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1.
HNO ; 67(8): 600-605, 2019 Aug.
Article in German | MEDLINE | ID: mdl-31053940

ABSTRACT

BACKGROUND: In addition to basic ophthalmologic diagnostic workup, different radiologic procedures can be performed for assessment of nasolacrimal duct obstruction. However, no gold standard imaging technique has yet been established. Using the results of the present study, the advantages of helical CT-dacryocystography (CT-DCG) are demonstrated, particularly when performed before endonasal endoscopic dacryocystorhinostomy. MATERIALS AND METHODS: In 21 patients with uni- or bilateral epiphora, 24 low-dose helical CT-DCGs were performed with non-ionic iodine-containing contrast medium and including three-dimensional reconstruction. For 8 patients, digital subtraction angiography (DSA)-DCG results were available for comparison with CT-DCG. RESULTS: Using low-dose helical CT-DCG, either the location of nasolacrimal duct pathology could be exactly identified (n = 19; stenosis presaccal n = 3, intrasaccal n = 11, postsaccal n = 5) or nasolacrimal system block could be definitively excluded as the cause of epiphora (n = 5). For imaging of the perilacrimal and periorbital bony structures, CT-DCG is significantly better than DSA-DCG. CONCLUSION: Low-dose helical CT-DCG with reconstruction of the coronal and sagittal planes represents an ideal imaging technique with low exposure for detection of nasolacrimal duct obstruction. By demonstrating all relevant anatomic landmarks for endoscopic dacryocystorhinostomy, helical CT-DCG enables head and neck surgeons to plan surgery optimally.


Subject(s)
Dacryocystorhinostomy , Lacrimal Duct Obstruction , Nasolacrimal Duct , Dacryocystorhinostomy/methods , Humans , Prospective Studies , Tomography, Spiral Computed
2.
Pneumologie ; 73(2): 81-86, 2019 Feb.
Article in German | MEDLINE | ID: mdl-30508847

ABSTRACT

Pulmonary emphysema is characterised by irreversible destruction and enlargement of alveolar structure distal to terminal bronchioles. Small conducting airways < 2 mm in diameter are the major site of chronic airway inflammation and obstruction in COPD patients. 80 - 90 % of the last generation of small conducting airways, the terminal bronchioles, are destroyed in patients with very severe COPD. Recent data showing, that small airways disease is also a pathological feature in patients with COPD GOLD stage 1 and 2. Although 40 % of terminal and 60 % of transitional bronchioles were destroyed, there was no sign for emphysema. Only a significant loss of terminal and respiratory bronchioles seems to be able to induce pulmonary emphysema and respiratory symptoms.


Subject(s)
Bronchioles/physiopathology , Lung/pathology , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Emphysema/physiopathology , Humans , Severity of Illness Index
3.
Thromb Res ; 165: 101-106, 2018 05.
Article in English | MEDLINE | ID: mdl-29627719

ABSTRACT

OBJECTIVE: Determination of lupus anticoagulants (LA) is an important, but still challenging test in the diagnosis of antiphospholipid syndrome (APS). This is especially the case in patients using one of the direct oral anticoagulants (DOACs). The aim of our study was to examine the influence of these drugs on DRVVT assays from two companies (in each case: screening test, confirming test and calculated ratio) and on aPTT and lupus-sensitive aPTT. METHODS: We used plasma samples from healthy volunteers spiked with the DOACs dabigatran, rivaroxaban and apixaban (0, 10, 30, 50, 100 ng/mL) for testing. Furthermore, samples from patients receiving a DOAC were investigated. The plasma concentrations of the DOACs were determined using ultra-performance liquid chromatography/electrospray ionization-tandem mass spectrometry (UPLC-MS/MS). RESULTS: Depending on type and concentration, all the DOACs resulted in pathological values in the DRVVT screening assays. In samples spiked with apixaban, no influence on the DRVVT normalized ratio of the two assays was observed, but 7 to 15% of samples from patients receiving apixaban displayed pathological values. In contrast, up to 71% of dabigatran-spiked samples showed normalized ratio values above the cut-off, whereas there was no influence in the patients' samples. In both spiked and patient samples containing rivaroxaban, the DRVVT assays were influenced. CONCLUSION: LA diagnostics should, under DOAC therapy, be limited to situations in which time-critical evaluation is warranted. It is crucial to take into account the finding that even samples containing DOAC concentrations below the limit of detection of the drugs may lead to false-positive DRVVT measurements.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Tests/methods , Lupus Coagulation Inhibitor/therapeutic use , Administration, Oral , Anticoagulants/pharmacology , Female , Humans , Lupus Coagulation Inhibitor/pharmacology , Male
4.
Clin Nutr ; 37(2): 494-504, 2018 04.
Article in English | MEDLINE | ID: mdl-28302406

