Liesegang's rings resembling helminthiasis

So called Liesegang's rings are lamellar corpuscles which develop after periodical precipitation of oversaturated solutions in gel medium. They can occur in cysts, closed cavities, inflammatory exudates and necroses. They resemble parasitic eggs, larvae or adult forms. A case of 28-year-old woman is presented with many Liesegang's rings in a stuff from dilated renal calyx. Their preliminary evaluation considered helminths, especially Dioctophyma renale.     

Über Melanin und Melanosomen im ZNS im Vergleich zu extracerebralen Erscheinungsformen und synthetischem Melanin aus Dopamin und Serotonin

Summary Melanosomes and isolated melanosomal fragments (melanin particles) originating from gangliocytes (substantia nigra), astroglia (melanosis cerebelli), and melanocytes (melanotic meningeoma; metastases of melanoblastoma; melanosis thalami of the goat) were compared with synthetic melanins prepared from dopamine and serotonin, respectively. Samples were examined by electron microscopy, X-ray diffraction analysis according to Debye-Scherrer and by infrared spectrophotometry, and the results were evaluated with regard to characteristic features as they may relate to specific cell types or chemical structures.On electron microscopy all three types of melanosomes could be differentiated unequivocally as could the two synthetic melanins. Thus, there were similarities between synthetic melanin from dopamine and the gliogenic melanins of the cerebellum; the synthetic melanin from serotonin resembled melanin of melanocytes.X-ray diffraction analysis yielded 2-4 Debye diffraction rings with all human and synthetic samples, suggesting short range orders between 3.8 to 5 Å the sample obtained from a goat with thalamic melanosis showed a specific reflex pattern. While diffraction patterns of some melanins were partially identical, in particular that of melanin from dopamine and melanin of substantia nigra and dentate nucleus, respectively, they were different for the various melanocytic melanins. Further investigations are required to determine whether these differences are due to disparities in basic chemical structures or conformations or else, to particular compositional features of the various types of melanocytes as they arise from benign or malignant tumors or a specific species.Infrared spectrophotometry at higher wave numbers revealed the well known patterns of melanins, which are not, however, very suitable, for their further differentiation. At lower wave numbers (fingerprinting) melanin of substantia nigra and the glial melanin in melanosis cerebelli yielded additional absorption bands of identical configuration. In contrast to melanin from dopamine, melanin from serotonin exhibited a closely similar absorption pattern in this spectral range, suggesting that the neuroectodermal melanins may contain a component possibly arising from serotonin.

Herrn Prof. Dr. Wilhelm Doerr zum 25. 8. 1979     

Die analyse von aluminium im serum und urin zur überwachung emonierter personen

Zusammenfassung Die Einführnung der flammenlosen Atomabsorptionsspektrometrie in die chemische Analytik ermöglicht eine einfache quantitative Bestimmung des Aluminiums im biologischen Material. Die verwendeten Analysen-methoden und deren Zuverlässigkeitskriterien wurden beschrieben. Entsprechend der heute üblichen Verfahren zur Überwachung schwermetallexponierter Personen wurden von uns bei verschiedenen Kollektiven Aluminiumbestimmungen im Blut und Urin durchgeführt. Untersucht wurde ein Kollektiv von 110 Arbeitern eines Korund-herstellenden und -verarbeitenden Werkes. 82 dieser Arbeiter waren durch staubförmigen Korund exponiert, während 28 Personen an den Öfen zusätzlich noch Metalldämpfen ausgesetzt waxen. Die Expositionsdauer betrug im Mittel 6,9 Jahre. Als Vergleichskollektiv dienten 40 männliche nicht aluminiumexponierte Probanden. Zusädtzlich wurden 33 Dialyse-Patienten, die mit Aluminiumhydroxid (Aludrox) therapiert wurden, in die Studie einbezogen.Für die Aluminiumausscheidung im Urin errechnete sich bei den Normalpersonen eine obere Normgrenze von 30 g/l. Die Ausscheidungswerte der aluminiumexponierten Personen lagen mit einem Median von 39 g Al/l signifikant höher als das Normalkollektiv. Erwartungsgemä zeigten die dampfförmig belasteten Personen einen statistisch signifikant höheren Al-Spiegel im Urin als die staubförmig belastete Gruppe.Die Serumanalysen ergaben keine Hinweise für einen signifikanten Unterschied gegenüber Normalpersonen. Aus den Untersuchungen der Seren von nicht aluminiumexponierten Probanden errechnete sich ein oberer Grenzwert von 35 g/l. Der Serum-Aluminium-Spiegel der exponierten Personen war von der Art und Dauer der Exposition nicht beeinflut. Dagegen lagen die Aluminium-Spiegel im Serum der Dialyse-Patienten im Bereich von 6 – 254 g/l. Bei dieser Patientengruppe mit erhöhten Serum-Aluminiumwerten wurden keine klinischen Zeichen einer manifesten Toxicität gefunden. Damit kommt den Aluminiumkonzentrationen im biologischen Material der aluminiumexponierten Arbeiter keine gesundheitsgefahrdende Relevanz zu.Bei der inhalativen Aufnahme von Aluminium scheint die Menge des resorbierten und in die Blutbahn übergehenden Aluminiums gering zu sein. Hinweise für eine Akkumulation des Metalls im Organismus wurde bei Versuchen mit D-Penicillamin nicht gefunden.Aluminiumbestimmungen im Serum oder Harn sind für die Überwachung von Korund-herstellenden und -verarbeitenden Personen nach diesen Ergebnissen nicht notwendig. Bei Substanzen, wie dem Aluminium, mit geringer Resorptions-quote und groer Toleranzbreite für den menschlichen Organismus sowie ohne manifeste signifikante Gesundheitsschäden erscheint ein Biological Monitoring nicht indiziert.D 29     

