Building-up of a DNA barcode library for true bugs (insecta: hemiptera: heteroptera) of Germany reveals taxonomic uncertainties and surprises.

During the last few years, DNA barcoding has become an efficient method for the identification of species. In the case of insects, most published DNA barcoding studies focus on species of the Ephemeroptera, Trichoptera, Hymenoptera and especially Lepidoptera. In this study we test the efficiency of DNA barcoding for true bugs (Hemiptera: Heteroptera), an ecological and economical highly important as well as morphologically diverse insect taxon.

Luminescent dual sensors reveal extracellular pH-gradients and hypoxia on chronic wounds that disrupt epidermal repair.

Wound repair is a quiescent mechanism to restore barriers in multicellular organisms upon injury. In chronic wounds, however, this program prematurely stalls. It is known that patterns of extracellular signals within the wound fluid are crucial to healing.

Penetration of normal, damaged and diseased skin--an in vitro study on dendritic core-multishell nanotransporters.

A growing intended or accidental exposure to nanoparticles asks for the elucidation of potential toxicity linked to the penetration of normal and lesional skin. We studied the skin penetration of dye-tagged dendritic core-multishell (CMS) nanotransporters and of Nile red loaded CMS nanotransporters using fluorescence microscopy. Normal and stripped human skin ex vivo as well as normal reconstructed human skin and in vitro skin disease models served as test platforms.

Increased cutaneous absorption reflects impaired barrier function of reconstructed skin models mimicking keratinisation disorders.

The aim of this study was to assess a recently established 3D model of congenital ichthyosis, representing severe epidermal barrier function defects, for skin penetration and permeation. We have generated disease models by knock-down of either TGM1 or ALOXE3 in primary human keratinocytes, and using keratinocytes and fibroblasts from patients with congenital ichthyosis. The results indicate disturbed barrier function as demonstrated by increased permeation of testosterone and caffeine particularly in TGM1 knock-down models compared to control models.

Improving topical non-melanoma skin cancer treatment: In vitro efficacy of a novel guanosine-analog phosphonate.

Actinic keratosis, a frequent carcinoma in situ of non-melanoma skin cancer (NMSC), can transform into life-threatening cutaneous squamous cell carcinoma. Current treatment is limited due to low complete clearance rates and asks for novel therapeutic concepts; the novel purine nucleotide analogue OxBu may be an option. In order to enhance skin penetration, solid lipid nanoparticles (SLN, 136-156 nm) were produced with an OxBu entrapment efficiency of 96.

Cytoprotective effects of opioids on irradiated oral epithelial cells.

Oral mucositis is a common side effect of chemotherapy and radiation therapy accompanied with acute inflammation and ulceration of the oral mucosa. Opioids can improve the wound healing of dermal and oral tissue when applied locally. The aim of this study was to investigate if morphine exhibits cytoprotective effects on oral epithelial cells postirradiation.

Filaggrin deficiency leads to impaired lipid profile and altered acidification pathways in a 3D skin construct.

Mutations in the filaggrin (FLG) gene are strongly associated with common dermatological disorders such as atopic dermatitis. However, the exact underlying pathomechanism is still ambiguous. Here, we investigated the impact of FLG on skin lipid composition, organization, and skin acidification using a FLG knockdown (FLG-) skin construct.

Reconstructed skin models as emerging tools for drug absorption studies.

Introduction: As humans can come into contact with xenobiotics intentionally or accidentally, knowledge about the skin absorption of these substances is crucial and requires reliable models and test procedures. Animal experiments should be avoided whenever possible, instead of making the use of in vitro systems. Furthermore, due to limited availability of normal and especially diseased human skin, alternative test systems such as reconstructed skin models are urgently required.

Formulation development of lyophilized, long-term stable siRNA/oligoaminoamide polyplexes.

Polyplexes based on precise oligoaminoamides exhibited promising results in non-viral siRNA delivery. However, one serious limitation is insufficient stability of polyplexes in liquid, which raises the demand for lyophilized, long-term stable formulations. Two different siRNA/oligoaminoamide polyplexes were prepared.