ABSTRACT

The potential of fish or fish oil as supplier for eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) for reducing cardiovascular risk factors and supporting therapy of chronic inflammatory diseases, has been investigated intensively, but our knowledge about the physiological effects of the individual compounds EPA and DHA are limited. STUDY DESIGN: In this double-blind pilot study, thirty-eight patients with defined RA were allocated to consume foods enriched with microalgae oil from Schizochytrium sp. (2.1 g DHA/d) or sunflower oil (placebo) for 10 weeks (cross-over), maintaining the regular RA medication during the study. RESULTS: In contrast to placebo, the daily consumption of DHA led to a decline in the sum of tender and swollen joints (68/66) from 13.9 ± 7.4 to 9.9 ± 7.0 (p = 0.010), total DAS28 from 4.3 ± 1.0 to 3.9 ± 1.2 (p = 0.072), and ultrasound score (US-7) from 15.1 ± 9.5 to 12.4 ± 7.0 (p = 0.160). The consumption of placebo products caused an increase of the n-6 PUFA linoleic acid and arachidonic acid (AA) in erythrocyte lipids (EL, p < 0.05). The amount of DHA was doubled in EL of DHA-supplemented patients and the ratios of AA/EPA and AA/DHA dropped significantly. We speculate that the production of pro-inflammatory/non-resolving AA-derived eicosanoids might decrease in relation to anti-inflammatory/pro-resolving DHA- and EPA-derived lipid mediators. In fact, plasma concentrations of AA-derived thromboxane B2 and the capacity of blood to convert AA to the pro-inflammatory 5-lipoxygenase product 5-hydroxyeicosatetraenoic acid were significantly reduced, while levels of the DHA-derived maresin/resolvin precursors 14-/17-hydroxydocosahexaenoic acid significantly increased due to DHA supplementation. CONCLUSION: The study shows for the first time that supplemented microalgae DHA ameliorates disease activity in patients with RA along with a shift in the balance of AA- and DHA-derived lipid mediators towards an anti-inflammatory/pro-resolving state.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Docosahexaenoic Acids/therapeutic use , Microalgae , Plant Oils/therapeutic use , Sunflower Oil/therapeutic use , Cross-Over Studies , Double-Blind Method , Female , Germany , Humans , Male , Middle Aged , Pilot Projects , Treatment Outcome
5.
Leukemia ; 31(10): 2181-2190, 2017 10.
Article in English | MEDLINE | ID: mdl-28119525

ABSTRACT

Blinatumomab can induce a complete haematological remission in patients in 46.6% with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL) resulting in a survival benefit when compared with chemotherapy. Only bone marrow blast counts before therapy have shown a weak prediction of response. Here we investigated the role of regulatory T cells (Tregs), measured by CD4/CD25/FOXP3 expression, in predicting the outcome of immunotherapy with the CD19-directed bispecific T-cell engager construct blinatumomab. Blinatumomab responders (n=22) had an average of 4.82% Tregs (confidence interval (CI): 1.79-8.34%) in the peripheral blood, whereas non-responders (n=20) demonstrated 10.25% Tregs (CI: 3.36-65.9%). All other tested markers showed either no prediction value or an inferior prediction level including blast BM counts and the classical enzyme marker lactate dehydrogenase. With a cutoff of 8.525%, Treg enumeration can identify 100% of all blinatumomab responders and exclude 70% of the non-responders. The effect is facilitated by blinatumomab-activated Tregs, leading to interleukin-10 production, resulting in suppression of T-cell proliferation and reduced CD8-mediated lysis of ALL cells. Proliferation of patients' T cells can be restored by upfront removal of Tregs. Thus, enumeration of Treg identifies r/r ALL patients with a high response rate to blinatumomab. Therapeutic removal of Tregs may convert blinatumomab non-responders to responders.


