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1.
Front Nutr ; 10: 1101479, 2023.
Article in English | MEDLINE | ID: mdl-36824169

ABSTRACT

So-called meat hybrids are a new class of products where a fraction of the meat product (e.g., 20%) is replaced with alternative protein sources, such as plant-based ones. Research suggests that these products could serve as a low-threshold offer for a specific target group that wants to cut down on meat, thereby facilitating the transition toward a more healthy and sustainable diet. Nonetheless, data demonstrate that meat hybrids with a high substantial meat substitution level often fail in the market. This study summarises findings on the physicochemical properties, sensory, and acceptance of six different meat hybrids (70% meat and 30% plant proteins) that were collected in the framework of a case study in the project AiF 196 EN. For this purpose, sensory characteristics were collected via two QDA sessions and a hedonic consumer test. Furthermore, the hybrid recipes were analysed in their proximate composition. The respective recipes varied in protein source (soybean, pumpkin, and pea) and mode of incorporation [textured vegetable protein (TVP), high moisture extrudate (HME)]. It was shown that a meat hybrid with a relatively high share of 30% plant-based proteins with peas as a protein source and TVP as a processing method can still attract consumers.

2.
J Food Sci ; 87(4): 1731-1741, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35257380

ABSTRACT

The increasing use of wet texturized plant proteins as meat substitutes requires a characterization of their functional properties, especially in terms of pH-behavior when being mixed with meat proteins to create so-called hybrid products. In this study, a minced model system containing pork meat, curing salt, and various amounts (0-100 wt%) of wet extruded proteins from pea (Pea I, II), pumpkin (Pumpkin I, II, III), and sunflower was used to evaluate the effect of mixing on pH and time-dependent pH-changes upon the addition of glucono-delta-lactone (GDL). Increasing concentrations of plant extrudates resulted in a linear increase of the initial (pH0h ), intermediate (pH6h ), and final pH48h for all samples and higher slopes at higher native pH of extrudates were found. Acidification kinetics of all samples were similar with a distinct pH-drop by 0.3 to 0.8 pH-units per wt% GDL in the first 6 h, followed by a plateau where pH remained constant. At extrudate concentrations of 5 wt% (Pea I, II, Pumpkin I, II) or 15 wt% (Pumpkin III, Sunflower), a sufficient acidification with typically used GDL-amounts ( = 1 wt%) could be achieved, while higher plant protein contents required higher GDL-concentrations in order to reach a pH value of 5.0; a common target value in dry-cured sausages. A mathematical model was proposed to correlate pH, time, acidifier, extrudate concentration, and plant protein origin, to aid in the adjustment of dry-cured hybrid meat formulations, and to describe thresholds of the feasible extrudate and acidifier concentrations. PRACTICAL APPLICATION: Despite the increasing relevance of texturized plant proteins as meat mimetics, little is known about their functional and process-related properties. This study shows that plant protein origin, the level of meat replacement, and the amount of acidifier are linked to the time-dependent pH-value on the basis of a mathematical model. This brings food developers one step closer in creating tailored formulations and estimating the effects of these novel ingredients in the final product characteristics of hybrid meats and analogues.


Subject(s)
Meat Products , Pork Meat , Red Meat , Animals , Hydrogen-Ion Concentration , Plant Proteins , Swine
3.
Food Funct ; 13(2): 944-956, 2022 Jan 24.
Article in English | MEDLINE | ID: mdl-35005757

ABSTRACT

The exchange of animal-based for plant-based proteins is becoming more and more popular due to an increasing demand for alternative and more sustainable protein sources. In this study, solubilized water- (ws) or salt-and-water (sws) meat proteins were evaluated in their pH-dependent interactions with soluble protein fractions from wheat, pumpkin, sunflower, rapeseed, or potato proteins. For this purpose, 1 : 1 (v/v) mixtures of 1.0 wt% meat (ws or sws) and plant proteins were prepared at a sodium chloride concentration of 1.8 wt% (ionic strength: 0.31 mol L-1) and adjusted to different pH-values in between 4.5-7.0. While only slight differences were found upon comparison of interactions of ws and sws batches (p > 0.05), interactions among these animal-based and soluble plant proteins took place. First, optical observations, light microscopy, and SDS-PAGE revealed increasing protein solubility with increasing pH. Second, particle size distributions (PSDs) revealed a shift towards slightly larger particle sizes e.g. at pH 5.3 and 7.0 with d4,3 of 43.2 and 21.3 µm (sws) to 45.4 and 23.9 µm (sws + potato), respectively. Furthermore, heat-induced gel formation was improved at pH > 6.0, in particular in mixtures of meat and wheat or rapeseed proteins that formed a homogenous gel structure. Based on the obtained results, protein-protein complexations mainly by electrostatic forces are suggested which occur due to various pI of meat and plant proteins e.g. pH 7.5 (wheat), 7.2 (potato), and 6.6 (rapeseed) in comparison to 5.1 (ws) and 5.6 (sws). The filamentous microstructure of some gels (soluble fraction of rapeseed, potato and wheat proteins) led to the assumption that meat proteins, mainly at pH values greater than 5.8 (optimally ≥6.5), had a structuring effect on plant proteins.


