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Biomedical subjects

A Ludwig

Publications and source records attributed to A Ludwig.

At least 19 recordsLinked to original sources
PubMed2006

Evolutionary pattern of the gtwin retrotransposon in the Drosophila melanogaster subgroup.

The gtwin retrotransposon was recently discovered in the Drosophila melanogaster genome and it is evolutionarily closer to gypsy endogenous retrovirus. This study has identified gtwin homologous sequences in the genome of D. simulans, D. sechellia, D. erecta and D. yakuba by performing homology searches against the public genome database of Drosophila species. The phylogenetic analyses of the gtwin env gene sequences of these species have shown some incongruities with the host species phylogeny, suggesting some horizontal transfer events for this retroelement. Moreover, we reported the existence of DNA sequences putatively encoding full-length Env proteins in the genomes of Drosophila species other than D. melanogaster. The results suggest that the gtwin element may be an infectious retrovirus able to invade the genome of new species, supporting the gtwin evolutionary picture shown in this work.

Animals↗
PubMed2006

[Extranodal follicular dendritic cell sarcoma of the tonsils].

Follicular dendritic cell (FDC) sarcoma is a rare tumor deriving from dendritic cells of the lymphoid follicle. Only a few cases of extranodal manifestation of FDC sarcoma of the head and neck have been reported. We describe the case of a 47-year-old woman with a FDC sarcoma of the left tonsil that first manifested 11 years ago. She has suffered three recurrences since this time, at continually reducing intervals. Histologically, the neoplasm consisted of an increased number of spindle-shaped cells with partly hyperchromatic nuclei. The patient underwent local tumor excisions, and then received an adjuvant chemotherapy with doxorubicin and ifosfamide when she presented with the third recurrence. The 11 year follow-up bears out a more aggressive behaviour of FDC sarcoma than first assumed. Therefore, a wide local excision, eventually combined with neck dissection in the case of recurrences, seems to be necessary.

Dendritic Cells, Follicular↗
PubMed2006

Influence of the concentrations of liposomes and a submicron emulsion on the rheological properties of a topical gel.

Two different kinds of liposomes and a submicron emulsion were added to a topical hydrogel consisting of alginates. The rheological characteristics of the gels after various dilutions were investigated. The various preparations studied exhibited a similar rheological behaviour. No important interactions were observed by mixing the hydrogel with liposomes or a submicron emulsion. The viscoelastic properties and gel state were preserved, only a decrease in consistency was measured.

Administration, Topical↗
PubMed2005

Characterization and in vivo evaluation of ocular minitablets prepared with different bioadhesive Carbopol-starch components.

The purpose of this study was to evaluate different bioadhesive ocular formulations based on drum dried waxy maize starch (DDWM), Amioca starch and Carbopol 974P. The concentrations of Carbopol 974P in the mixtures varied between 5 and 25% (w/w). The rheological properties of the non-sterilized and gamma-irradiated physical blends of Carbopol 974P with either DDWM or Amioca were compared to those of the corresponding co-spray dried Amioca starch/Carbopol powders. Higher viscosity or consistency values were measured for sterilized co-spray dried powder mixtures containing an amount of Carbopol 974P equal or above 15% (w/w) compared to the physical blends. Sustained release minitablets (2 mm, 6 mg), consisting of sodium fluorescein as model drug and the bioadhesive powders, were manufactured at a compression force of 1.25 kN. Afterwards, the tablets were sterilized with gamma-irradiation. The amount of Carbopol in the co-spray dried powder mixtures on the one hand and gamma-irradiation on the other hand had no significant influence on the crushing strength and friability of the minitablets evaluated. However, these two factors affected the in vitro release properties of the minitablets. The slowest release was obtained with tablets containing 25% Carbopol 974P, which unfortunately possess mucosal irritating properties. By using co-spray dried Amioca with 15% (w/w) Carbopol 974P, a slower release can be achieved compared to the physical mixtures of DDWM or Amioca starch with Carbopol 974P. Moreover, this ocular formulation is very promising and is preferred, as it did not cause any mucosal irritation and released the model drug for at least 12 h, after application in the fornix.

Acrylic Resins↗
PubMed2005

An unusual primate locus that attracted two independent Alu insertions and facilitates their transcription.

