Vollzähligkeitsschätzungen von Krebsregisterdaten in Deutschland

In 1995, a federal cancer registry law became effective in Germany obliging all federal states to set up epidemiological cancer registries. As a result,numerous cancer registries have been established. However, it is essential to know the degree to which all relevant cases are recorded within a registry—particularly for those registries established recently—as only a high degree of completeness can prevent variations in the efficacy of registry procedures from distorting comparative studies. In this study, the completeness of the cancer registries was evaluated indirectly. Incidences for geographical areas covered by a cancer registry were estimated using incidence/mortality ratios of another registry known to have complete data sets. Log-linear models, successfully applied in a separate study, were fitted to incidence/mortality ratios using both the age and sex-specific data of the reference registry. These estimates were then compared with the actual data collected by the newly established registry, allowing the level of completeness to be assessed. The German Epidemiological Cancer Registry Study Group has agreed to this method and the "Dachdokumentation Krebs"—as a member of this group—performs the analyses. The first results of the study are presented in this contribution.     

Weitere Entwicklung der Krebssterblichkeit in Deutschland bis zum Jahr 2010

Ohne Zusammenfassung     

über die antikörperinaktivierende Wirkung der Antirheumatica

Zusammenfassung Die Antirheumatica Prednisolon, Phenylbutazon, Resochin, Natriumgentisinat und Natriumsalicylat hemmen die durch hämolytischen Hammelblutamboceptor und Komplement bewirkte Hammelbluthämolyse.Diese Wirkung der Antirheumatica kommt durch eine Inaktivierung des Amboceptors (Antikörpers) zustande. Das Komplement und die Hammelblutkörperchen werden bei diesen Versuchen von den Antirheumatica nicht beeinflußt.Es besteht eine strenge quantitative Beziehung zwischen Amboceptorkonzentration und Antirheumaticumkonzentration. Je höher die Konzentration des Amboceptors ist, um so stärkere Antirheumaticakonzentrationen sind zu seiner Inaktivierung nötig.Bezogen auf die wirksamen molaren Endkonzentrationen sind Prednisolon 8,5, Phenylbutazon 6,5, Resochin 5,0 und Gentisinsäure 1,5mal stärker wirksam als Salicylsäure.Wird der Amboceptor mit bestimmten Konzentrationen von Phenylbutazon, Natriumgentisinat oder Natriumsalicylat vorbehandelt, so kann mit diesem Amboceptor der Forssman-Schock (invers-anaphylaktischer Schock) nicht mehr beim Meerschweinchen ausgelöst werden. Phenylbutazon und Natriumgentisinat sind dabei etwa gleichstark wirksam, während Natriumsalicylat wesentlich schwächer wirkt als die beiden anderen Substanzen.     

Hirndurchblutung und cerebraler Stoffwechsel bei Kranken mit chronischer Niereninsuffizienz