Subject(s)
Food Handling/methods , Meat Proteins/chemistry , Plant Proteins/chemistry , Animals , Electrophoresis, Polyacrylamide Gel , Hydrogen-Ion Concentration , Meat/analysis , Microscopy, Electron, Scanning , Swine
4.
J Sci Food Agric ; 102(3): 1021-1029, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34312871

ABSTRACT

BACKGROUND: The use of plant proteins as food ingredients might be limited due to the presence of foreign or 'off' flavors, which may evolve during extraction and subsequent processing. In this study, the influence of dry (TVP) and wet (WTP) texturization on characteristic volatile compounds of two different pea protein isolates was assessed using gas chromatography-mass spectrometry-olfactometry (GC-MS-O) after direct immersion stir bar sorptive extraction (DI-SBSE). RESULTS: Twenty-four odor-active compounds were found, with a prevalence of carbonyls from fat oxidation. Nine of these compounds which are also known as major (off-) flavor contributors in peas were distinctively impacted in all texturates: hexanal, nonanal, 2-undecanone, (E)-2-octenal, (E, Z)-3,5-octadiene-2-one, (E, E)-2,4-decadienal, 2-pentyl-furan, 2-pentyl-pyridine, and γ-nonalactone. For example, hexanal, a characteristic green odorant, was reduced by up to sixfold by wet texturization, from 3.29 ± 1.05% (Pea Protein I) to 0.52 ± 0.02% (Pea WTP I). Furthermore, (E,Z)-3,5-Octadiene-2-one and (E,E)-2,4-decadienal were decreased by 1.5- and 1.8-fold when Pea Protein I and Pea TVP I were compared. CONCLUSION: An overall reduction in fat oxidation products and of green and fatty odor-active compounds was observed. The results represent a first insight into the process-related modulation of pea protein (off-) flavors to broaden the applicability of pea proteins as food ingredients.


Subject(s)
Odorants/analysis , Pea Proteins/chemistry , Pea Proteins/isolation & purification , Pisum sativum/chemistry , Solid Phase Extraction/methods , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/isolation & purification , Fats/chemistry , Flavoring Agents/chemistry , Flavoring Agents/isolation & purification , Gas Chromatography-Mass Spectrometry , Oxidation-Reduction
5.
Food Res Int ; 150(Pt B): 110803, 2021 12.
Article in English | MEDLINE | ID: mdl-34863495

ABSTRACT

There is an increasing demand to develop and characterize high moisture extrudates from alternative plant proteins due to their increased use in various foods. In this study, wet texturized proteins from two pea isolates and four oilseed flours from pumpkin and sunflower were subjected to an acid titration to gain insights into their buffering capacity. Results were compared to pork meat with a special emphasis on compositional differences. Wet texturized pumpkin and sunflower proteins had the highest buffering capacity, especially in between pH7.0 and pH4.5, while pea protein extrudates and pork meat were more prone to acidification and similar in buffering capacity. A multiple linear regression model further revealed that ash and select minerals and amino acids are key influencing factors on the overall buffering capacity, while the effect of protein and non-protein nitrogen depends on the evaluated pH-regime. The obtained results underline the importance for a more in-depth physicochemical characterization of texturized plant proteins and their raw materials and suggest a need for recipe and process adjustment to achieve stable pH values.


