Universität Stuttgart
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Item Open Access Pulsed high-power-sonication of concrements, cancer cells and rodent-tumors in vivo(1989) Riedlinger, Rainer E.; Brümmer, Franz; Hülser, Dieter F.Extracorporeal lithotripsy has been successfully established, based on different principles of generating and focusing the shock waves. Lithotripters have also been used to investigate the influence of shocks to cancer cells and solid tumors. With two different trans-mitters (spark-gap type XL-1 and piezo-resonance type MW 2) we applied shock waves and short high power US-pulses to suspended and immobilized tumor cells and multicell spheroids. With MW 2 significant local damage on cell spheroids in gelatin was achieved, caused by locally controlled cavitation. The results are compared to each other.Item Open Access Histopathology of shock wave treated tumor cell suspensions and multicell tumor spheroids(1989) Bräuner, Thomas; Brümmer, Franz; Hülser, Dieter F.L1210 mouse leukemia cell suspensions exposed to 500 shock waves (SW) in an experimental lithotripter (XLI, Dornier) revealed severe cellular damage. Apart from cell fragments and cellular debris, cells exhibited alterations of shape, vacuolisation of the cytoplasm, perinuclear cisternae, swelling of mitochondria or rupture of the mitochondrial fine structure, and permeabilization of the cell membrane. Treatment of multicell tumor spheroids of both HeLa and EMT6/Ro cells in suspension with 500 SW resulted either in loss of peripheral cells and serious cellular damage in the outer regions or in a fragmentation of the spheroids. Many of the geometrically intact cells exhibited the same histopathological alterations as the suspended L1210 cells. Immobilization of the spheroids in agar or gelatine, however, prevented spheroids from being agitated and accelerated during SW-exposure. After treatment with 500 SW, spheroids immobilized in gelatine were not different from control cultures, as investigated with light- and electronmicroscopy. From our results we conclude that spheroids in suspension are subject to cavitation and liquid jet formation, causing not only acceleration and shearing forces but also collisions which account for the observed cell damage.Item Open Access Biological effects and physical characterization of shock waves by an XL-1 experimental lithotripter(1989) Brümmer, Franz; Staudenraus, Joachim; Nesper, Martina; Suhr, Dierk; Eisenmenger, Wolfgang; Hülser, Dieter F.Extracorporeal shock wave lithotripsy (ESWL) has become the clinical standard method for non-invasive disintegration not only of concrements in kidney and urinary tract but also of gallstones. Despite the widespread clinical use of ESWL, the mechanism of stone destruction is not yet really understood, but several possibilities (cavitation, shock wave reflection) are discussed. The final cause of various side effects is still under discussion. Nevertheless, during the last few years much effort was put into possible extensions of ESWL applications On the other hand , physical characterizations of shock waves are rarely reported and combined measurements of biological effects in vitro and physical characterization of the applied shock waves are not available. We, therefore, examined the influence of water temperature and gas content on the shock wave efficency in biological systems and determined several physical characteristics (pressure amplitudes, rise time etc.) of the shock waves under the same experimental conditions.Item Open Access Reduced cavitation-induced cellular damage by the antioxidative effect of vitamin E(1994) Suhr, Dierk; Brümmer, Franz; Irmer, Ulrich; Schlachter, Manfred; Hülser, Dieter F.Fragmentation of human urinary and biliary stones by shock waves in extracorporeal lithotripsy is accompanied by tissue damage. Both the fragmentation as well as the side effects are often attributed to cavitation. The hazardous potential of cavitation is not only of a physical nature but also of a chemical nature, because of the generation of free radicals, e.g. ·OH, ·H and ·O2. After the application of shock waves, we have demonstrated cavitation-generated free radicals in cell-free solutions and also in the surviving and intact suspended MGH-U1 cells by hydroethidine measurements. Under electron microscopical inspection, the same cells exhibited perinuclear cisternae, damaged mitochondria and numerous intracellular vacuoles. The contribution of free radicals to cell damage was investigated by reducing the vitamin E level in rats by a tocopherol free diet and by incubating L1210 cells in a tocopherol enriched medium. After 250 shock waves, ex vivo erythrocytes revealed a 