show controversial results: Many of them have found incidences of malignancies that were comparable or even lower than those in nondiabetic subjects; others conclude that diabetes mellitus is linked to a higher incidence of malignancies and/or a predictor of mortality from cancer. Insulin and its precursors, pro- and pre-proinsulin, have been shown to have some homology to the insulin-like growth factors, but, moreover they have some affinity to bind at receptors of the tumor growth factor and some hybrids too. Hence, an association between diabetes mellitus, insulin, hyperinsulinaemia, and carcinogenesis appears plausible.

Statin-mediated protective effects in the central nervous system: general mechanisms and putative role of stress proteins.

Purpose: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or "statins", are used as cholesterol-lowering agents worldwide. This review, focused on recent experimental and clinical data, summarizes general mechanisms of statin actions underlying neuroprotective effects in the central nervous system (CNS) and presents evidence for putative mechanisms involving heat shock proteins and the survival-related PI-3K/Akt pathway that may be beneficial for the treatment of neurological disorders.

Methods: We carried out a medline search on statin actions, with respect to biochemical pathways and signal transduction on the one hand, and clinical studies in neurologic and retinal diseases on the other hand.

Regulation of GDNF and its receptor components GFR-alpha1, -alpha2 and Ret during development and in the mature retino-collicular pathway.

The development of the retino-tectal projection as part of the central visual pathway is accomplished around postnatal day (P) 10-14 in rodents, and trophic factors are important for topographic refinement of this projection. Emerging data indicate that GDNF may influence synaptic plasticity of this projection. To date, maturation-dependent kinetics of GDNF release and expression and biological function of single GDNF receptors along the retino-collicular pathway are ill-defined.

Structured diabetes therapy and education improves the outcome of patients with insulin treated diabetes mellitus. The 10 year follow-up of a prospective, population-based survey on the quality of diabetes care (the JEVIN Trial).

Aims/hypothesis: JEVIN (Jena's St. Vincent Trial) is a prospective, 10 year follow-up, population-based survey of all insulin treated patients with type 1 and type 2 diabetes mellitus aged 16 to 60 years and living in the city of Jena (100,000 inhabitants), Thuringia, Germany. It aims to show the effects of implementation of the St.

Blockade of interleukin-13-mediated cell activation by a novel inhibitory antibody to human IL-13 receptor alpha1.

Interleukin-13 (IL-13) is a cytokine with a crucial role in the development of allergic asthma. The IL-13 receptor shares the IL-4Ralpha subunit with the IL-4R system, but contains as a specific component the IL-13Ralpha1 chain. Blocking signal release by IL-13 without affecting IL-4 function is a potentially interesting therapeutical option for the treatment of asthma.

Post-transplant diabetes mellitus: risk factors, frequency of transplant rejections, and long-term prognosis.

Background: Estimates of the incidence of new-onset diabetes after renal transplantation vary between 2% and 54%. It was the aim of the present trial to study the prevalence of post-transplant diabetes mellitus (DM), the risk factors, the frequency of transplant rejections, and the long-term prognosis.

Methods: We studied all consecutive patients with endstage renal disease, but without DM who received kidney transplantation at our center since 1992 (n = 253; age, 52.

Erythropoietin promotes regeneration of adult CNS neurons via Jak2/Stat3 and PI3K/AKT pathway activation.

The cytokine hormone erythropoietin (EPO) has proved neuroprotective in CNS injury, and clinical trials for ischemic stroke are ongoing. The capability of EPO to restore postmitotic CNS architecture and function by fibre regeneration has not been examined. Here, we compared in vitro outgrowth capacity of adult retinal ganglion cells (RGCs) following optic nerve (ON) lesion in the presence and absence of EPO.

Long-term prognosis of patients after kidney transplantation: a comparison of those with or without diabetes mellitus.

Background: Compared with non-diabetic subjects, patients with type 2 diabetes and end-stage renal disease (ESRD) have seldom been selected for renal transplantation. It was the aim of this study to compare the long-term prognoses of the two groups of patients after transplantation and to identify factors associated with allograft rejection.

Methods: In a retrospective analysis, we studied all 333 consecutive patients who received a kidney transplant at our centre since 1992.

Improvement of the quality of diabetes control and decrease in the concentrations of AGE-products in patients with type 1 and insulin-treated type 2 diabetes mellitus: results from a 10 year-prospective, population-based survey on the quality of diabetes care in Germany (JEVIN).

Background: Advanced glycation end (AGE)-products are a complex group of compounds that have been implicated in diabetes related long-term complications. Up to the present only few data exist about serum levels of the AGE-proteins N-epsilon-Carboxymethyllysine (CML) and pentosidine in patients with diabetes mellitus.

Patients And Methods: In the present 10-year, population-based trial of a selection-free cohort of patients with insulin-treated diabetes mellitus, serum CML and pentosidine levels were examined in correlation to the patients' quality of diabetes control and the prevalence of diabetes related long-term complications.

Structured treatment and teaching of patients with Type 2 diabetes mellitus and impaired cognitive function--the DICOF trial.

Background: Patient education is integral part of any diabetes therapy in Germany, but elderly patients are not able to follow the variety of topics comprising standard treatment and teaching programmes (TTP), primarily due to impaired neuropsychological function. This leads to deficits in diabetes knowledge and hindered ability for diabetes self-management.

Aim: To evaluate structured TTP for geriatric patients with impaired cognitive function.