Subject(s)
Pork Meat , Red Meat , Animals , Chemical Phenomena , Flour , Plant Proteins , Swine
6.
J Agric Food Chem ; 67(23): 6551-6558, 2019 Jun 12.
Article in English | MEDLINE | ID: mdl-31099556

ABSTRACT

Unicellular microalgae are a valuable source of macro- and micronutrients. They contain, for example, proteins that are potentially useful as new emulsifiers. The aim of this study was to investigate the emulsifying properties of a less-refined lyophilized crude water-soluble extract (WSE), obtained from the heterotrophically cultivated microalga Chlorella protothecoides. Interfacial tension measurements indicated that mainly the proteins in the extract showed interfacial activity. O/W emulsions were prepared by high-pressure homogenization (1 000 bar, 3 passes) with 5.0 wt % of oil and 2.5 wt % of protein from Chlorella protothecoides, resulting in emulsions having a volume-based mean droplet diameter of d43 ≤ 1 µm and being stable for at least 7 days. Two different stress tests showed that ( i) protein-stabilized emulsions were resistant to very high salt concentrations (up to 500 mM NaCl), and ( ii) emulsions were stable over a very broad pH range of 2-9, with only minor changes in the particle size d43 (e.g. with an increase of only 300 nm when the pH was lowered from 5 to 4) compared to whey protein-stabilized emulsions. All WSE emulsions had monomodal particle size distributions and were macro- and microscopically stable during a storage of up to 7 days. The results indicate that the WSE of Chlorella protothecoides has remarkably good emulsifying properties and might be of use as a new emulsifier in various applications in which emulsions are exposed to a broad range of ionic strengths and pH values.


Subject(s)
Chlorella/chemistry , Emulsifying Agents/chemistry , Microalgae/chemistry , Plant Extracts/chemistry , Emulsifying Agents/isolation & purification , Emulsions/chemistry , Emulsions/isolation & purification , Osmolar Concentration , Plant Extracts/isolation & purification , Water/chemistry
7.
Food Funct ; 10(2): 754-764, 2019 Feb 20.
Article in English | MEDLINE | ID: mdl-30667441

ABSTRACT

This study investigated the formation and stability of emulsions with lyophilized water-soluble protein extracts from two different microalgae species. Lyophilized soluble protein extracts from Chlorella sorokiniana and Phaeodactylum tricornutum with a protein content of 39.2 and 37.2 wt%, respectively, were used. Drop-shape analysis showed them to have considerable interfacial activity at the oil-water interface. The application in emulsions, prepared by high-pressure homogenization (1000 bar, 3 passes, 5.0 wt% oil) further revealed that a concentration of 1.0 wt% soluble protein from Chlorella sorokiniana was sufficient to manufacture an emulsion with a monomodal droplet size distribution and a small volume based mean particle diameter (d43 = 232 ± 22 nm). Emulsions remained stable throughout 7 days of storage (d43,7d = 265 ± 4 nm). In contrast, 3.7 wt% of the respective proteins from Phaeodactylum tricornutum were needed to obtain a stable emulsion (d43 = 334 ± 12 nm and d43,7d = 325 ± 8 nm). Emulsions prepared with both algae fractions showed unusually high salt stabilities up to 500 mM of sodium chloride, with no appreciable changes in volume based mean particle diameter, appearance, or microstructure. Furthermore, model emulsions with soluble lyophilized proteins from Chlorella sorokiniana had a very high stability toward changes in pH (pH ≥ 5), whereas soluble proteins of Phaeodactylum tricornutum showed only a moderate pH stability with the smallest volume based particle size at pH 7.


Subject(s)
Chlorella/chemistry , Diatoms/chemistry , Emulsifying Agents/chemistry , Microalgae/chemistry , Proteins/chemistry , Water , Chemical Fractionation , Emulsions , Hydrogen-Ion Concentration , Solubility
8.
Sensors (Basel) ; 18(2)2018 Feb 09.
Article in English | MEDLINE | ID: mdl-29425169

ABSTRACT

The monitoring of liquid-filled tubes with respect to the formation of soft deposition layers such as biofilms on the inner walls calls for non-invasive and long-term stable sensors, which can be attached to existing pipe structures. For this task a method is developed, which uses an ultrasonic clamp-on device. This method is based on the impact of such deposition layers on the propagation of circumferential guided waves on the pipe wall. Such waves are partly converted into longitudinal compressional waves in the liquid, which are back-converted to guided waves in a circular cross section of the pipe. Validating this approach, laboratory experiments with gelatin deposition layers on steel tubes exhibited a distinguishable sensitivity of both wave branches with respect to the thickness of such layers. This allows the monitoring of the layer growth.