75% increase in total cell disruption over cells from non-depleted rats. The in vitro experiments with L1210 cells exhibited a moderate protection by the addition of this scavenger of free radicals.Item Open Access Biophysical investigations of the in vitro effects of shock waves and ultrasound(1993) Brümmer, Franz; Suhr, Dierk; Irmer, Ulrich; Bachleitner, Christoph; Hülser, Dieter F.To investigate the interactions of ultrasonic waves with biological tissues, we developed and standardized several in vitro models. Using these systems - artificial stones, human erythrocytes, L1210 mouse leukemia cells, multicellular spheroids, cavitation assay - we are able to elucidate the mechanisms of interaction as well as the cause of clinically observed side effects.Item Open Access Sensivity of normal and malignant cells to shock waves(1992) Brümmer, Franz; Suhr, Dierk; Hülser, Dieter F.We examined the cytotoxic effect of shock waves for primary (embryonic chick kidney and thigh muscle) and permanently growing normal and malignant cells (human, rat, and mouse) in suspension. To avoid the influence of different media, the cells were suspended in phosphate buffered, saline and shock wave treated. In all cases the acute cytotoxic effect (measured by flow cytometry) was a function of the applied shock waves. The investigated cells differed in their LD 50 values which, however, do not reveal a general difference in sensitivity to shock waves for normal and malignant cells.Item Open Access A million cells in search for contact : multicell spheroids not only for cancer research(1987) Hülser, Dieter F.; Brümmer, Franz; Bräuner, ThomasThree-dimensional, spherical aggregates of cells - so-called multicell spheroids - have many practical applications. In cancer research, for example, they contribute to a drastic reduction in the number of experiments with animals. The authors of the following article were awarded a special DM 10,000 prize under the Felix-Wankel-Tierschutz-Forschungspreis in November 1986 for their work on intercellular communication in multicell spheroids.Item Open Access Are biological effects of shock waves caused by free radicals?(1991) Suhr, Dierk; Brümmer, Franz; Hülser, Dieter F.Stone fragmentation in extracorporeal shock wave lithotripsy as well as accompanying tissue damage are attributed to cavitation. We attempted to demonstrate and localize the occurrence of cavitation in cell-free solutions and MGH-U1 cells using sensitive dyes for the detection of cavitation-generated free radicals.Item Open Access Biological effects of shock waves(1990) Brümmer, Franz; Bräuner, Thomas; Hülser, Dieter F.Extracorporeal shock wave lithotripsy has become established worldwide as the method of choice for the treatment of nephrolithiasis and ureterolithiasis over the last 10 years. Although initial studies showed no damaging effects of the shock waves on organs and tissues, numerous recent reports have presented evidence for severe acute effects and chronic complications after shock wave treatment. The pathophysiological effects on kidneys and the histopathological effects on organs or tissues in man and animal, and also the effects on cells in culture and tumors are sumarized. Suspended and immobilized cell cultures were used to characterize and quantify the efficacy of shock wave. Extended applications of shock waves and possible modifications to shock wave generators are discussed.Item Open Access Schwamm drüber! - Vom Hygieneartikel zum Arzneilieferant aus dem Meer(2002) Brümmer, Franz; Nickel, MichaelJeder kennt ihn, viele besitzen ihn: den Badeschwamm. Doch Schwämme sind von weit höherem Nutzen: Sie produzieren eine Vielzahl bioaktiver Substanzen von großem pharmazeutischen Wert. Im Meer schützen sich die festgewachsenen Schwämme dadurch vor dem Gefressen- und Überwachsenwerden. Aber auch beim Kampf um neuen Lebensraum, zum Beispiel im dichtbesiedelten Korallenriff, werden die chemischen „Kampfstoffe“ eingesetzt (Abb. 1,2). Diese Substanzen können bisher jedoch nicht in großem Maßstab gewonnen und genutzt werden. Abhilfe können neue Methoden zur Kultivierung von Schwämmen im Meer und in Aquarien sowie zur Züchtung von Schwammzellen in der Petrischale oder im Bioreaktor leisten. Erstmals wird in einem bundesweiten Projekt die nachhaltige Nutzung mariner Schwämme in Zusammenarbeit mit internationalen Gruppen fokussiert. Durch die Bündelung und Vernetzung der Kompetenzen sollen die ersten Erfolge der am Forschungsvorhaben BIOTECmarin beteiligten Gruppen weiterentwickelt werden, Extrakte hinsichtlich der pharmazeutischen Produkte untersucht und biotechnologische Verfahren zur Produktion erarbeitet werden.
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