Subject(s)
Antibodies, Bispecific/therapeutic use , Immunotherapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Salvage Therapy , T-Lymphocytes, Regulatory/immunology , Adolescent , Adult , Aged , Antibodies, Bispecific/immunology , Antigens, Differentiation, T-Lymphocyte/analysis , Cell Line, Tumor , Clinical Trials as Topic , Cytotoxicity, Immunologic , Female , Humans , Immunophenotyping , Interleukin-10/biosynthesis , Interleukin-10/genetics , Lymphocyte Activation , Lymphocyte Count , Male , Middle Aged , Prognosis , Remission Induction , T-Lymphocyte Subsets/immunology , Treatment Outcome
6.
Mol Psychiatry ; 21(12): 1752-1767, 2016 12.
Article in English | MEDLINE | ID: mdl-26809838

ABSTRACT

Recombinant human erythropoietin (EPO) improves cognitive performance in neuropsychiatric diseases ranging from schizophrenia and multiple sclerosis to major depression and bipolar disease. This consistent EPO effect on cognition is independent of its role in hematopoiesis. The cellular mechanisms of action in brain, however, have remained unclear. Here we studied healthy young mice and observed that 3-week EPO administration was associated with an increased number of pyramidal neurons and oligodendrocytes in the hippocampus of ~20%. Under constant cognitive challenge, neuron numbers remained elevated until >6 months of age. Surprisingly, this increase occurred in absence of altered cell proliferation or apoptosis. After feeding a 15N-leucine diet, we used nanoscopic secondary ion mass spectrometry, and found that in EPO-treated mice, an equivalent number of neurons was defined by elevated 15N-leucine incorporation. In EPO-treated NG2-Cre-ERT2 mice, we confirmed enhanced differentiation of preexisting oligodendrocyte precursors in the absence of elevated DNA synthesis. A corresponding analysis of the neuronal lineage awaits the identification of suitable neuronal markers. In cultured neurospheres, EPO reduced Sox9 and stimulated miR124, associated with advanced neuronal differentiation. We are discussing a resulting working model in which EPO drives the differentiation of non-dividing precursors in both (NG2+) oligodendroglial and neuronal lineages. As endogenous EPO expression is induced by brain injury, such a mechanism of adult neurogenesis may be relevant for central nervous system regeneration.


Subject(s)
Erythropoietin/metabolism , Neurogenesis/drug effects , Oligodendroglia/drug effects , Animals , Brain/metabolism , Cell Differentiation/drug effects , Cell Differentiation/physiology , Central Nervous System/metabolism , Cognition/drug effects , Hippocampus/metabolism , Hippocampus/physiology , Male , Mice , Mice, Inbred C57BL , Neurogenesis/physiology , Neurons/metabolism , Oligodendroglia/metabolism , Pyramidal Cells/drug effects , Pyramidal Cells/metabolism , Recombinant Proteins/metabolism
7.
Zentralbl Chir ; 140 Suppl 1: S16-21, 2015 Oct.
Article in German | MEDLINE | ID: mdl-25393732

ABSTRACT

Septic arthritis of the sternoclavicular joint (SCJ) is a relatively rare disease. Due to serious complications including mediastinitis and generalised sepsis early diagnosis and rapid onset of treatment are mandatory. The disease often affects immunocompromised patients, diabetics, or patients with other infectious diseases. The therapeutic options range from administration of antibiotics to extended surgery including reconstructive procedures. Apart from rare situations where conservative treatment with antibiotics is sufficient, joint resection followed by plastic surgical procedures are required. We present a retrospective analysis with data from two hospitals. From January 2008 to December 2012 23 patients with radiographically confirmed septic arthritis of various aetiology were included. Fourteen (60.8 %) male, nine (39.2 %) female patients with an average age of 60.3 ± 14.2 years (range: 23-88 years) with septic arthritis of the SCJ were treated. Seven (30.4 %) patients suffered from Diabetes mellitus, nine (39.1 %) had underlying diseases with a compromised immune system. In 14 (60.8 %) out of 23 patients a bacterial focus was detected. Only six (26 %) patients suffered from confined septic arthritis of the SCG, in 17 (73,9 %) patients osteomyelitis of the adjacent sternum, and the clavicle was present. In addition, 15 (65.2 %) patients already suffered from mediastinitis at the time of diagnosis, eight (35 %) patients even from septicaemia. In conclusion, septic arthritis requires an active surgical treatment. Limited incision of the joint and debridement alone is only successful at early stages of the disease. The treatment concept has to include the local joint and bone resection as well as complications like mediastinitis. After successful treatment of the infection, the defect of the chest wall requires secondary reconstructive surgery using a pedicled pectoralis muscle flap.