9.
Food Res Int ; 92: 48-55, 2017 02.
Article in English | MEDLINE | ID: mdl-28290297

ABSTRACT

Antisolvent precipitation is commonly used to fabricate protein nanoparticles using a simple batch method that involves injecting a protein-solvent mixture into an antisolvent. In this study, the potential of producing core-shell protein nanoparticles by antisolvent precipitation using a continuous dual-channel microfluidization method was investigated. The solvent phase (zein in ethanol) and antisolvent phase (casein in water) were made to impinge on each other at high velocity, which generates intense shear, turbulent, and cavitation forces that ensure thorough mixing and breakup of the phases. Relatively small core-shell protein nanoparticles (d<125nm) could be produced using this method when the conditions were optimized. The mean particle diameter decreased with increasing antisolvent-to-solvent ratio, increasing homogenization pressure, increasing ethanol content in the solvent phase, and decreasing zein content in the solvent phase. Depending on the processing conditions employed, zein particles in the range of about 120nm to over 1000nm could be produced. The operating conditions were further optimized to increase the final zein concentration and decrease the organic solvent content while still obtaining small particles. The surface potential of the core-shell protein nanoparticles went from positive at low pH to negative at high pH, with a point of zero charge around pH5. Electron microscopy indicated that the protein particles formed had a roughly spherical shape. The results suggest that the dual-channel microfluidizer could be used to continuously form protein nanoparticles by antisolvent precipitation. Nevertheless, when the microfluidization method was compared with the simple batch method the size of the particles produced under similar conditions were fairly similar.


Subject(s)
Caseins/chemistry , Coated Materials, Biocompatible/chemistry , Nanoparticles/chemistry , Proteins/chemistry , Zein/chemistry , Chemical Precipitation , Hydrogen-Ion Concentration , Particle Size , Solvents , Water
10.
J Neuropathol Exp Neurol ; 70(9): 748-57, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21865883

ABSTRACT

Lyme neuroborreliosis (LNB) is the most frequent tick-borne infectious disease of the central nervous system. In acute LNB and the rare chronic state of infection, patients can experience cognitive deficits such as attention and memory disturbances. During LNB, single compounds of Borrelia burgdorferi sensu lato are released into the subarachnoid space.To investigate the pathogenesis of neurologic dysfunction in LNB, we determined that the outer surface protein C (OspC), a major virulence factor of B. burgdorferi, stimulated mouse microglial cells in a dose-dependent manner to release nitric oxide (EC50 = 0.24 mg/L) in vitro. To mimic pathophysiologic conditions of long-term release of this bacterial component in vivo, we treated C57BL/6 mice with recombinant OspC from Borrelia garinii or buffer by intraventricular infusion and tested them for behavioral deficits. After 4weeks, brains were examined by routine histology and immunohistochemistry. Assessment of spatial learning and memory of treated mice during OspC exposure did not reveal significant differences from controls. Continuous exposure to intrathecal B. burgdorferi OspC led to activation of microglia and axonal damage without demonstrable cognitive impairment in experimental mice. These results suggest that long-term intrathecal exposure to OspC resulted in axonal damage that may underlie the neurologic manifestations in chronic LNB.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Antigens, Bacterial/administration & dosage , Axons/drug effects , Bacterial Outer Membrane Proteins/administration & dosage , Lyme Disease/drug therapy , Lyme Disease/pathology , Animals , Animals, Newborn , Antigens, CD/metabolism , Apoptosis/drug effects , Borrelia burgdorferi/chemistry , Brain/cytology , Calcium-Binding Proteins/metabolism , Cells, Cultured , Chemokine CXCL13/metabolism , Disease Models, Animal , Drug Interactions , Injections, Spinal/methods , Lyme Disease/chemically induced , Lyme Disease/physiopathology , Male , Maze Learning/drug effects , Mice , Mice, Inbred C57BL , Microfilament Proteins/metabolism , Microglia/drug effects , Motor Activity/drug effects , Neurons/drug effects , Neurons/pathology , Polysaccharides/toxicity , Tumor Necrosis Factors/metabolism , Up-Regulation/drug effects
11.
IEEE Trans Pattern Anal Mach Intell ; 33(12): 2521-37, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21339526

ABSTRACT

This paper considers scalable and unobtrusive activity recognition using on-body sensing for context awareness in wearable computing. Common methods for activity recognition rely on supervised learning requiring substantial amounts of labeled training data. Obtaining accurate and detailed annotations of activities is challenging, preventing the applicability of these approaches in real-world settings. This paper proposes new annotation strategies that substantially reduce the required amount of annotation. We explore two learning schemes for activity recognition that effectively leverage such sparsely labeled data together with more easily obtainable unlabeled data. Experimental results on two public data sets indicate that both approaches obtain results close to fully supervised techniques. The proposed methods are robust to the presence of erroneous labels occurring in real-world annotation data.


