Hermann Luebbert

Hermann Luebbert
Ruhr-Universität Bochum | RUB · Abteilung Tierphysiologie

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154
Publications
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Publications

Publications (154)
Article
Full-text available
Background The most effective treatment modality for actinic keratosis (AK) is photodynamic therapy (PDT). Major obstacles of PDT are the need of a special illumination device and pain accompanying the illumination. These issues may be overcome by replacing an artificial high‐power light source with natural daylight for more extended illumination a...
Article
Full-text available
Background: Basal cell carcinoma (BCC) represents the most common non-melanoma skin cancer worldwide affecting mainly adult, fair-skinned individuals. The WHO distinguishes aggressive and non-aggressive forms of which prototypical variants of the latter are primary nodular and superficial BCC. Objectives: To demonstrate non-inferiority of BF-200...
Article
Full-text available
Background: Topical photodynamic therapy (PDT) is a highly effective therapy especially for extended cancerized fields of the skin. Whenever extended fields are treated pain management is advisable. Light source mediated pain management can be performed by reducing fluence rates, as long as this does not compromise efficacy. Methods: Two squamou...
Article
Full-text available
Background: Non-melanoma skin cancer (NMSC) and actinic keratosis (AK) are very common among fair-skinned individuals. A disease continuum from AK to squamous cell carcinoma (SCC) has been frequently postulated. AK and NMSC may influence quality of life (QL) of patients, and it can be suspected that disease progression entails a QL reduction. The...
Poster
Full-text available
A conference poster on Photodynamic Therapy for Actinic Keratosis and Field Cancerization Using BF-200 ALA: Results of Pivotal Phase III Trials and Follow-Up
Presentation
A presentation on a nanoemulsion based drug delivery system for PDT: Development and clinical application of BF-200 ALA
Article
Studies within the last decade have localized the functional expression of olfactory receptors (ORs) to cells outside of the olfactory epithelium. In human hepatocarcinoma and prostate cancer cells, the activation of ORs by odors modulates elementary physiological processes and leads to an inhibitory effect on proliferation. Cells of the respirator...
Article
Cells of the renal tubule system are in direct contact with compounds dissolved in the urine, such as short chain fatty acids (SCFA). Murine OR78, a member of the olfactory receptor (OR) family, is involved in SCFA-related regulation of renal blood pressure in mice. It is still unclear whether OR signaling has an impact on human renal physiology. I...
Article
Full-text available
Pathophysiological mechanisms in human airway smooth muscle cells (HASMCs) significantly contribute to the progression of chronic inflammatory airway diseases with limited therapeutic options, such as severe asthma and COPD. These abnormalities include the contractility and hyperproduction of inflammatory proteins. To develop therapeutic strategies...
Article
Full-text available
Background: Multiple actinic keratosis (AK) lesions may arise from the cancerization of large, sun-damaged skin areas. Although photodynamic therapy (PDT) is considered the most effective therapeutic option, the efficacy and safety of field treatment of multiple AK lesions with PDT has never before been tested in a pivotal trial. Objectives: To...
Article
Full-text available
Migraine animal models generally mimic the onset of attacks and acute treatment processes. A guinea pig model used the application of meta-chlorophenylpiperazine (mCPP) to trigger immediate dural plasma protein extravasation (PPE) mediated by 5-HT2B receptors. This model has predictive value for antimigraine drugs but cannot explain the delayed ons...
Article
Full-text available
Mutations in the PARK2 gene are associated with an autosomal recessive form of juvenile parkinsonism (AR-JP). These mutations affect parkin solubility and impair its E3 ligase activity, leading to a toxic accumulation of proteins within susceptible neurons that results in a slow but progressive neuronal degeneration and cell death. Here, we report...
Article
Full-text available
Various genetic or toxin-induced mouse models are frequently used for investigation of early PD pathology. Although olfactory impairment is known to precede motor symptoms by years, it is not known whether it is caused by impairments in the brain, the olfactory epithelium, or both. In this study, we investigated the olfactory function in three gene...
Poster
A poster on in vitro and in vivo Analyses of the epidermal Penetration Behavior of Ameluz (R)
Article
Full-text available
LED illumination systems were found to be more efficacious than broad spectrum lamps in recent phase III trials on photodynamic treatment of actinic keratosis. However, a detailed comparison of the light doses emitted at the appropriate spectral range and its correlation to photodynamic effects is thus far not available for the most frequently used...