BC200 RNA, a neuronal, small non-messenger RNA that originated from a monomeric Alu element is specific to anthropoid primates. Tarsiers lack an insert at the orthologous genomic position, whereas strepsirrhines (Lemuriformes and Lorisiformes) acquired a dimeric Alu element, independently from anthropoids. In Galago moholi, the CpG dinucleotides are conspicuously conserved, while in Eulemur coronatus a large proportion is changed, indicating that the G.moholi Alu is under purifying selection and might be transcribed. Indeed, Northern blot analysis of total brain RNA from G.moholi with a specific probe revealed a prominent signal. In contrast, a corresponding signal was absent from brain RNA from E.coronatus. Isolation and sequence analysis of additional strepsirrhine loci confirmed the differential sequence conservation including CpG patterns of the orthologous dimeric Alu elements in Lorisiformes and Lemuriformes. Interestingly, all examined Alu elements from Lorisiformes were transcribed, while all from Lemuriformes were silent when transiently transfected into HeLa cells. Upstream sequences, especially those between the transcriptional start site and -22 upstream, were important for basal transcriptional activity. Thus, the BC200 RNA gene locus attracted two independent Alu insertions during its evolutionary history and provided upstream promoter elements required for their transcription.

5' Flanking Region↗
PubMed2005

Fast modulation of heat-activated ionic current by proinflammatory interleukin 6 in rat sensory neurons.

The pro-inflammatory cytokine interleukin-6 (IL-6) together with its soluble receptor (sIL-6R) induces and maintains thermal hyperalgesia. It facilitates the heat-induced release of calcitonin gene-related peptide from rat cutaneous nociceptors in vivo and in vitro. Here we report that exposure of nociceptive neurons to the IL-6-sIL-6R complex or the gp130-stimulating designer IL-6-sIL-6R fusion protein Hyper-IL-6 (HIL-6) resulted in a potentiation of heat-activated inward currents (I(heat)) and a shift of activation thresholds towards lower temperatures without affecting intracellular calcium levels. The Janus tyrosine kinase inhibitor AG490, the selective protein kinase C (PKC) inhibitor, bisindolylmaleimide 1 (BIM1), as well as rottlerin, a selective blocker of the PKCdelta isoform, but not the cyclooxygenase inhibitor indomethacin, effectively reduced the effect. Reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization revealed expression of mRNA for the signal-transducing beta subunit of the receptor gp130 in neuronal somata, rather than satellite cells in rat dorsal root ganglia. Together, the results suggest that IL-6-sIL-6R acts directly on sensory neurons. It increases their susceptibility to noxious heat via the gp130/Jak/PKCdelta signalling pathway.

Acetophenones↗
PubMed2005

Matrix metalloproteinase 19 processes the laminin 5 gamma 2 chain and induces epithelial cell migration.

In this study we analyzed the proteolytic activity of MMP-19 and its impact on keratinocyte migration. In the HaCaT keratinocyte cell line overexpressing wild-type MMP-19 (HaCaT-WT), transmigration through fibrin and type IV collagen matrices was significantly increased compared to cells harboring a catalytically inactive mutant (HaCaT-EA). Studying the expression of MMP-19 in early stages of squamous cell cancer (SCC), we found co-localization of MMP-19 and laminin 5 at the invading tumor front but not in suprabasal epidermis of the tumor. Examination of laminin 5 processing revealed increased processing of the gamma2 chain in the medium and matrix of HaCaT-WT cells and degradation by recombinant human MMP-19 to 105-kDa and 80-kDa fragments. Parental HaCaT grown on the matrix of HaCaT-WT and HaCaT-EA cells displayed differential tyrosine phosphorylation. Using integrin blocking and stimulating antibodies we could attribute these differences to a shift from beta4-integrin-dependent signaling on the HaCaT-EA matrix toward alpha3-integrin-dependent signaling on the HaCaT-WT matrix. As a consequence, parental HaCaT showed increased migration on the matrix of HaCaT-WT cells. These data suggest that the MMP-19-dependent processing of the gamma2 chains leads to the integrin switch favoring epithelial migration and that MMP-19 actively participates in the early stages of SCC invasion.

Cell Movement↗
PubMed2005

Fungal isolation and identification in 21 cases of guttural pouch mycosis in horses (1998-2002).

This aetiological study of guttural pouch mycosis (GPM) in the horse was based on the retrospective study of 21 horses brought into the National Veterinary School of Lyon (France) between 1998 and 2002. Biopsies were taken from the lesions caused by GPM during endoscopic examination. In 87% of the cases, direct examination gave positive results, whereas 43% of the cultures were found to be negative. The main fungi observed were Aspergillus fumigatus (in three cases), A. versicolor (in two cases, together with other fungi), and A. nidulans and A. niger (one case each). In six cases, the Aspergillus species could not be identified. In two cases, cleistothecia and/or Hulle cells were observed. In three cases, fungi other than Aspergillus were seen, mixed or not with Aspergillus. These results underline the importance of Aspergillus fumigatus in the development of GPM in horses.

Animals↗
PubMed2005

Variability and evolution of bovine beta-defensin genes.

