Walter Rummel (pharmacologist)

Walter Rummel

Walter Heinz Rummel (born October 23, 1921 in Freiburg im Breisgau ; † July 4, 2015 ) was a German doctor and pharmacologist . For 32 years he held the chair for pharmacology and toxicology at the Saarland University in Homburg .

Life

His parents were the music teacher Bruno Rummel and his wife Gertrud geb. Laternser. Walter attended the humanistic Berthold grammar school in Freiburg . As a member of the Association of German Catholic Youth , which was banned in 1938 , he was refused registration at a university. He therefore applied for training as a medical officer, began studying medicine at the Military Medical Academy in Berlin and continued it in Würzburg, Giessen, Freiburg and Tübingen. In Giessen and Würzburg he also took philosophical courses. In 1946 he passed the state examination and was awarded a doctorate degree with a dissertation “Contribution to the normal and pathological histology of the sympathetic cervical ganglia in humans” by the Freiburg pathologist Franz Büchner. med. PhD. In addition to pathology, he also worked at the Freiburg Physiological Institute with Paul Hoffmann . The Pharmacological Institute of the Medical Academy in Düsseldorf followed in 1947 , headed by Hellmut Weese and from 1951 by Fritz Hahn . One and a half years at the University of Bern were decisive for Rummel's future, namely at the Physiological Institute under Alexander von Muralt and at the Pharmacological Institute under Walther Wilbrandt . Above all, Wilbrandt's research on the permeability of biological membranes and membrane transport influenced him, already recognizable from the topic of his habilitation thesis 1952 "Energetics and Organization of Selective Permeability". In 1958 he was appointed to the chair in Homburg as the successor to Robert Domenjoz (1908–2000). 1962/1963 he was dean of the Homburg Medical Faculty. He turned down a call to Tübingen in 1970. Even after his retirement in 1990, he continued to live in Homburg. With his wife Auguste Amalie geb. Seitz, whom he married in 1947, he had three daughters and a son.

plant

After working on the active ingredient group of analeptics , Rummel's research on the absorption of iron , on other membrane transports and on the active ingredient group of laxatives have expanded pharmacological knowledge.

Analeptics

Rummel carried out these investigations under the direction of Fritz Hahn in Düsseldorf. In a review article Hahn included pentetrazole , nikethamide , strychnine , camphor and methylxanthines such as caffeine among the analeptics . All of them cause cramps in high doses. The Düsseldorf pharmacologists were primarily interested in the effect on the blood circulation and - with electroencephalography as a method - the sites of action for triggering convulsions. With pentetrazole, it was the brain. Pentetrazole is therefore used in animal epilepsy research . Apart from that, the analeptics are therapeutically abandoned except for the methylxanthines; they are also inhomogeneous in terms of the mechanisms of action and therefore obsolete as a classification unit.

Related to analeptics research is Rummel's later research, together with Joachim Knabe from the Institute for Pharmaceutical Chemistry at Saarland University, on differences in the effects of the enantiomers of barbiturates . Some did not act as a sleep aid or as an anticonvulsant, but on the contrary act as an anticonvulsant. The differences in activity indicated the existence of specific receptors for these substances.

Iron absorption

Rummel's works on the absorption of iron from the digestive tract are of lasting importance . In his first two publications, he, now an independent scientist, used the radioactive iron isotope ⁵⁹ Fe to show that phosphates inhibit absorption, whereas complexing agents such as ascorbic acid and cysteine ​​promote them. The role of complexing agents has been carefully examined. Some, like ascorbic acid and the amino acid cysteine , also act as reducing agents , reducing Fe (III), trivalent iron, to Fe (II), divalent iron. When thinking about iron complexes, it seemed interesting to Rummel to make a complex of iron (II) sulfate with a non-reducing amino acid, namely with glycine . He was granted a patent for this in 1955 in both Germany and the USA . The Fe (II) glycine sulfate complex was developed by Dr. Schwarz KG in Monheim am Rhein , today part of the UCB Group , launched on the market as ferro sanol® . Ferrosanol is still the most frequently prescribed iron preparation for the treatment of iron deficiency anemia and the most frequently prescribed anti-anemic in general . In Germany, 34.4 million daily doses were prescribed in 2009 .

Rummel then delved into the details of iron absorption. Proteins were critically involved. One, protein 2 , was decreased in mice with anemia due to genetic defects. It was not necessary to take up the iron from the intestinal lumen into the epithelial cells of the intestinal mucosa , but rather to leave the epithelial cells on the opposite side facing the blood. In both cases, both on the intestinal lumen side and on the opposite side, the iron passed the cell membrane as Fe (II), not as Fe (III). In 1973 Rummel summarized the subject with his student Wolfgang Forth , and in 1995 with his student Peter Wollenberg in overview articles. It was left to later methods to molecularly identify the transport proteins and the iron-reducing and oxidizing enzymes.

Vanadium in sea squirts

As has been known since the beginning of the 19th century, sea ​​squirts (ascidia) contain high concentrations of the chemical element vanadium . In some of your blood cells it is enriched a million times over in seawater. The animals have several vanadium-binding proteins, so-called vanabins. Rummel investigated the enrichment with a group of scientists around the biochemist and marine biologist Hans-Joachim Bielig (* 1912) at the Naples Zoological Station . The animals ingested the vanadium through their gill intestines and the accumulation was an active transport . It was precisely its remoteness that made the topic - alongside ancient sites such as Paestum - attractive to hype. To date (2011) the physiological function of vanadium in sea squirts is unknown. The assumption that it serves to transport oxygen like iron in hemoglobin has proven to be wrong.

laxative

They are among the first substances whose pharmacological effect was noticed by humans and they are of great practical importance. The Rummels group in Homburg had vague ideas earlier, they "irritated" the intestinal mucous membrane and thus stimulated the intestinal peristalsis , clarified and the current classification into lubricants such as viscous paraffin , osmotic substances such as lactulose , swelling agents such as flaxseed and finally - a name von Rummels Gruppe - antiabsorptive-secretagogic substances like castor oil , the anthraquinones and the bisacodyl established.