Zusammenfassung 1. Bei 24 Kranken mit chronischer Niereninsuffizienz und Urämie wurden die Hirndurchblutungsgröße quantitativ mit der Stickoxydulmethode und der cerebrale Stoffwechsel mit enzymatischen Methoden untersucht.2. Bei einem Harnstoff-N von 142 mg-% und einem arteriellen pH von 7,31 lag die Hirndurchblutungsgröße mit 63,0 ml/100 g · min gering über der Norm. Der cerebrale O₂-Verbrauch (2,77 ml/100 g · min) und der cerebrale Glucoseverbrauch (3,75 mg/100 g · min) waren stark vermindert. Der Glucose-Oxydationsquotient war mit 1,13 gering reduziert. Die cerebrale Lactat- und Pyruvatabgabe unterschieden sich nicht sicher von der Norm. Der respiratorische Quotient lag mit 0,89 tiefer als normal.3. Die Aufschlüsselung des Materials in acidotische (pH<7,35) und nichtacidotische (pH>7,35) Urämien ergab unterschiedliche Resultate:a) Bei 15 acidotischen Urämien war die Hirndurchblutungsgröße mit 69,0 ml/100 g · min erhöht. Die Korrelationsberechnung zeigt, daß eine gesicherte negative Beziehung zwischen pH und Hirndurchblutungsgröße besteht: Je stärker die Acidose, desto höher die Durchblutung.Die cerebrale O₂-Aufnahme war mit 2,62 ml/100 g · min und die Glucoseaufnahme mit 3,33 mg/100 g · min signifikant vermindert. Der Glucose-Oxydationsquotient war mit 0,98 sehr stark reduziert.b) Bei 9 nichtacidotischen Urämien lag die Hirndurchblutung mit 52,9 ml/100 g · min im Normbereich, während der O₂-Verbrauch mit 2,96 ml/100 g · min und der Glucoseverbrauch mit 4,52 mg/100 g · min reduziert waren. Der Glucoseverbrauch war deutlich weniger vermindert als bei den acidotischen Urämien. Daher unterscheidet sich in dieser Gruppe der Glucose-Oxydationsquotient nicht signifikant von der Norm.4. Es besteht eine statistisch gesicherte positive Korrelation von pH und O₂- bzw. Glucoseverbrauch, d.h. je stärker die Acidose, desto niedriger sind O₂- und Glucoseaufnahme. Zur Höhe des Harnstoff-N besteht keine Korrelation.5. Unter der Therapie mit Abfall des Harnstoff-N und Anstieg des pH besserten sich cerebrale O₂- und Glucoseaufnahme und normalisierte sich der Glucose-Oxydationsquotient.6. Es besteht eine Beziehung von cerebraler Funktion (Sensorium klar, getrübt, Praecoma, Coma) zu den cerebralen O₂- und Glucoseutilisationswerten, nicht hingegen zur Durchblutungsgröße.7. Die urämische Encephalopathie ist Folge einer acidotisch-toxischen Stoffwechseldepression und geht nicht mit einer cerebralen Zirkulationsstörung einher.Meinen akademischen Lehrern Prof. Dr. Dr. G. Bodechtel und Prof. Dr. A. Bernsmeier zu ihren Geburtstagen im März 1972.     

Histone H1-mediated transfection: role of calcium in the cellular uptake and intracellular fate of H1-DNA complexes

Previously, we have shown that the transgene expression in the endothelial cell line ECV 304 strongly depends on the presence of low concentrations of Ca2+. However, it remained unclear, which transfection steps are controlled by Ca2+ ions. In the present study, we constructed transfection complexes of digoxigenin-labelled DNA and FITC-labelled histone H1. We monitored the pathway of these complexes with the use of anti-digoxigenin and anti-cathepsin B antibodies and immunofluorescence microscopy. Double labelling of DNA and cathepsin B permitted the localization of transfection complexes into endosomes/lysosomes which suggests an uptake of transfection complexes via endocytosis. It was also found that the uptake of transfection complexes by the cells was independent of the presence or absence of Ca2+ ions in the transfection medium. On the other hand, the presence of Ca2+ in the transfection medium dramatically changed the composition of the transfection complexes inside the endosome/lysosome compartment, which resulted in a strong reduction of H1 binding to DNA. Presence of Ca2+ in the postincubation medium for 24 h resulted in release of the transfection complexes with reduced H1 content from the endosomes/lysosomes into the cytosol. In the absence of Ca2+ the transfection complexes practically disappeared. These results allow us to come to the following conclusions: Ca2+ ions control the reorganization of the transfection complexes in endosomes/lysosomes and their release into the cytosol, which is an important prerequisite for transgene expression, whereas uptake of transfection complexes by the cells is not dependent on Ca2+.     