Subject(s)
Arthritis, Infectious/surgery , Rare Diseases , Sternoclavicular Joint/surgery , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Arthritis, Infectious/diagnostic imaging , Arthritis, Infectious/etiology , Clavicle/diagnostic imaging , Clavicle/surgery , Combined Modality Therapy , Early Diagnosis , Early Medical Intervention , Female , Humans , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Male , Manubrium/diagnostic imaging , Manubrium/surgery , Middle Aged , Osteomyelitis/diagnosis , Osteomyelitis/etiology , Osteomyelitis/surgery , Retrospective Studies , Sternoclavicular Joint/diagnostic imaging , Tomography, X-Ray Computed , Young Adult
8.
Andrology ; 1(6): 822-9, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23996961

ABSTRACT

Aberrant sperm DNA methylation patterns, mainly in imprinted genes, have been associated with male subfertility and oligospermia. Here, we performed a genome-wide methylation analysis in sperm samples representing a wide range of semen parameters. Sperm DNA samples of 38 males attending a fertility centre were analysed with Illumina HumanMethylation27 BeadChips, which quantify methylation of >27 000 CpG sites in cis-regulatory regions of almost 15 000 genes. In an unsupervised analysis of methylation of all analysed sites, the patient samples clustered into a major and a minor group. The major group clustered with samples from normozoospermic healthy volunteers and, thus, may more closely resemble the normal situation. When correlating the clusters with semen and clinical parameters, the sperm counts were significantly different between groups with the minor group exhibiting sperm counts in the low normal range. A linear model identified almost 3000 CpGs with significant methylation differences between groups. Functional analysis revealed a broad gain of methylation in spermatogenesis-related genes and a loss of methylation in inflammation- and immune response-related genes. Quantitative bisulfite pyrosequencing validated differential methylation in three of five significant candidate genes on the array. Collectively, we identified a subgroup of sperm samples for assisted reproduction with sperm counts in the low normal range and broad methylation changes (affecting approximately 10% of analysed CpG sites) in specific pathways, most importantly spermatogenesis-related genes. We propose that epigenetic analysis can supplement traditional semen parameters and has the potential to provide new insights into the aetiology of male subfertility.


Subject(s)
DNA Methylation , Fertility/genetics , Genes, MHC Class II , Infertility, Male/genetics , Inflammation/genetics , Spermatogenesis/genetics , CpG Islands/physiology , Fertility/immunology , Gene Ontology , Humans , Male , Reproduction/genetics , Sperm Count
9.
Water Res ; 47(3): 1433-47, 2013 Mar 01.
Article in English | MEDLINE | ID: mdl-23290913

ABSTRACT

Phosphorus retention in sediments has been estimated for three basins in Lake Simcoe, a mesotrophic lake in Ontario, Canada. Total phosphorous (TP) fractionation was used to examine the concentration of phosphorus (P) binding forms in the sediments of Cook's Bay, Kempenfelt Bay, and the Main Basin. The extended sequential extractions allowed us to differentiate between organic-, inorganic-, carbonate-bounded and redox-sensitive phosphorus. Our results showed different mechanisms of P release in each of the three investigated basins, which may be linked to their distinct loading histories, present land-uses and morphology of the sampling sites. In the deep Main Basin, where moderate changes in P loading have been induced by deforestation, sediments are not an important long-term source of diagenetically mobile P, as almost 75% of P is released within a short time scale. P release is predominantly generated by a continuous epilimnetic P flux, rather than a large inventory of temporary P stored in the sediments. Diagenesis in the upper sediment layers is fast enough to prevent a large accumulation of temporary P. In the much deeper glacially formed Kempenfelt Bay with a highly urbanized catchment, P release from the sediments is dominated by the redox-sensitive P fraction, representing up to 40% and 57% of long- and short-term sediment P release, respectively. In the shallow and agriculturally-impacted Cook's Bay, the main P binding form that can be mobilized through diagenesis is carbonate-bound P. This fraction contributes 40.1% and 37.6% to the long- and short-term P sediment release, respectively. Although different mechanisms of P release have been revealed for the three basins in Lake Simcoe, the vertical profiles indicate that the sediments throughout the system are still able to bind deposited P.