LHRH-Agonist-Behandlung von kleinwüchsigen Jugendlichen

Ohne Zusammenfassung     

La protonterapia: indicaciones y perspectivas

Protons have considerable targeting advantages in the conduct of precise conformational radiotherapy, enabling dose escalation and a better protection of critical organs. Protons differs from photons and electrons used in classical radiotherapy due to their specific physical characteristics, Bragg peak and narrow lateral penumbra. Currently, treatment of ocular melanoma, chordoma and chondrosarcoma of the base of skull and paediatric tumours are widely accepted. Others clinical indications are still being evaluated (meningioma, etc.). Generalised isocentric application and proton intensity modulation can increase the clinical indications for its use. It is a technique which, despite its current expansion, appears “restricted” because of the scarcity of equipments due to its high cost.     

Donor treatment with mycophenolate mofetil: protection against ischemia-reperfusion injury in the rat

BACKGROUND: Mycophenolic acid, the active metabolite of mycophenolate mofetil, inhibits the glycosylation of cell membrane glycoproteins. We hypothesized that impaired glycosylation of cell adhesion molecules on endothelial cells in vivo results in decreased susceptibility to inflammation or immunogenicity after allogeneic transplantation. METHODS: The expression of mannose residues on cultured rat endothelial cells was examined after stimulation with interleukin 1 in the presence or absence of mycophenolic acid using labeled Galanthus nivalis agglutinin. The in vitro adhesion of blood leukocytes to heart tissue was examined using peripheral blood leukocytes of recipient origin and sections of donor heart tissue exposed to ischemia-reperfusion injury after pretreatment with vehicle or mycophenolic mofetil. (LEWxBN)F1 donor rats were treated with 20 or 60 mg/kg/day of mycophenolate mofetil for 1 or 2 weeks followed by transplantation of the heart into Lewis recipients after storage in heparin-containing normal saline for either 10 min at 4 degrees C or 120 min at room temperature. RESULTS: Endothelial cells stimulated in vitro with interleukin 1 showed an increase in a population of strongly mannose-positive cells, which was prevented by the addition of mycophenolic acid during the culture. The in vitro adhesion of peripheral blood leukocytes to cardiac tissue sections exposed to prolonged storage and reperfusion was significantly less if the donor had been treated with mycophenolate mofetil. Treatment of cardiac graft donors with mycophenolate mofetil protected the graft against early graft failure after prolonged storage at room temperature, because the mean graft survival was 9.4+/-0.6 days for grafts that came from donors treated with mycophenolate mofetil versus 1.2+/-0.9 days (P<0.05) for grafts that came from vehicle-treated donors. Donor pretreatment with mycophenolate mofetil did not affect the survival time of heart grafts transplanted after 15 min of standard cold storage or the survival of grafts transplanted into presensitized recipients. CONCLUSION: Donor treatment with mycophenolate mofetil protects cardiac grafts against primary nonfunction after prolonged tepid storage, which may be related to the inhibition of glycosylation of cell adhesion molecules involved in ischemia-reperfusion injury.     

Electromotive administration of intravesical bethanechol and the clinical impact on acontractile detrusor management: introduction of a new test

PURPOSE: It is often difficult to determine the functional status of the detrusor muscle in patients with detrusor areflexia. We performed a clinical study to establish a test defining residual detrusor capacity in such patients. MATERIALS AND METHODS: In phase 1, 5 controls with detrusor areflexia were tested with an intravesical instillation of 20 mg. bethanechol in 150 cc of sodium chloride 0.3% with and without 20 mA. of pulsed current applied via an electrode catheter through the saline. Cystometry simultaneously recorded intravesical pressure changes. In phase 2, 45 patients with detrusor areflexia were tested with electromotive administration of intravesical bethanechol. In phase 3, 25 mg. bethanechol given orally once daily were prescribed for 15 patients and voiding control was assessed after 6 weeks of therapy. RESULTS: Neither bethanechol without current nor current through saline only led to increased intravesical pressure. However, we noted a mean pressure increase of 34 cm. water during the electromotive administration of bethanechol in 24 of 26 patients with areflexia and neurological disease compared to only 3 cm. water in 3 of 11 with a history of chronic bladder dilatation. Oral bethanechol restored spontaneous voiding in 9 of 11 patients who had had a positive response to the electromotive administration of bethanechol, whereas all 4 without a pressure increase during the electromotive administration of bethanechol did not void spontaneously. CONCLUSIONS: Electromotive administration of intravesical bethanechol identifies patients with an atonic bladder and adequate residual detrusor muscle function who are candidates for restorative measures, such as oral bethanechol and intravesical electrostimulation. Those who do not respond to the electromotive administration of bethanechol do not benefit from oral bethanechol and are candidates for catheterization.     