Characterization of Aptamer BC 007 Substance and Product Using Circular Dichroism and Nuclear Magnetic Resonance Spectroscopy

Possible unwanted folding of biopharmaceuticals during manufacturing and storage has resulted in analysis schemes compared to small molecules that include bioanalytical characterization besides chemical characterization. Whether bioanalytical characterization is required for nucleotide-based drugs, may be decided on a case-by-case basis. Nucleotide-based pharmaceuticals, if chemically synthesized, occupy an intermediate position between small-molecule drugs and biologics. Here, we tested whether a physicochemical characterization of a nucleotide-based drug substance, BC 007, was adequate, using circular dichroism (CD) spectroscopy. Nuclear magnetic resonance confirmed CD data in one experimental setup. BC 007 forms a quadruplex structure under specific external conditions, which was characterized for its stability and structural appearance also after denaturation using CD and nuclear magnetic resonance. The amount of the free energy (ΔG⁰) involved in quadruplex formation of BC 007 was estimated at +8.7 kJ/mol when dissolved in water and +1.4 kJ/mol in 154 mM NaCl, indicating structural instability under these conditions. However, dissolution of the substance in 5 mM of KCl reduced the ΔG⁰ to ?5.6 kJ/mol due to the stabilizing effect of cations. These results show that positive ΔG⁰ of quadruplex structure formation in water and aqueous NaCl prevents BC 007 from preforming stable 3-dimensional structures, which could potentially affect drug function.     

Aptamer BC 007’s Affinity to Specific and Less-Specific Anti-SARS-CoV-2 Neutralizing Antibodies

COVID-19 is a pandemic respiratory disease that is caused by the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Anti-SARS-CoV-2 antibodies are essential weapons that a patient with COVID-19 has to combat the disease. When now repurposing a drug, namely an aptamer that interacts with SARS-CoV-2 proteins for COVID-19 treatment (BC 007), which is, however, a neutralizer of pathogenic autoantibodies in its original indication, the possibility of also binding and neutralizing anti-SARS-CoV-2 antibodies must be considered. Here, the highly specific virus-neutralizing antibodies have to be distinguished from the ones that also show cross-reactivity to tissues. The last-mentioned could be the origin of the widely reported SARS-CoV-2-induced autoimmunity, which should also become a target of therapy. We, therefore, used enzyme-linked immunosorbent assay (ELISA) technology to assess the binding of well-characterized publicly accessible anti-SARS-CoV-2 antibodies (CV07-209 and CV07-270) with BC 007. Nuclear magnetic resonance spectroscopy, isothermal calorimetric titration, and circular dichroism spectroscopy were additionally used to test the binding of BC 007 to DNA-binding sequence segments of these antibodies. BC 007 did not bind to the highly specific neutralizing anti-SARS-CoV-2 antibody but did bind to the less specific one. This, however, was a lot less compared to an autoantibody of its original indication (14.2%, range 11.0–21.5%). It was also interesting to see that the less-specific anti-SARS-CoV-2 antibody also showed a high background signal in the ELISA (binding on NeutrAvidin-coated or activated but noncoated plastic plate). These initial experiments suggest that the risk of binding and neutralizing highly specific anti-SARS CoV-2 antibodies by BC 007 should be low.     

Impact of a functionalized olive oil extract on the uterus and the bone in a model of postmenopausal osteoporosis

Purpose

The Mediterranean diet rich in fruits, vegetables and olive oil has been related to a lower osteoporosis incidence and accordingly to a reduced fracture risk. These observations might be mediated by the active constituents of extra virgin olive oil, and especially polyphenols. In the context of exploring the features of olive oil active constituents on postmenopausal osteoporosis, an extra virgin olive oil total polyphenolic fraction (TPF) was isolated and its effect on the bone loss attenuation was investigated.

Methods

Female Lewis rats were ovariectomized and fed a diet enriched with a total phenolic extract of extra virgin olive oil in a concentration of 800 mg/kg diet.

Results

Oleocanthal, one compound of the polyphenolic fraction, showed a higher relative estrogen receptor binding affinity to the ERα compared to the ERβ. While the TPF only slightly induced the uterine wet weight (490.7 ± 53.7 vs. 432.7 ± 23, p = 0.058), TPF regulated estrogen response genes in the uterus (progesterone receptor, antigen identified by monoclonal antibody Ki67, complement C3). Comparing the quantified bone parameters, the oral TPF substitution did not attenuate the ovariectomy-induced bone loss.

Conclusions

The administration of extra virgin olive oil polyphenols regulated uterine estrogen response marker genes in an E2-agonistic manner. The bone loss induced by estrogen ablation was not mitigated by treatment with the polyphenolic extract.