Subject(s)
Lakes , Phosphorus/chemistry , Environmental Monitoring , Geologic Sediments/chemistry
10.
Z Orthop Unfall ; 150(6): 624-6, 2012 Dec.
Article in German | MEDLINE | ID: mdl-23296558

ABSTRACT

After infection of a vascular prosthesis with generalised sepsis, a 59-year-old male patient suffered from an increasing swelling of his right sternoclavicular joint. We performed an incision and debridement of the SC joint and harvested material for microbiological diagnosis. However, we were not able to overcome the inflammation until we performed a radical resection including the medial aspect of the clavicle and parts of the manubrium followed by coverage with a pectoralis flap. The further course was uneventful with a good functional result. Reviewing data from the literature there are no unequivocal guidelines available for this rare disease. However, in most cases a radical debridement and a consecutive flap coverage are required.


Subject(s)
Arthritis, Infectious/diagnostic imaging , Arthritis, Infectious/surgery , Muscle, Skeletal/transplantation , Prosthesis-Related Infections/surgery , Sternoclavicular Joint/diagnostic imaging , Sternoclavicular Joint/surgery , Surgical Flaps , Combined Modality Therapy/methods , Humans , Male , Middle Aged , Prosthesis-Related Infections/diagnostic imaging , Radiography , Reoperation/methods , Treatment Outcome
11.
Neuroscience ; 167(3): 838-49, 2010 May 19.
Article in English | MEDLINE | ID: mdl-20188151

ABSTRACT

(R)-roscovitine (Ros) is a cyclin-dependent kinase inhibitor that also has been shown to have direct agonist and antagonist actions on Ca(v)2.1 (P/Q-type) and Ca(v) 2.2 (N-type) families of voltage-gated calcium channels. These kinase-independent effects represent a novel opportunity to advance our understanding of calcium channel function and calcium-triggered neurotransmitter release. Furthermore, such actions on calcium channels may direct the development of Ros derivatives as new therapeutic agents. We used patch clamp recordings to characterize mechanisms that underlie the agonist effects of Ros on unitary N-type calcium channel gating. We found that N-type channels normally gate with either a short or long mean open time, that Ros significantly prolonged the mean open time of the long gating component and increased the probability of observing channels that gated with a long open time, but had no effect on single channel conductance. Using Monte Carlo simulations of a single channel kinetic model and Ros interactions, we were able to reproduce our experimental results and investigate the model's microscopic dynamics. In particular, our simulations predicted that the longer open times generated by Ros were due to the appearance of a long open state combined with an increased amount of time spent in transitions between open states. Our results suggest a mechanism for agonist effects of Ros at the level of single channels, and provide a mechanistic explanation for previously reported agonist effects on whole cell calcium currents.


Subject(s)
Calcium Channels, N-Type/drug effects , Cell Membrane/drug effects , Ion Channel Gating/drug effects , Neurons/drug effects , Purines/pharmacology , Animals , Calcium Channels, N-Type/metabolism , Calcium Signaling/drug effects , Calcium Signaling/physiology , Cell Line , Cell Membrane/metabolism , Computer Simulation , Ion Channel Gating/physiology , Kinetics , Membrane Potentials/drug effects , Membrane Potentials/physiology , Monte Carlo Method , Neurons/metabolism , Patch-Clamp Techniques , Protein Kinase Inhibitors/pharmacology , Rats , Roscovitine , Synaptic Transmission/drug effects , Synaptic Transmission/physiology , Time Factors
12.
Geobiology ; 7(3): 324-47, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19476505