Subject(s)
Activities of Daily Living , Algorithms , Monitoring, Ambulatory/statistics & numerical data , Supervised Machine Learning , Databases, Factual , Humans , Motor Activity , Support Vector Machine
12.
Immunotherapy ; 2(5): 673-84, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20874651

ABSTRACT

Severe bacterial infections such as sepsis and meningitis still kill or severely injure people despite the use of bactericidal antibiotics. Therefore, new strategies for a better therapy are needed. Activin A, a member of the TGF-ß superfamily and its binding protein follistatin (FS) are released by various cell types during acute and chronic inflammatory processes. Until now, a clear definition of conditions in which activin A exerts either its pro- or anti-inflammatory functions is lacking. The activin/FS-system participates in the fine-tuning of the host's inflammatory response upon infectious stimuli. This response is on the one hand necessary for fighting pathogens, but on the other hand can negatively affect the host. This article focuses on the role of activin A and FS in infection and after acute inflammatory stimuli. The therapeutic potentials of blocking or promoting activin actions are discussed.


Subject(s)
Activins/immunology , Bacterial Infections/therapy , Follistatin/immunology , Immunotherapy , Activins/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Bacterial Infections/immunology , Follistatin/therapeutic use , Humans , Inflammation Mediators/therapeutic use
13.
Neurosci Lett ; 482(1): 17-20, 2010 Sep 20.
Article in English | MEDLINE | ID: mdl-20599470

ABSTRACT

Stimulation of murine primary microglia with Toll-like receptor (TLR) agonists enhances their ability to phagocytose and kill bacteria. Here we show that the viral TLR3 agonist poly(I:C) stimulates the release of cyto-/chemokines and nitric oxide by microglia. Poly(I:C) increases microglial phagocytosis and intracellular killing of Escherichia coli K1, a pathogenic encapsulated bacterial strain, after 30 and 90 min of co-incubation. Stimulation with a viral epitope may strengthen the resistance of the brain to bacterial infections in vivo. Our data encourage animal experiments with poly(I:C) derivatives to assess whether this approach can increase the resistance of the CNS against bacterial infections.


Subject(s)
Antiviral Agents/immunology , Escherichia coli/immunology , Microglia/immunology , Phagocytosis/immunology , Poly I-C/immunology , Toll-Like Receptor 3/immunology , Animals , Mice , Mice, Inbred C57BL , Microglia/microbiology
14.
Mol Microbiol ; 77(1): 22-43, 2010 Jul 01.
Article in English | MEDLINE | ID: mdl-20444103

ABSTRACT

The genomic analysis of Streptococcus pneumoniae strains identified the Pneumococcal adherence and virulence factor B (PavB), whose repetitive sequences, designated Streptococcal Surface REpeats (SSURE), interact with human fibronectin. Here, we showed the gene in all tested pneumococci and identified that the observed differences in the molecular mass of PavB rely on the number of repeats, ranging from five to nine SSURE. PavB interacted with fibronectin and plasminogen in a dose-dependent manner as shown by using various SSURE peptides. In addition, we identified PavB as colonization factor. Mice infected intranasally with DeltapavB pneumococci showed significantly increased survival times compared with wild-type bacteria. Importantly, the pavB-mutant showed a delay in transmigration to the lungs as observed in real-time using bioluminescent pneumococci and decreased colonization rates in a nasopharyngeal carriage model. In co-infection experiments the wild-type out-competed the pavB-mutant and infections of epithelial cells demonstrated that PavB contributes to adherence to host cell. Blocking experiments suggested a function of PavB as adhesin, which was confirmed by direct binding of SSURE peptides to host cells. Finally, PavB may represent a new vaccine candidate as SSURE peptides reacted with human sera. Taken together, PavB is a surface-exposed adhesin, which contributes to pneumococcal colonization and infections of the respiratory airways.