Defensins comprise an important family of antimicrobial peptides. Among vertebrates numerous defensin genes have been detected, but their evolutionary background is still discussed. We investigated the molecular evolution of bovine defensins via screening of different bovine species including the extinct ancestor of domestic cattle (Bos primigenius) for beta-defensin encoding genes. We detected a large variability of new defensin encoding sequences similar to previously published bovine neutrophil beta-defensin (bnbd), neutrophil beta-defensin 12 (nbd12), enteric beta-defensin (ebd), lingual antimicrobial peptide (lap), and tracheal antimicrobial peptide (tap). Our data suggest that variants of the same so-called subfamily (tap, lap, ebd, and nbd12) each share a common ancestry independent of their species origin, implicating several duplication events of tap, lap, ebd, and nbd12 before the different bovine lineages diverged. Variants of bovine neutrophil beta-defensins bnbd5 and bnbd9 were detected exclusively in domestic cattle and aurochs. Values of synonymous and nonsynonymous substitutions demonstrated lap, bnbd5, bnbd9 and nbd12 evolving under positive selection, whereas amino-acid altering substitutions among variants of ebd and tap are purified. Comparison of the amino-acid sequences with available structures of human and murine defensins suggested conservation of the typical secondary elements of defensins in the absence of high sequence similarity.

Animals↗
PubMed2005

The effect of freeze-drying with different cryoprotectants and gamma-irradiation sterilization on the characteristics of ciprofloxacin HCl-loaded poly(D,L-lactide-glycolide) nanoparticles.

In the present study, the influence of freeze-drying with several cryoprotective agents and gamma (gamma)-irradiation sterilization on the physicochemical characteristics of ciprofloxacin HCl-loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles was evaluated. Nanoparticles were prepared by W/O/W emulsification solvent evaporation followed by high-pressure homogenization. They were freeze-dried in the presence of 5.0% (w/v) mannitol, trehalose or glucose, with 5.0% (w/v) or 15.0% (w/v) dextran as cryoprotectants. The nanoparticles were irradiated at a dose of 25 kGy using a 60Co source. The following physicochemical properties of the formulations were investigated: the ratio of particle size before (initial) and after freeze-drying, the ease of reconstitution of the nanoparticle suspensions and the drug-release profiles of irradiated and non-irradiated nanoparticles. The antibacterial activity against Pseudomonas aeruginosa was measured. The freeze-drying process induced a significant increase in particle size when no cryoprotectant was employed. Similar results were observed when cryoprotectants were added to the formulation. Only when mannitol was used was no significant size increase measured. Moreover, for formulations with dextran, reconstitution after freeze-drying was difficult by manual agitation and particle size could not be determined because of aggregation. After gamma-sterilization no significant difference in mean particle size was observed, but reconstitution was more difficult and drug release was influenced negatively. Ciprofloxacin HCl incorporated in the nanoparticles was still effective against the micro-organism selected after freeze-drying and gamma-sterilization.

Anti-Bacterial Agents↗
PubMed2005

Rheological evaluation of dispersions, prepared with different non- and gamma-irradiated bioadhesive cospray dried powder mixtures.

Various polymer mixtures were used to prepare gels: native drum dried waxy maize starch, Amioca starch, Carbopol 974P NF and powder mixtures obtained by cospray drying Amioca starch and Carbopol 974P NF, and by blending Carbopol 974P NF with Amioca starch or drum dried waxy maize starch. Oscillatory rheology was employed to investigate the influence of gamma-irradiation, but also of the different compositions (i.e. Carbopol 974P NF varied from 5 to 25% w/w in the powder mixtures tested) and the preparation procedures of the powder mixtures on the viscoelastic properties of the polymer dispersions. The rheological data showed that gamma-irradiation has a significant influence on the rheological behaviour of the polymers dispersed. More elastic properties were obtained when the concentration of Carbopol 974P NF was increased. The dispersions containing at least an amount of 15% Carbopol 974P NF (w/w) are mainly elastic. Contrary to cospray drying the powders, blending the powders leads to higher elastic and gel properties of the dispersed polymers.

Acrylic Resins↗
PubMed2004

Effect of different sterilisation methods on the properties of bioadhesive powders and ocular minitablets, and clinical evaluation.