Article
Full-text available
Migraine attacks originate in the meninges which are densely innervated by trigeminal nerve fibers. Stimulated endothelial cells of dural blood vessels secrete nitric oxide, where neuropeptides are released from trigeminal nerve fibers. This, in turn, leads to meningeal Plasma Protein Extravasation (PPE), serving as an established indicator for mig...
Article
Full-text available
Neurogenic inflammation occurring in migraine may be associated with plasma protein extravasation (PPE) and vasodilation of dural blood vessels. 5-HT2B receptors may be involved in the onset of migraine attacks, in which receptor activation may induce increased synthesis of nitric oxide and, subsequently, the release of vasoactive CGRP from trigemi...
Article
Full-text available
In photodynamic therapy (PDT) of neoplastic skin lesions, both ALA and MAL penetrate skin cells and serve as precursors in the synthesis of the photosensitizer, protoporphyrin IX (PpIX), in tumor cells. There has been a long debate on the differences between ALA and MAL regarding their clinical efficacy, adverse effects and molecular mechanisms und...
Article
Full-text available
Summary Background Two phase III trials of photodynamic therapy (PDT) with BF-200 ALA, a recently approved nanoemulsion formulation of 5-aminolaevulinic acid (ALA) demonstrated high clearance rates in mild-to-moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total...
Article
Full-text available
Photodynamic therapy is widely used in the treatment of superficial skin cancers. 5-Aminolevulinic acid (ALA) and its methylated form, methyl-ALA (MAL), are frequently used as precursors to photosensitizing substances. Nevertheless, the mechanism of the uptake of ALA and MAL in keratinocytes and of their skin penetration is still controversial. Sin...
Article
Full-text available
Application of δ-aminolevulinic acid (ALA) or its methyl ester (MAL) onto cutaneous tumours increases intracellular Protoporphyrin IX (PpIX), serving as photosensitizer in photodynamic therapy (PDT). While PDT is highly effective as treatment of neoplastic skin lesions, it may induce severe pain in some patients. Here, we investigated ALA and MAL u...
Article
Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) or its methylester [methyl-5-aminolaevulinate (MAL) or 5-amino-4-oxopentanoate] was recently ranked as first-line therapy for the treatment of actinic keratosis (AK) and is an accepted therapeutic option for the treatment of neoplastic skin diseases. BF-200 ALA (Biofrontera Bioscience Gmb...
Article
The histaminergic neurons of the posterior hypothalamus (tuberomamillary nucleus-TMN) control wakefulness, and their silencing through activation of GABA(A) receptors (GABA(A)R) induces sleep and is thought to mediate sedation under propofol anaesthesia. We have previously shown that the β1 subunit preferring fragrant dioxane derivatives (FDD) are...
Article
We recently described mitochondrial pathology in neurons of transgenic mice with genes associated with Parkinson's disease (PD). Now we describe severe mitochondrial damage in glial cells of the mesencephalon in mice carrying a targeted deletion of parkin (PaKO) or overexpressing doubly mutated human alpha-synuclein (asyn). The number of mitochondr...
Article
Full-text available
Parkinson's disease (PD) is a common neurodegenerative disease that involves the deterioration of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD remains poorly understood, recent genetic, postmortem, and experimental evidence shows that abnormal protein accumulation and subsequent aggregate formation are pro...
Article
Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) provides a therapeutic option for the treatment of actinic keratosis (AK). Different strategies are applied to overcome the chemical instability of ALA in solution and to improve skin penetration. A new stable nanoemulsion-based ALA formulation, BF-200 ALA, is currently in clinical develo...
Article
Full-text available
Nineteen GABAA receptor (GABAAR) subunits are known in mammals with only a restricted number of functionally identified native combinations. The physiological role of β1-subunit-containing GABAARs is unknown. Here we report the discovery of a new structural class of GABAAR positive modulators with unique β1-subunit selectivity: fragrant dioxane der...
Article
Full-text available
Accumulation of α-synuclein is observed in neurodegenerative diseases like Parkinson's disease and Multiple System Atrophy. In previous studies with transgenic C57BL/6 mice overexpressing α-synuclein carrying the mutations A53T and A30P found in Parkinson's disease or with a parkin-null background, we reported severe mitochondrial impairments in ne...