ABSTRACT

Calcite nucleation on the surface of cyanobacteria of the Synechococcus leopoliensis strain PCC 7942 was investigated to assess the influence of photosynthetic uptake of inorganic carbon and active ion exchange processes across the cell membrane on the nucleation and precipitation mechanisms. We performed long-term precipitation experiments at a constant CO(2) level in ambient air by adding suspensions of previously washed cyanobacteria to solutions of NaHCO(3)/CaCl(2) which were supersaturated with respect to calcite. Induction times between 4 and 110 h were measured over a range of saturation states, Omega, between 8 and 4. The kinetics of CaCO(3) nucleation was compared between experiments: (i) with ongoing photosynthesis, (ii) with cells metabolizing but not undergoing photosynthetic uptake of inorganic carbon and (iii) in darkness without photosynthesis. No significant differences were observed between the three treatments. The results reveal that under low nutrient concentrations and permanent CO(2) supply, photosynthetic uptake of inorganic carbon predominantly uses CO(2) and consequently does not directly influence the nucleation process of CaCO(3) at the surface of S. leopoliensis. Furthermore, ion exchange processes did not affect the kinetics, indicating a passive nucleation process wherein the cell surface or extracellular polymers provided preferential sites for mineral nucleation. The catalyzing effect of the cyanobacteria on calcite nucleation was equivalent to a approximately 18% reduction in the specific interfacial free energy of the calcite nuclei. This result and the ubiquitous abundance of cyanobacteria suggest that this process may have an impact on local and global carbon cycling.


Subject(s)
Calcium Carbonate/metabolism , Synechococcus/metabolism , Calcium Chloride/metabolism , Carbon Dioxide/metabolism , Darkness , Light , Sodium Bicarbonate/metabolism
13.
Sportverletz Sportschaden ; 22(3): 164-8, 2008 Sep.
Article in German | MEDLINE | ID: mdl-18814059

ABSTRACT

PROBLEMS: Soccer as a Stop-and-Go-sport goes along with a high level of physical strain on the locomotor system. Compared to similar kinds of sports, soccer is characterized by a high prevalence of overloads/injuries in the pelvic region. Since soccer frequently involves one-sided shot-training, modifications in the pelvic statics are possible. METHODS: In a pilot study including 15 football-players-FP (age 26.9 +/- 3.1 yrs; 4.4 +/- 0.4 training units/week+ 1 leaque game) the pelvic statics was measured using the 3-d-recording system CMS70 (Zebris, Germany) directly before and after a defined shot training. The positions of the right and the left posterior superior iliac spines - PSIS were compared. Additionally, the stiffness of selective muscles was analyzed. RESULTS: Before intervention the right PSIS was heightened in 8 FP. In 4 FP the pelvic statics was balanced and in 3 FP the right PSIS was abased. After the shot training, the pelvic statics was balanced in 4 FP. In contrast, 10 FP showed a higher right PSIS and 1 FP had a lower right PSIS. However, modifications of the pelvic statics were detected in all directions. DISCUSSION: Our study demonstrates modification of the pelvic statics by asymmetric soccer-specific strains, but the reactions were individually different. It is possible, that changes in the pelvic statics may lead to changed function or overstrain of advertising muscles.


Subject(s)
Athletic Injuries/physiopathology , Gait , Hip Injuries/physiopathology , Pelvis/physiopathology , Soccer/injuries , Soccer/physiology , Sprains and Strains/physiopathology , Humans , Pilot Projects
14.
Geobiology ; 6(3): 201-13, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18459966

ABSTRACT

The interactions between the geosphere and the biosphere are central questions in environmental and geological research. The relationship between bacteria and their environment is an important example of these interactions. By studying microbial communities in modern environments, it is possible to understand the underlying mechanisms that shape these environments and apply this knowledge to the rock record. Recently, new experimental and theoretical methods, ranging from nano- and biotechnology to mathematical and conceptual modelling, have come into play. Thus, new opportunities for interdisciplinary research in the field of geobiology have emerged. In this paper, we review aspects of state-of-the-art imaging and modelling techniques and propose a research concept linking the experimental and the theoretical approaches.