The purpose of this study was to evaluate the influence of gamma-irradiation and dry heat sterilisation on the properties of a bioadhesive powder mixture containing ciprofloxacin and its corresponding ocular minitablets. The molecular weight characteristics of drum dried waxy maize starch (DDWM), employed as major component of the bioadhesive formulation, the decay kinetics of radicals, the rheological properties of the bioadhesive polymers and the microbial activity of ciprofloxacin were studied. The influence of the different sterilisation methods on the characteristics of the ocular minitablets was investigated by measuring the crushing strength, the friability, and the in vitro release of ciprofloxacin from the minitablets. Finally, the clinical value of the selected sterilised minitablets was evaluated in seven healthy volunteers. Both sterilisation methods similarly affected the properties of the bioadhesive formulation by inducing stable radicals and decreasing the molecular weight of DDWM, although no changes in the microbiological activity of ciprofloxacin were measured. An obvious influence of both sterilisation methods was observed in the in vitro release study. The crushing strength and friability of the minitablets were not significantly influenced by gamma-irradiation. Based on these data, gamma-irradiation was more adequate as sterilisation method for the bioadhesive ocular minitablets than dry heat sterilisation, because it affected the least the physical properties of the minitablets. Therefore, the gamma-sterilised minitablets were selected for an in vivo evaluation in seven volunteers. The concentration of ciprofloxacin in the tear film remained above its MIC value for the most common ocular pathogens for at least 8 h. Consequently, the gamma-irradiated minitablets containing ciprofloxacin can be considered as a promising formulation to treat bacterial keratitis and conjunctivitis.

Adhesives↗
PubMed2004

Preparation and evaluation of drug-loaded gelatin nanoparticles for topical ophthalmic use.

Gelatin nanoparticles encapsulating pilocarpine HCl or hydrocortisone as model drugs were produced using a desolvation method. The influence of a number of preparation parameters on the particle properties was investigated. For the pilocarpine HCl-loaded spheres, an influence of the pH during particle preparation on the size was observed. Slightly negative zeta potential values were measured for all samples. In the case of pilocarpine HCl-loaded spheres, no influence of the gelatin type or the pH level was observed, which could be attributed to the shielding effect of ions present in the dispersion medium. When hydrocortisone was entrapped, a difference in zeta potential value between gelatin type A and gelatin type B particles was measured. A high pilocarpine HCl entrapment was established. Hydrocortisone was complexed with cyclodextrins in order to increase its aqueous solubility. The drug encapsulation was lower than in the case of pilocarpine HCl, but still amounted to approximately 30-40%. Compared to the aqueous drug solutions, a sustained release for both drugs was observed. The release kinetics of pilocarpine HCl are close to zero order, and no significant differences were measured between the various preparations. In the case of hydrocortisone, the release data suggests a difference in release rate depending on the type of cyclodextrin employed.

Administration, Topical↗
PubMed2004

Rheological evaluation of the influence of sterilisation on ocular gels using an experimental design.

Different rheological characterisation methods are employed to investigate the influence of the sterilisation method (autoclaving), the polymer concentration (0.50, 0.75 and 1.00%) and the dispersing medium (i.e. isotonic phosphate buffer and mannitol solution) on Carbopol 974 P NF dispersions, used as ocular gels. The evaluation of the different polyacrylic acid-based dispersions was performed using flow and oscillatory shear measurements, and herewith an experimental design was set up. The rheological data show that the choice of the dispersing medium has a significant influence on the rheological behaviour of the ocular gels prepared. The dispersions in mannitol exhibit higher elastic properties than those made in the phosphate buffer solution (PBS). Sterilisation increases only the elastic properties of the 0.50% (w/w) Carbopol 974 P NF/PBS dispersion but has no influence on the other dispersions prepared.

Buffers↗
PubMed2003

Implementation of a practical model for light and heat distribution using laser-induced thermotherapy near to a large vessel.

This paper introduces a simulation model for light and heat transport in tissues including perfusion effects. The model enables an efficient simulation of the damaged zone induced with an optical fibre for laser interstitial thermotherapy (LITT). It is designed specially for, but not limited to, tissue ablation in the neck region near to vessels. We describe in detail the effects of the rise in temperature caused by the absorption of light in tissue, using the heat equation and including the cooling effects of flow in vessels and of microperfusion in tissue in order to determine the extent of thermal damage. The extent of the necrosis zone is calculated with a damage function at each point of a finite element method (FEM) mesh. The FEM mesh is implemented with FEMLAB 2.3 as an add-on for finite element modelling for Matlab 6.5. LITT for tumour ablation in liver and some other anatomical regions is a well-known and established method (Bundesärztekammer und Kassenärztliche Bundesvereinigung 2002 Assessment der Bundesärztekammer und der Kassenärztlichen Bundesvereinigung, Köln). Investigations of treatments using LITT in the neck region are still in progress. We propose a refined model to validate the LITT method in the future in another anatomic region, e.g., in the highly sensitive region of the neck. Our calculations show that in order to induce a lesion with a maximum diameter of about 1 cm near to a large vessel, an application time between 3 and 4 min is needed using a laser power of about 10 W with a Nd:YAG 1064 nm radiation wavelength.

Body Temperature↗