Article
Please cite this paper as: Upregulation of cathepsin S in psoriatic keratinocytes. Experimental Dermatology 2010; 19: e80–e88. Abstract: Cathepsin S (CATS) is a cysteine protease, well known for its role in MHC class II-mediated antigen presentation and extracellular matrix degradation. Disturbance of the expression or metabolism of this protease i...
Article
Activated microglia release inflammatory mediators that display either beneficial or harmful effects on neuronal survival and signaling. In the present study we demonstrate that exposure to lipopolysaccharide leads to an increase in the lysosomal cysteine proteases, cathepsin B, K, S, and X, in culture supernatants of the microglia cell line BV-2....
Article
Full-text available
Cannabinoid receptor (CB) agonists are known to attenuate allodynia in a range of pain models, but their long-term effects and their mechanisms of action are controversial. The present study compares the antiallodynic effects of long-term treatment with a mixed CB1/CB2 (WIN55,212-2) and a selective CB2 (GW405833) cannabinoid receptor agonist and co...
Article
Parkinson's disease (PD) is characterized by the deterioration of dopaminergic neurons in the pars compacta of substantia nigra and the formation of intraneuronal protein inclusions. The etiology of PD is not known, but the recent identification of several mutation genes in familial PD has provided a rich understanding of the molecular mechanisms o...
Article
Cathepsins have long been regarded enzymes that are primarily involved in general protein turnover within lysosomes. However, more recently, their differential cell and tissue distributions suggest that at least some of them participate in specific cellular processes. Cathepsin S (CATS) is mainly expressed in cells of mononuclear phagocytotic origi...
Data
Full-text available
Upregulation of cathepsin protein levels after L5T. Western blot analyses of CATX and CATS proform expression in the spinal cords of sham (n = 5) and L5T (n = 5) operated rats at 8 d after injury. Cervical, thoracic and lumbar segments were analyzed. Each band represents a single animal. C, cervical; T, thoracic; L, lumbar.
Data
Full-text available
Quantification of Western blot analyses. Quantification of Western blot analyses of CATX and CATS proform expression in the spinal cord of L5T (n = 4) and sham operated animals (n = 4) (repetition of the experiment #1 – shown in the paper). Expression levels were normalized relative to the corresponding α-tubulin band. Similar to experiment #1 – th...
Article
Rotigotine (Neupro) is a non-ergoline dopamine agonist developed for the once daily treatment of Parkinson's disease (PD) using a transdermal delivery system (patch) which provides patients with the drug continuously over 24 h. To fully understand the pharmacological actions of rotigotine, the present study determined its extended receptor profile....
Article
Tech is a RhoA guanine nucleotide exchange factor (GEF) that is highly enriched in hippocampal and cortical neurons. To help define its function, we have conducted studies aimed at identifying partner proteins that bind to its C-terminal PDZ ligand motif. Yeast two hybrid studies using the Tech C-terminal segment as bait identified MUPP1, a protein...
Article
Dopamine agonists used to manage Parkinsonian motor symptoms have been suggested to be neuroprotective. The study was designed to assess the neuroprotective potential of the D(3)/D(2)/D(1) dopamine receptor agonist rotigotine in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned (MPTP) mouse model of Parkinson's disease by measuring me...
Article
Full-text available
Ample evidence suggests a substantial contribution of cellular and molecular changes in the spinal cord to the induction and persistence of chronic neuropathic pain conditions. While for a long time, proteases were mainly considered as protein degrading enzymes, they are now receiving growing interest as signalling molecules in the pain pathology....
Article
Full-text available
Mutations in the parkin gene are the major cause of early-onset familial Parkinson's disease (PD). We previously reported the generation and analysis of a knockout mouse carrying a deletion of exon 3 in the parkin gene. F1 hybrid pa+/- mice were backcrossed to wild-type C57Bl/6 for three more generations to establish a pa-/-(F4) mouse line. The app...
Article
Full-text available
Mutations in the gene encoding alpha-synuclein (asyn) causes autosomal-dominant, in the parkin gene autosomal-recessive forms of Parkinson's disease (PD). The pathophysiology of PD is poorly understood, even though published evidence suggests a role for mitochondria in the pathogenesis. To gain insight into the influence of asyn and parkin on mitoc...