Polyglycerol coatings of glass vials for protein resistance.

Proteins are surface active molecules which undergo non-specific adsorption when getting in contact with surfaces such as the primary packaging material. This process is critical as it may cause a loss of protein content or protein aggregation. To prevent unspecific adsorption, protein repellent coatings are of high interest.

Targeting inflammation and wound healing by opioids.

Opioid receptors are expressed on peripheral sensory nerve endings, cutaneous cells, and immune cells; and local application of opioids is used for the treatment of inflammatory pain in arthritis, burns, skin grafts, and chronic wounds. However, peripherally active opioids can also directly modulate the inflammatory process and wound healing. Here, we discuss the underlying mechanisms of opioid action and the conceivable therapeutic approaches for opioid treatment, as investigated in experimental and clinical studies.

A thermosensitive morphine-containing hydrogel for the treatment of large-scale skin wounds.

Purpose: Topically applied opioids are an option to induce efficient analgesia in patients with severe skin wounds. For ongoing pain reduction, the vehicle should provide sustained drug release in order to increase the intervals during the regular wound dressing changes. In addition, the formulation should not impair wound healing.

Surfactant free preparation of biodegradable dendritic polyglycerol nanogels by inverse nanoprecipitation for encapsulation and release of pharmaceutical biomacromolecules.

In this paper we report a novel approach to generate biodegradable polyglycerol nanogels on different length scales. We developed a mild, surfactant free inverse nanoprecipitation process to template hydrophilic polyglycerol nanoparticles. In situ crosslinking of the precipitated nanoparticles by bioorthogonal copper catalyzed click chemistry allows us to obtain size defined polyglycerol nanogels (100-1000nm).

Comparison of four different particle sizing methods for siRNA polyplex characterization.

The ability to reliably determine the size of siRNA polyplexes is the key for the rational design of particles and their formulation, as well as, their safe application in vivo. At the moment, no standard technique for size measurements is available. Each method has different underlying principles and hence may give different results.

Lyophilization of synthetic gene carriers.

Lyophilization, also known as freeze-drying, is a widely used method for stabilization, improvement of long-term storage stability, and simplification of the handling of drugs and/or carrier systems. Lyophilization is time- and energy-consuming; hence, optimized processes are required to avoid time loss and higher costs without compromising product stability. Since the last decade nonviral, synthetic carriers for gene delivery are of increasing interest.

Morphine metabolism in human skin microsomes.

For patients with severe skin wounds, topically applied morphine is an option to induce efficient analgesia due to the presence of opioid receptors in the skin. However, for topical administration it is important to know whether the substance is biotransformed in the skin as this can eventually reduce the concentration of the active agent considerably. We use skin microsomes to elucidate the impact of skin metabolism on the activity of topically applied morphine.

Morphine stimulates cell migration of oral epithelial cells by delta-opioid receptor activation.

Oral mucositis is one of the most common side effects of chemoradiation regimens and manifestation can be dose-limiting for the therapy, can impair the patient's nutritional condition and quality of life due to severe pain. The therapeutic options are limited; often only an alleviation of the symptoms such as pain reduction by using systemic opioids is possible. Stimulating opioid receptors on peripheral neurons and dermal tissue, potent analgesic effects are induced e.

Non-analgesic effects of opioids: peripheral opioid effects on inflammation and wound healing.

Opioids are the gold standard for pain treatment but systemic opioid use is accompanied by central and intestinal side effects. As opioid receptors are expressed on peripheral sensory nerve endings, cutaneous and immune cells, local opioid application is being used for pain reduction in patients with inflammatory lesions such as burns, skin grafts, arthritis, acute or chronic wounds. In addition, peripherally active opioids have anti-inflammatory effects and can modulate wound healing.

Magnetic Drug Targeting as New Therapeutic Option for the Treatment of Biomaterial Infections.