Value of non-clinical cardiac repolarization assays in supporting the discovery and development of safer medicines

Non-clinical QT-related assays aligned to the pharmaceutical drug discovery and development phases are used in several ways. During the early discovery phases, assays are used for hazard identification and wherever possible for hazard elimination. The data generated enable us to: (i) establish structure–activity relationships and thereby; (ii) influence the medicinal chemistry design and provide tools for effective decision making; and provide structure–activity data for in silico predictive databases; (iii) solve problems earlier; (iv) provide reassurance for compound or project to progress; and (v) refine strategies as scientific and technical knowledge grows. For compounds progressing into pre-clinical development, the ‘core battery’ QT-related data enable an integrated risk assessment to: (i) fulfil regulatory requirements; (ii) assess the safety and risk–benefit for compound progression to man; (iii) contribute to defining the starting dose during the phase I clinical trials; (iv) influence the design of the phase I clinical trials; (v) identify clinically relevant safety biomarkers; and (vi) contribute to the patient risk management plan. Once a compound progresses into clinical development, QT-related data can be applied in the context of risk management and risk mitigation. The data from ‘follow-up’ studies can be used to: (i) support regulatory approval; (ii) investigate discrepancies that may have emerged within and/or between non-clinical and clinical data; (iii) understand the mechanism of an undesirable pharmacodynamic effect; (iv) provide reassurance for progression into multiple dosing in humans and/or large-scale clinical trials; and (v) assess drug–drug interactions. Based on emerging data, the integrated risk assessment is then reviewed in this article, and the benefit–risk for compound progression was re-assessed. Project examples are provided to illustrate the impact of non-clinical data to support compound progression throughout the drug discovery and development phases, and regulatory approval.This article is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010     

Germanium Nanoparticles Prepared by Laser Ablation in Low Pressure Helium and Nitrogen Atmosphere for Biophotonic Applications

Due to particular physico-chemical characteristics and prominent optical properties, nanostructured germanium (Ge) appears as a promising material for biomedical applications, but its use in biological systems has been limited so far due to the difficulty of preparation of Ge nanostructures in a pure, uncontaminated state. Here, we explored the fabrication of Ge nanoparticles (NPs) using methods of pulsed laser ablation in ambient gas (He or He-N₂ mixtures) maintained at low residual pressures (1–5 Torr). We show that the ablated material can be deposited on a substrate (silicon wafer in our case) to form a nanostructured thin film, which can then be ground in ethanol by ultrasound to form a stable suspension of Ge NPs. It was found that these formed NPs have a wide size dispersion, with sizes between a few nm and hundreds of nm, while a subsequent centrifugation step renders possible the selection of one or another NP size fraction. Structural characterization of NPs showed that they are composed of aggregations of Ge crystals, covered by an oxide shell. Solutions of the prepared NPs exhibited largely dominating photoluminescence (PL) around 450 nm, attributed to defects in the germanium oxide shell, while a separated fraction of relatively small (5–10 nm) NPs exhibited a red-shifted PL band around 725 nm under 633 nm excitation, which could be attributed to quantum confinement effects. It was also found that the formed NPs exhibit high absorption in the visible and near-IR spectral ranges and can be strongly heated under photoexcitation in the region of relative tissue transparency, which opens access to phototherapy functionality. Combining imaging and therapy functionalities in the biological transparency window, laser-synthesized Ge NPs present a novel promising object for cancer theranostics.     

Triterpene glycosides from Antarctic sea cucumbers. 1. Structure of liouvillosides A1, A2, A3, B1, and B2 from the sea cucumber Staurocucumis liouvillei: new procedure for separation of highly polar glycoside fractions and taxonomic revision

Five new triterpene glycosides, liouvillosides A1 (1), A2 (2), A3 (3), B1 (4), and B2 (5), have been isolated from the Antarctic sea cucumber Staurocucumis liouviellei along with the known liouvilloside A(6), isolated earlier from the same species, and hemoiedemosides A (7) and B (8), isolated earlier from the Patagonian sea cucumber Hemioedema spectabilis. The isolation was carried out using a new chromatographic procedure including application of ion-pair reversed-phase chromatography followed by chiral chromatography on a cyclodextrin ChiraDex column. The structures of the new glycosides were elucidated using extensive NMR spectroscopy (1H and 13C NMR spectrometry, DEPT, 1H-(1)H COSY, HMBC, HMQC, and NOESY), ESI-FTMS, and CID MS/MS, and chemical transformations. Glycosides 1-3 are disulfated tetraosides and glycosides 4 and 5 are trisulfated tetraosides. Glycosides 2 and 3 contain 3-O-methylquinovose, found for the first time as a natural monosaccharide in sea cucumber glycosides. On the basis of analyses of glycoside structures a taxonomic revision is proposed.