A5103206642- Phosphodiesterase function and regulation
- Asthma and respiratory diseases
- Mast cells and histamine
- Phenothiazines and Benzothiazines Synthesis and Activities
- Receptor Mechanisms and Signaling
- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Synthesis and Catalytic Reactions
- Respiratory and Cough-Related Research
- Adenosine and Purinergic Signaling
- Pharmacological Receptor Mechanisms and Effects
- Muscle metabolism and nutrition
- Synthesis and Biological Evaluation
- Renin-Angiotensin System Studies
- Pharmaceutical studies and practices
- Antimicrobial agents and applications
- Blood Coagulation and Thrombosis Mechanisms
- Immune Cell Function and Interaction
- Wound Healing and Treatments
- Biochemical Acid Research Studies
- Coenzyme Q10 studies and effects
- Complement system in diseases
- Pulmonary Hypertension Research and Treatments
- Medicinal plant effects and applications
- Malaria Research and Control
Takeda (Switzerland)
2016
Humboldt-Universität zu Berlin
2005
Charité - Universitätsmedizin Berlin
2005
Altana (Germany)
2005
University of Konstanz
1995-2004
University of Regensburg
1995-1996
University of Southampton
1995
Klinikum Konstanz
1995
LungenClinic Grosshansdorf
1993-1994
The effects of the nonselective phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX) and selective PDE inhibitors motapizone (type III), rolipram IV), zardaverine III/IV), zaprinast V I) on prostaglandin F2 alpha (PFG2 alpha)-induced tone in human pulmonary arteries was investigated. Relaxation achieved by IBMX [concentration eliciting 50% maximum response (EC50): 11.3 microM, n = 10], (EC50:3.0 7), (EC50: 3.2 9), 31.8 6), whereas almost ineffective. combination (10 microM)...
The pleiotropic cytokine tumor necrosis factor-alpha (TNF-alpha) and thrombin lead to increased endothelial permeability in sepsis. Numerous studies demonstrated the significance of intracellular cyclic nucleotides for maintenance barrier function. Actions adenosine monophosphate (cAMP) guanosine (cGMP) are terminated by distinct nucleotide phosphodiesterases (PDEs). We hypothesized that TNF-alpha could regulate PDE activity cells, thereby impairing In cultured human umbilical vein cells...
The development of drugs for neglected infectious diseases often uses parasite-specific enzymes as targets. We here demonstrate that parasite with highly conserved human homologs may represent a promising reservoir new potential drug cyclic nucleotide-specific phosphodiesterases (PDEs) Trypanosoma brucei, causative agent the fatal sleeping sickness, are essential parasite. well-established describe what is to our knowledge first pharmacological validation trypanosomal PDEs High-throughput...
The effects of the nonselective phosphodiesterase (PDE)-inhibitor 3-isobutyl-1-methylxanthine (IBMX) and selective PDE inhibitors SKF 94120 (type III), rolipram IV), zardaverine III/IV), zaprinast V) on inherent tone in human airways were investigated. Substantial relaxation was achieved by IBMX [concentration eliciting 50% maximum response (EC50): 2.9 microM, n = 14] (EC50: 1.4 15); almost ineffective. Zardaverine 0.31 8), combination (1 microM; EC50: 0.41 microM) effective relaxants....
The effect of non‐selective (3‐isobutyl‐1‐methylxanthine, IBMX; theophylline) and type IV‐ or III/IV‐selective (rolipram, RP 73401; zardaverine, tolafentrine) phosphodiesterase (PDE) inhibitors on human eosinophil functions was investigated. For this purpose eosinophils were purified from blood healthy donors by a magnetic cell separation (MACS) technique to purity ≥ 99%. From the stimuli investigated (complement C5a; N‐formyl‐methionyl‐leucyl‐phenylalanine, fMLP; platelet activating factor,...
Summary Background Alveolar macrophages and their precursors, the monocytes are involved in airway inflammation asthma. An increase intraceliular cAMP by PDE inhibitors is known to suppress macrophage monocyte functions. A comparison of PDE‐isoenzyine profiles human alveolar from normal atopic donors peripheral blood might form a basis differentially affect functions these cells inhibitors. Objective The study compares isoenzyme activity asthmatic monocytes. In addition, effect vitro...
Summary Background CD4 + and CD8 T‐lymphocytes are suggested to differentially affect airway inflammation in asthma. Agents which increase intracellular cAMP levels, such as PDE inhibitors, have been shown diminish lymphocyte growth differentiation, cytokine expression. Differences the isoenzyme profile between cells might form a basis modify their functions by inhibitors. Objective The study investigates compares activity profiles of human peripheral blood T‐lymphocytes. Methods were...
Trypanosoma brucei cyclic nucleotide phosphodiesterase B1 (TbrPDEB1) and TbrPDEB2 have recently been validated as new therapeutic targets for human African trypanosomiasis by both genetic pharmacological means. In this study we report the crystal structure of catalytic domain unliganded TbrPDEB1 its use in silico screening inhibitors with novel scaffolds. The shows characteristic folds PDE enzymes but also contains parasite-specific P-pocket found structures Leishmania major PDEB1 cruzi...
Lung macrophages (LMs) are critically involved in respiratory diseases. The primary objective of the present study was to determine whether or not an adenosine analog (NECA) and prostaglandin E2 (PGE2) affected interleukin (IL)-4- IL-13-induced release M2a chemokines (CCL13, CCL17, CCL18, CCL22) by human LMs. Primary isolated from resected lungs were incubated with NECA, PGE2, roflumilast, vehicle stimulated IL-4 IL-13 for 24 h. levels PGE2 culture supernatants measured using ELISAs enzyme...
We studied whether selective inhibitors of cyclic nucleotide hydrolysing phosphodiesterase (PDE) isoenzymes influence IL-1beta-induced nitric oxide (NO) release from human articular chondrocytes. In addition, the pattern PDE contributing to hydrolysis in chondrocytes was characterized. Chondrocytes were isolated osteoarthritic cartilage and cultured alginate beads. chondrocyte products (nitric prostaglandin E(2)) measured culture supernatants after 48 h incubation time. activities assessed...
Inefficient wound healing poses a global health challenge with lack of efficient treatments. Wound issues often correlate low endogenous nitric oxide (NO) levels. While exogenous delivery NO-releasing compounds represents promising therapeutic strategy, controlling the release highly reactive NO remains challenging. Phosphodiesterase 5 (PDE5) inhibitors, like sildenafil, have also been shown to promote healing. This study explores hybrid compounds, combining diazeniumdiolates...
Roflumilast is an oral, add-on option for treating patients with severe COPD and frequent exacerbations despite optimal therapy inhaled drugs. The present study focused on whether this phosphodiesterase 4 inhibitor its active metabolite roflumilast N-oxide affect the tone of human bronchial rings. We also investigated interactions between roflumilast, long-acting β2 -agonist formoterol regard to relaxation isolated rings at basal or pre-contracted histamine. Our results demonstrated first...
Abstract A series of new positive inotropic agents was synthesized with the aim combining pharmacophores imidazolone‐type phosphodiesterase (PDE) inhibitor enoximone and guanidine‐type histamine H 2 receptor agonists such as arpromidine. All compounds are para ‐substituted 4‐benzoyl‐5‐alkyl‐2‐imidazolones. agonism incorporated by p ‐(hetero)arylalkyl substituents, in particular an imidazolylpropyl guanidine group. In addition analogous ureas, cyanoguanidines, alkyl carboxylates, amides were...
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