Implant-associated infections are a challenging problem in surgery. Bacteria in biofilms are difficult to treat as they are less susceptible to antibiotics or antiseptics which require high drug concentrations at the site of infection. We present a novel strategy to concentrate high antibiotic doses systemically at the target site using newly developed antibiotic-functionalized nanoparticles directed by a magnetic drug-targeting system.

No evidence of impaired gastric emptying in early Huntington's Disease.

Background: Several factors, such as dysphagia, an increased motor activity, increased metabolic rate and a hypermetabolic state have been discussed as contributing to weight loss even at the early stages of Huntington's Disease (HD). Aim of this pilot study was to investigate gastric emptying as a possible reason for weight loss in HD.

Methods: 11 HD participants at early stages of the disease and matched controls were investigated by using the well-established and non-invasive 13C-octanoate breath test.

Hallmarks of atopic skin mimicked in vitro by means of a skin disease model based on FLG knock-down.

Loss-of-function mutations in the filaggrin gene (FLG) are a strong predisposing factor for atopic dermatitis, although their relevance to the disease pathomechanism needs further elucidation. The generation of an in vitro model of atopic skin would not only permit further evaluation of the underlying pathogenetic mechanisms and the testing of new treatment options, but would also allow toxicological studies to be performed in a simple, rapid and inexpensive manner. In this study, we have knocked down FLG expression in human keratinocytes and created three-dimensional skin models, which we used to investigate the impact of FLG on epidermal maturation and on skin absorption and its response to irritation.

Deregulated ephrin-B2 signaling in mammary epithelial cells alters the stem cell compartment and interferes with the epithelial differentiation pathway.

Cancer most probably originates from stem/progenitor cells and exhibits a similar cell hierarchy as normal tissues. Moreover, there is growing evidence that only the stem cells are capable of metastasis formation. We have previously shown that overexpression of a dominant negative ephrin-B2 mutant interferes with mammary gland differentiation and confers a metastatic phenotype to NeuT-induced mammary tumors with an increase in cells with stem/progenitor characteristics.

Arginine-vasopressin directly promotes a thermogenic and pro-inflammatory adipokine expression profile in brown adipocytes.

Arginine-vasopressin (AVP) - via activation of the hypothalamic-pituitary-adrenal (HPA) axis - may play a role in the regulation of energy homeostasis and related cardiovascular complications. Brown adipose tissue (BAT) - via dissipation of energy in the form of heat - contributes to whole body energy balance. BAT expresses vasopressin receptors.

Molecular characterization and localization of the obligate endosymbiotic bacterium in the birch catkin bug Kleidocerys resedae (Heteroptera: Lygaeidae, Ischnorhynchinae).

In contrast to specific bacterial symbionts of many stinkbugs, which are harboured extracellularly in the lumina of midgut sacs or tubular outgrowths, the obligate endosymbiont of birch catkin bug Kleidocerys resedae (Heteroptera: Lygaeidae) resides in a red-coloured, raspberry-shaped mycetome, localized abdominally, close to the midgut section. Phylogenetic analysis, based on the 16S rRNA gene and the groEL (chaperonin) gene, showed that the bacteria belong to the gamma-subdivision of the Proteobacteria and revealed a phylogenetic relationship with bacterial endosymbionts of Wigglesworthia glossinidia, the primary symbiont of tse-tse fly Glossina brevipalpis. Furthermore, RFLP analysis and sequencing revealed that K.

SLN for topical application in skin diseases--characterization of drug-carrier and carrier-target interactions.

The modes of drug-particle interactions considerably influence drug delivery by nanoparticulate carrier systems and drug penetration into the skin. The exact mechanism of the drug loading and its release are still ambiguous. Therefore, the loading process, the interaction of the agent and the lipid matrix of solid lipid nanoparticles (SLNs) as well as the uptake of the loaded agent by skin lipids were analysed by electron spin resonance (ESR) and parelectric spectroscopy (PS) using spin probes (TEMPO, TEMPOL, and CAT-1) as model drugs differing in their lipophilicity.