Article
Increased inflammatory activity accompanies normal brain aging. Whereas local glial cell activation, upregulation of cytokines and transcriptional alterations of inflammatory factors are well-documented components of this complex process, it is unclear whether blood-derived leukocytes also contribute to the age-related changes. The present study of...
Article
Increasing evidence of a fundamental influence of cathepsins on inflammation has drawn interest in a thorough understanding of their role in physiological and pathological processes. Even though the number of identified cathepsins has more than doubled in the last years, information about their expression, regulation and function in the brain is st...
Article
Transgenic mice expressing a mutated human Cu/Zn superoxide dismutase (SOD1) gene develop a motor neuron disease similar to familial amyotrophic lateral sclerosis (FALS). While the histopathology and the inflammatory reactions in the spinal cord of these mice are well described, their spatiotemporal extension into brain areas and the relationship b...
Article
Serum and glucocorticoid-regulated kinase 1 (sgk1) belongs to a family of serine/threonine kinases that is under acute transcriptional control by serum and glucocorticoids. An expanding set of receptors and cellular stress pathways has been shown to enhance sgk1 expression, which is implicated in the regulation of ion channel conductance, cell volu...
Article
Recessively inherited mutations in DJ-1 have recently been linked to familial forms of parkinsonism. However, the regional and cellular expression of DJ-1 is largely unknown. In the present study, we mapped the distribution of DJ-1 transcript and protein by non-radioactive in situ hybridization and immunohistochemistry in adult mouse CNS. For immun...
Article
In an effort to gain deeper insight into the molecular processes underlying neurodegeneration in Parkinson's disease, we performed gene expression profiling at several early time points after MPTP-injection into old (1-year) mice. We used a PCR-based gene expression profiling method, digital expression pattern display (DEPD), a method of very high...
Article
To verify the relevance of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity in controlling breast-cancer cell growth, we have evaluated the correlation of 11beta-HSD2 expression and antiproliferative effects of glucocorticosteroids (GCs) on breast cancer cell proliferation. We cloned human 11beta-HSD2 cDNA into the expression vecto...
Article
Parkin is an E3 ubiquitin ligase causally involved in the pathogenesis of autosomal recessive juvenile parkinsonism. In this paper, we analysed the formation of alternative splice products and the spatio-temporal expression pattern of parkin during pre- and postnatal mouse development. Using RT-PCR, Northern blot, in situ hybridization, Western blo...
Article
Full-text available
Two missense mutations (A53T and A30P) in the gene encoding the presynaptic protein alpha-synuclein (asyn) are associated with rare, dominantly inherited forms of Parkinson's disease (PD) and its accumulation in Lewy bodies and Lewy neurites. As an initial step in investigating the role of asyn in the pathogenesis of PD, we have generated C57BL/6 t...
Article
Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for "very...
Article
Full-text available
Galantamine (Reminyl), an approved treatment for Alzheimer's disease (AD), is a potent allosteric potentiating ligand (APL) of human alpha 3 beta 4, alpha 4 beta 2, and alpha 6 beta 4 nicotinic receptors (nAChRs), and of the chicken/mouse chimeric alpha 7/5-hydroxytryptamine3 receptor, as was shown by whole-cell patch-clamp studies of human embryon...
Article
Localizing cell surface receptors to specific subcellular sites can be crucial for proper functioning. PDZ proteins apparently play central roles in such protein localizations. 5-HT(2C) receptors have previously been shown to interact with MUPP1, a multi PDZ domain protein, in heterologous systems and in rat choroid plexus. We now report the genera...
Article
Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Although valuable animal models have been developed, our knowledge of the aetiology and pathogenic factors implicated in PD is still insufficient to develop causal therapeutic strategies aimed at ha...
Article
St. John's wort (Hypericum perforatum L.) is widely used for the treatment of mild to moderately severe depression. However, the nature of its active principles and the exact mode of antidepressant action are still unknown. It has been suggested repeatedly in preclinical and clinical studies that the content of the acylphloroglucinol hyperforin dec...
Article
Digital expression pattern display (DEPD) is an open, automated, PCR-based system of gene expression profiling that is capable of resolving as many as 100,000 transcripts from a single brain tissue cDNA sample. It has a detection sensitivity of better than 1 in 750,000 and it can reliably detect differences in RNA expression levels of less than two...