Subject(s)
Bacteria/metabolism , Cell Wall/metabolism , Ecosystem , Minerals/chemistry , Models, Biological , Water Microbiology , Bacteria/ultrastructure , Microscopy, Atomic Force , Microscopy, Electron, Transmission
15.
Int J Clin Pract ; 61(11): 1798-804, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17935544

ABSTRACT

BACKGROUND: Small dense low-density lipoprotein (LDL) particles are known to be especially atherogenic. Several mechanisms are involved in this atherogenicity. AIMS: We wanted to look for the presence of small dense LDL particles depending on gender, metabolic syndrome (MS) and different degrees of glucose intolerance. Moreover, we looked for anthropometric factors and factors of lipid and carbohydrate metabolism that are associated with changes in the LDL size. RESULTS: We studied 752 persons (330 males, 422 females; age 40 +/- 17 years). LDL particle size was estimated with polyacrylamide gel electrophoresis. Males had smaller LDL particles than females. Probands with the MS had smaller LDL particles than those without this syndrome. With rising plasma triglyceride (TG) levels more small dense LDL particles were seen. The highest proportion of these small dense LDL particles was observed in the subgroup of type 2 diabetic patients. In the whole material, the mean LDL diameter was correlated negatively with plasma TG and very low-density lipoprotein components (TG, cholesterol and proteins) and positively with high-density lipoprotein cholesterol. In a linear stepwise regression analysis different significant factors influencing the LDL size were found in the whole population, in normoglycaemic probands, in persons with impaired glucose tolerance, in type 2 diabetic patients and in type 2 diabetic patients injecting insulin. CONCLUSIONS: Our data point to different mechanisms of the formation of small dense LDL particles in dependence on the degree of glucose intolerance. Moreover, the target values for plasma TG should be set lower.


Subject(s)
Cholesterol, LDL/chemistry , Glucose Intolerance/metabolism , Metabolic Diseases/metabolism , Adult , Anthropometry , Cholesterol, LDL/biosynthesis , Cholesterol, VLDL/biosynthesis , Cholesterol, VLDL/chemistry , Female , Humans , Male , Middle Aged , Regression Analysis , Sex Factors , Syndrome
16.
Cancer Inform ; 3: 399-420, 2007 Dec 12.
Article in English | MEDLINE | ID: mdl-19455257

ABSTRACT

Aiming to find key genes and events, we analyze a large data set on diffuse large B-cell lymphoma (DLBCL) gene-expression (248 patients, 12196 spots). Applying the loess normalization method on these raw data yields improved survival predictions, in particular for the clinical important group of patients with medium survival time. Furthermore, we identify a simplified prognosis predictor, which stratifies different risk groups similarly well as complex signatures. We identify specific, activated B cell-like (ABC) and germinal center B cell-like (GCB) distinguishing genes. These include early (e.g. CDKN3) and late (e.g. CDKN2C) cell cycle genes. Independently from previous classification by marker genes we confirm a clear binary class distinction between the ABC and GCB subgroups. An earlier suggested third entity is not supported. A key regulatory network, distinguishing marked over-expression in ABC from that in GCB, is built by: ASB13, BCL2, BCL6, BCL7A, CCND2, COL3A1, CTGF, FN1, FOXP1, IGHM, IRF4, LMO2, LRMP, MAPK10, MME, MYBL1, NEIL1 and SH3BP5. It predicts and supports the aggressive behaviour of the ABC subgroup. These results help to understand target interactions, improve subgroup diagnosis, risk prognosis as well as therapy in the ABC and GCB DLBCL subgroups.

17.
Drug Deliv ; 13(1): 25-30, 2006.
Article in English | MEDLINE | ID: mdl-16401590

ABSTRACT

Biodegradable implantable matrices containing bovine serum albumin were prepared from oligoesters by melting, and subsequently tested on in vitro albumin release. The linear poly (DL-lactic acid) and the branched terpolymer of DL-lactic acid, glycolic acid, and mannitol were synthesized. Products were of similar molecular weight and possessed different thermal and swelling characteristics. Oligoesters were loaded with 4% albumin and plasticized by 30% triacetin. Other additives added into the matrices as albumin stabilizers were divalent stearates and magnesium oxide. The influences of oligomer molecules constitution, divalent ion stearates or magnesium oxide addition, and triacetin concentration on the albumin release were quantified. SDS-PAGE revealed protein hydrolysis during the dissolution tests.