Subject(s)
Adhesins, Bacterial/physiology , Bacterial Adhesion , Nasopharynx/microbiology , Pneumococcal Infections/microbiology , Respiratory System/microbiology , Streptococcus pneumoniae/pathogenicity , Virulence Factors/physiology , Adhesins, Bacterial/chemistry , Adhesins, Bacterial/genetics , Animals , Carrier State/microbiology , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Epithelial Cells/microbiology , Female , Fibronectins/metabolism , Humans , Mice , Molecular Sequence Data , Molecular Weight , Plasminogen/metabolism , Pneumonia, Pneumococcal/microbiology , Protein Binding , Repetitive Sequences, Amino Acid , Sequence Analysis, DNA , Survival Analysis , Virulence Factors/chemistry , Virulence Factors/genetics
15.
Infect Immun ; 78(2): 865-71, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19933834

ABSTRACT

Toll-like receptors (TLRs) are crucial pattern recognition receptors in innate immunity that are expressed in microglia, the resident macrophages of the brain. TLR2, -4, and -9 are important in the responses against Streptococcus pneumoniae, the most common agent causing bacterial meningitis beyond the neonatal period. Murine microglial cultures were stimulated with agonists for TLR1/2 (Pam(3)CSK(4)), TLR4 (lipopolysaccharide), and TLR9 (CpG oligodeoxynucleotide) for 24 h and then exposed to either the encapsulated D39 (serotype 2) or the nonencapsulated R6 strain of S. pneumoniae. After stimulation, the levels of interleukin-6 and CCL5 (RANTES [regulated upon activation normal T-cell expressed and secreted]) were increased, confirming microglial activation. The TLR1/2, -4, and -9 agonist-stimulated microglia ingested significantly more bacteria than unstimulated cells (P < 0.05). The presence of cytochalasin D, an inhibitor of actin polymerizaton, blocked >90% of phagocytosis. Along with an increased phagocytic activity, the intracellular bacterial killing was also increased in TLR-stimulated cells compared to unstimulated cells. Together, our data suggest that microglial stimulation by these TLRs may increase the resistance of the brain against pneumococcal infections.


Subject(s)
Microglia/immunology , Phagocytosis/immunology , Pneumococcal Infections/immunology , Toll-Like Receptors/metabolism , Animals , Cells, Cultured , Chemokines/biosynthesis , Chemokines/immunology , Mice , Microglia/metabolism , Microglia/microbiology , Microscopy, Confocal , Pneumococcal Infections/metabolism , Streptococcus pneumoniae/immunology , Toll-Like Receptors/immunology
16.
Glia ; 58(3): 367-76, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19780198

ABSTRACT

Microglia express Toll-like receptors (TLRs) that recognize invading pathogens as well as endogenous proteins such as fibronectin under nonphysiological conditions. Here, we demonstrated that fibronectin stimulates murine microglia in culture in a dose-dependent manner: microglial cells secreted proinflammatory cytokines and chemokines and increased phagocytosis of Escherichia coli DH5alpha and E. coli K1 strains. Low levels of fibronectin exerted a synergistic effect on the release of proinflammatory compounds by microglia co-stimulated with agonists for TLR1/2 (Pam(3)CSK(4)) or TLR9 (CpG DNA), but not in combination with the TLR4 agonist lipopolysaccharide (LPS). Phagocytosis of bacterial strains was moderately enhanced when microglia was co-stimulated with high concentrations of fibronectin and one pathogen-derived TLR agonist. In conclusion, fibronectin increased proinflammatory and phagocytotic functions in microglia and partially synergized with microbial TLR agonists.


Subject(s)
Central Nervous System/drug effects , Escherichia coli Infections/drug therapy , Escherichia coli Infections/metabolism , Escherichia coli/physiology , Fibronectins/metabolism , Microglia/metabolism , Phagocytosis/physiology , Animals , Cells, Cultured , Central Nervous System/immunology , Central Nervous System/microbiology , Chemokines/metabolism , Cytokines/metabolism , Dose-Response Relationship, Drug , Encephalitis/chemically induced , Encephalitis/immunology , Encephalitis/metabolism , Escherichia coli Infections/immunology , Fibronectins/pharmacology , Gliosis/chemically induced , Gliosis/immunology , Gliosis/metabolism , Immunity, Innate/drug effects , Immunity, Innate/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Microglia/drug effects , Phagocytosis/drug effects , Phagosomes/drug effects , Phagosomes/metabolism , Species Specificity , Toll-Like Receptor 1/agonists , Toll-Like Receptor 1/metabolism , Toll-Like Receptor 9/agonists , Toll-Like Receptor 9/metabolism
17.
J Neurosci Res ; 88(5): 1124-36, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19859962