Subject(s)
Albumins/chemistry , Magnesium Oxide/chemistry , Calcium/chemistry , Drug Compounding , Electrophoresis, Polyacrylamide Gel , Esters/chemistry , Hydrogen-Ion Concentration , Plastics , Serum Albumin, Bovine/chemistry , Stearic Acids
18.
Ceska Slov Farm ; 55(6): 262-6, 2006 Nov.
Article in Czech | MEDLINE | ID: mdl-17288061

ABSTRACT

Adhesive force of branched oligoesters under the in vitro conditions was studied by measuring the maximal force necessary to separate the tested sample from the base (F(max)) under different testing conditions. Branched oligoesters were synthesized from lactic and glycolic acids in the molar ratio 1:1, and from mannitol or dipentaery thritol as the branching components in concentrations of 3%, 5% or 8%. To decrease viscosity and thus to facilitate the workability and administration, triethyl citrate (TEC) in a concentration of 30% was employed. Polymeric systems for adhesive force measurements were prepared by melting oligoesters in a micro oven and by homogenization with TEC. Adhesive force was measured on a material testing device T1-FR050TH.A1K Zwick/Roell at the set rate of separation 10 mm/min or 100 mm/min, contact force 10 N or 20 N, and a period of contact of the sample with the base of 5 s or 10 s. The adhesive force of branched oligoesters was found to be significantly higher than the adhesive force of gelatine gels, methylcellulose, carmelose sodium salt or sodium carbomer salt. Dipentaerythritol-branched oligoesters exerted higher adhesive force than mannitol-branched oligoesters. The value of adhesive force was increased with growing concentration of the branching component in the oligoester. Of the experimental parameters tested, a statistically significant influence of the separation rate of the sample from the base on the magnitude of F(max) was observed. The influence of different periods of contacts was manifested only in some samples, and the influence of different contact forces on F(max) value was not demonstrated in any sample.


Subject(s)
Materials Testing , Polymers , Adhesiveness , Biocompatible Materials
19.
Ceska Slov Farm ; 53(4): 177-82, 2004 Jul.
Article in Czech | MEDLINE | ID: mdl-15369228

ABSTRACT

Thin films were prepared by the method of evaporation of aqueous solutions of chitosan or its mixtures with poloxamer 407, gelatin, or polyvinyl alcohol. Films of varying thickness were cross-linked with phosphate ions. They contained micronized folic acid in a concentration of 9.1% or 3.2%. Prolonged several hours' liberation of folic acid into isotonic phosphate buffer at pH 5.5, 6.0, and 6.5 was examined. In the initial stage, the mechanism of liberation was governed by diffusion of the dissolved fraction, at higher pH values a higher rate of dissolution of the substance played its role. In some composites, sorption of folic acid to chitosan in an extent dependent on the composition of composites and current acidity of the medium was demonstrated.


Subject(s)
Chitosan/chemistry , Folic Acid/chemistry , Biocompatible Materials , Chemical Phenomena , Chemistry, Pharmaceutical , Chemistry, Physical
20.
Rofo ; 176(9): 1245-50, 2004 Sep.
Article in German | MEDLINE | ID: mdl-15346258

ABSTRACT

PURPOSE: Quantification of left and right ventricular function using MRI in young cancer patients treated with cardiotoxic anthracyclines. MATERIALS AND METHODS: Twenty-eight patients (mean age 16.4 years) underwent cardiac MRI at 1.5 T. The study protocol consisted of morphologic T2-weighted images with fat suppression and cine steady-state free precession sequences (SSFP) for functional analysis. Seven patients were examined at the end of chemotherapy, two of them also repeatedly during therapy, and 21 patients following an average period of three years after finishing chemotherapy (range one month--20 years) RESULTS: The end-systolic volume index increased and the ejection fraction of the left and right ventricle decreased during anthracycline therapy. Two of seven patients showed a myocardial edema at the end of the therapy. In 15 of all 28 patients, the left ventricular ejection fraction was reduced to less than 55 % (minimum 44 %). No clinical signs of cardiac insufficiency or cardiomyopathy were observed. CONCLUSION: MRI is able to detect acute as well as chronic subclinical cardiotoxic effects of anthracyclines. Impairment of the right ventricular function should be considered in the diagnosis of anthracycline-induced cardiomyopathy.


Subject(s)
Anthracyclines/adverse effects , Cardiomyopathies/chemically induced , Cardiomyopathies/diagnosis , Magnetic Resonance Imaging/methods , Neoplasms/drug therapy , Stroke Volume , Ventricular Function , Adolescent , Adult , Age Factors , Anthracyclines/therapeutic use , Child , Echocardiography , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging, Cine , Male , Time Factors , Ventricular Function, Left , Ventricular Function, Right
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