ABSTRACT

Neurological symptoms of patients suffering from neurodegenerative diseases such as Alzheimer's dementia (AD), Parkinson's disease (PD), or amyotrophic lateral sclerosis (ALS) often worsen during infections. We assessed the disease-modulating effects of recurrent systemic infections with the most frequent respiratory pathogen, Streptococcus pneumoniae, on the course of AD, PD, and ALS in mouse models of these neurodegenerative diseases [transgenic Tg2576 mice, (Thy1)-[A30P]alpha SYN mice, and Tg(SOD1-G93A) mice]. Mice were repeatedly challenged intraperitoneally with live S. pneumoniae type 3 and treated with ceftriaxone for 3 days. Infection caused an increase of interleukin-6 concentrations in brain homogenates. The clinical status of (Thy1)-[A30P]alpha SYN mice and Tg(SOD1-G93A) mice was monitored by repeated assessment with a clinical score. Motor performance was controlled by the tightrope test and the rotarod test. In Tg2576 mice, spatial memory and learning deficits were assessed in the Morris water maze. In none of the three mouse models onset or course of the disease as evaluated by the clinical tests was affected by the recurrent systemic infections performed. Levels of alpha-synuclein in brains of (Thy1)-[A30P]alpha SYN mice did not differ between infected animals and control animals. Plaque sizes and concentrations of A beta 1-40 and A beta 1-42 were not significantly different in brains of infected and uninfected Tg2576 mice. In conclusion, onset and course of disease in mouse models of three common neurodegenerative disorders were not influenced by repeated systemic infections with S. pneumoniae, indicating that the effect of moderately severe acute infections on the course of neurodegenerative diseases may be less pronounced than suspected.


Subject(s)
Neurodegenerative Diseases/immunology , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/immunology , Streptococcal Infections/immunology , Streptococcus pneumoniae/immunology , Acute Disease , Alzheimer Disease/genetics , Alzheimer Disease/immunology , Alzheimer Disease/physiopathology , Amyloid beta-Peptides/metabolism , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/immunology , Amyotrophic Lateral Sclerosis/physiopathology , Animals , Anti-Bacterial Agents/pharmacology , Ceftriaxone/pharmacology , Disease Models, Animal , Disease Progression , Interleukin-6/metabolism , Maze Learning/physiology , Memory Disorders/genetics , Memory Disorders/immunology , Memory Disorders/physiopathology , Mice , Mice, Transgenic , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/physiopathology , Neuropsychological Tests , Parkinson Disease/genetics , Parkinson Disease/immunology , Parkinson Disease/physiopathology , Plaque, Amyloid/genetics , Plaque, Amyloid/immunology , Plaque, Amyloid/metabolism , Recurrence , Streptococcal Infections/complications , Up-Regulation/genetics , Up-Regulation/immunology , alpha-Synuclein/genetics
18.
J Neuropathol Exp Neurol ; 68(10): 1116-24, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19918123

ABSTRACT

Bacterial DNA contains a high frequency of unmethylated cytosine-guanine (CpG) motifs that have strong immunostimulatory properties; they are recognized by mammalian Toll-like receptor 9 (TLR9). Because accumulating data suggest that chronic inflammatory processes are involved in the pathogenesis of neurodegenerative diseases, we hypothesized that inflammatory responses stimulated by CpG DNA might contribute to neurodegeneration and brain dysfunction. To assess the effects of continuous CpG DNA exposure in the brain, C57BL/6 (n = 21) and TLR9-deficient mice (n = 15) were given intracerebroventricular infusions of CpG DNA or saline for 28 days. Spatial memory assessed weekly by Morris water maze demonstrated impairment in CpG-treated wild-type mice but not in TLR9-deficient or control-treated mice. Motor function was not affected. Immunohistochemical analysis revealed marked microglial activation and acute axonal damage surrounding the ventricles, ependymal disruption, and reactive astrogliosis within the hippocampal formation in the CpG-treated wild-type but not TLR9-deficient mice or saline-infused controls. These results suggest that the unfavorable effects of CpG DNA are dependent on TLR9 signaling and that exposure to bacterial DNA may contribute to impaired neural function, neuroinflammation, and subsequent neurodegeneration.


Subject(s)
DNA/metabolism , Encephalitis/physiopathology , Memory Disorders/physiopathology , Neuroimmunomodulation/physiology , Space Perception/physiology , Toll-Like Receptor 9/metabolism , Animals , Base Composition , Cells, Cultured , Cytosine/metabolism , DNA Methylation , Encephalitis/genetics , Guanine/metabolism , Hippocampus/physiopathology , Male , Maze Learning/physiology , Memory Disorders/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Microglia/physiology , Neuroimmunomodulation/genetics , Neurons/physiology , Toll-Like Receptor 9/genetics
19.
J Neurol Sci ; 279(1-2): 106-8, 2009 Apr 15.
Article in English | MEDLINE | ID: mdl-19187943

ABSTRACT

We report a patient with rapidly progressive bilateral total ophthalmoplegia due to bilateral cavernous sinus metastasis from gastric adenocarcinoma. Among a variety of differential diagnoses, etiology of oculomotoric disorders and ophthalmoplegia includes the affection of the cranial nerves III, IV, and VI in the cavernous sinus. Unilateral metastasis in the cavernous sinus occurs quite frequently, however, a bilateral tumor infiltration of both cavernous sinus is extremely rare. Our patient impressively demonstrates the relevance of this differential diagnosis of bilateral ophthalmoplegia. Repeated CCTs and cMRIs were required to find the diagnosis and finally start a therapy, demonstrating that even with advanced neuroradiological techniques, repetition of imaging within short intervals can be necessary to detect rapidly developing metastatic infiltrations as early as possible.


Subject(s)
Adenocarcinoma/secondary , Brain Neoplasms/complications , Brain Neoplasms/secondary , Cavernous Sinus , Ophthalmoplegia/etiology , Stomach Neoplasms/pathology , Adenocarcinoma/pathology , Brain Neoplasms/pathology , Diagnosis, Differential , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Ophthalmoplegia/pathology
20.
J Neurosci Res ; 87(8): 1877-83, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19170185

ABSTRACT

An increase in adult neurogenesis was observed after exposure to enriched environment (EE) and during reconvalescence from experimental pneumococcal meningitis. This study investigated neurogenesis and spatial learning performance 5 weeks after bacterial meningitis and exposure to EE. C57BL/6 mice were infected by intracerebral injection of Streptococcus pneumoniae and treated with ceftriaxone for 5 days. Forty-eight hours after infection, one group (n = 22) was exposed to EE and the other group (n = 23) housed under standard conditions. Another set of mice was kept under either enriched (n = 16) or standard (n = 15) conditions without bacterial meningitis. Five weeks later, the Morris water maze was performed, and neurogenesis was evaluated by means of immunohistochemistry. Mice housed in EE without prior bacterial infection displayed both increased neurogenesis and improved water maze performance in comparison with uninfected control animals. Bacterial meningitis stimulated neurogenesis in the granular cell layer of the dentate gyrus: with standard housing conditions, we observed a higher density of BrdU-immunolabeled and TUC-4-expressing cells 5 weeks after induction of bacterial meningitis than in the noninfected control group. EE did not further increase progenitor cell proliferation and neuronal differentiation in the subgranular cell layer of the dentate gyrus after bacterial meningitis in comparison with infected mice housed under standard conditions. Moreover, the Morris water maze showed no significant differences between survivors of meningitis exposed to EE and animals kept in standard housing. In summary, exposure to EE after pneumococcal meningitis did not further increase meningitis-induced neurogenesis or improve spatial learning.


Subject(s)
Brain/physiopathology , Environment, Controlled , Memory Disorders/physiopathology , Memory Disorders/therapy , Meningitis, Pneumococcal/complications , Neurogenesis/physiology , Animals , Brain/microbiology , Cell Differentiation/physiology , Cell Proliferation , Dentate Gyrus/cytology , Dentate Gyrus/physiology , Disease Models, Animal , Female , Maze Learning/physiology , Memory Disorders/microbiology , Mice , Mice, Inbred C57BL , Neuronal Plasticity/physiology , Neurons/cytology , Neurons/physiology , Orientation/physiology , Recovery of Function/physiology , Regeneration/physiology , Space Perception/physiology , Stem Cells/cytology , Stem Cells/physiology
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