For their first investigation, Forth, Rummel, and their co-workers primarily used bisacodyl. They concluded: “The laxatives that were the subject of this investigation are included in the group of laxatives that attack the colon. The effect should be based on a stimulation of the motor skills. It is not clear whether it is direct or indirect excitation. ... The most important finding for elucidating the mechanism of action of these substances is the fact that they inhibit the absorption of salt and water. The colon proved to be several times more sensitive. In addition, in contrast to the behavior on the jejunum, there was not only an inhibition of Na and water absorption in the colon , but in the case of higher, but certainly in the therapeutic range, concentrations of bisacodyl z. B. to a reversal of the net flux, ie to a net outflow into the intestine. ... Finally, it seems advisable to us to include the group of substances among the laxatives which, in high dilution, inhibit or reverse the net transport of sodium and water from the intestine to the blood, according to their special mechanism of action as laxatives with an anti-resorptive and secretion - promoting effect to differentiate primarily osmotically or primarily motor-acting substances. ”Today, research is being carried out into the extent to which an inhibition of the sodium-potassium pump , prostaglandins , platelet-activating factor or nitric oxide are involved in the anti-absorptive-secretagogical effect.

Teaching and professional policy

In 1975 the 11th edition of “General and Systematic Pharmacology and Toxicology” was published for the first time, written by Wolfgang Forth, the Würzburg toxicologist Dietrich Henschler and Rummel, and published today (2015) by others.

Rummel was a member of the Drugs Commission of the German Medical Association from 1966 to 1993 , from 1969 to 1993 as a board member, from 2003 as an honorary member. He was a founding member of the ethics committee of the Saarland Medical Association, a member of the Senate of the German Research Foundation and a member of the Medicines Commission of the Grand Duchy of Luxembourg .

student

The following scientists completed their habilitation in Homburg during Rummel's time or achieved leading academic positions after their work there (with the year they entered the institute):

• Karl Pfleger (1958), later head of a newly established department for toxicology and biochemical pharmacology
• Ilmar Jurna (1959)
• Ernst Seifen (1959), later Professor in the Department of Pharmacology and Toxicology at the University of Arkansas in Little Rock , Arkansas
• Wolfgang Forth (1960), later professor at the Ruhr University Bochum and the Ludwig Maximilians University in Munich
• Horst Paul Büch (1962)
• Josef Baldauf (1962)
• Gerfried Nell (1969)
• Helmut A. Hübers (1970), later at the Department of Hematology at the University of Washington in Seattle , Washington
• Hans Hilarius Maurer (1979), later Pflegeer's successor as head of the so-called Department of Experimental and Clinical Toxicology
• Robert J. Bridges (1981), later Professor of Physiology and Biophysics at the Rosalind Franklin University of Medicine and Science in Chicago , Illinois
• Martin Diener (1986), later head of the Institute for Veterinary Physiology and Biochemistry at the Justus Liebig University in Giessen

Web link

Ulrich Boehm, Adolfo Cavalié, Veit Flockerzi, Hans H. Maurer, Wolfgang Müller: In memoriam Prof. Dr. Walter Rummel. And: Klaus Starke: In memoriam Walter Rummel - a friend's memory. In: Biospektrum 21, 2015, S: 659-661. Digitized. Retrieved December 1, 2015.

Individual evidence

1. ^ Walter Heinz Rummel: Obituary notice
2. ↑ Veit Flockerzi and Wolfgang Müller: Prof. Dr. Walter Rummel 80 years. In: Saarländisches Ärzteblatt. 2001; 10: 28-29.
3. ^ F. Hahn: Analeptics. In: Pharmacological Reviews . 1960; 12: 447-530.
4. ↑ J. Knabe, W. Rummel, HP Büch, N. Franz: Optically active barbiturates. In: drug research . 1978; 28: 1048-1056.
5. ↑ Hair Eddin Jacobi, Karl Pfleger and Walter Rummel: influence of phosphates to the enteral absorption of physiological amounts of iron. In: Natural Sciences . 1956; 43: 354-355.
6. ↑ H. Jacobi, K. Pfleger, W. Rummel: Complexing agents and active iron transport through the intestinal wall. In: Naunyn-Schmiedeberg's archive for experimental pathology and pharmacology . 1956; 229: 198-206.
7. ^ Klaus Mengel: Antianemics. In: Ullrich Schwabe and Dieter Paffrath (eds.): Drug Ordinance Report 2010. Berlin, Springer-Verlag 2010, pp. 291-301. ISBN 978-3-642-13379-4 .
8. ↑ Helmut Huebers, Eiko Huebers, Wolfgang Forth, Walter Rummel: Iron absorption and iron-binding proteins in intestinal mucosa of mice with sex-linked anemia. In: Hoppe-Seyler's Journal for Physiological Chemistry . 1973; 354: 1156-1158.
9. ^ P. Wollenberg, W. Rummel: Dependence of intestinal iron absorption on the valency state of iron. In: Naunyn-Schmiedeberg's Archives of Pharmacology. 1987; 336: 578-582.
10. ^ Peter Wollenberg, Rolf Mahlberg, Walter Rummel: The valency state of absorbed iron appearing in the portal blood and ceruloplasmin substitution. In: Biological Metals. 1990; 3: 1-7.
11. ^ W. Forth, W. Rummel: Iron Absorption. In Physiological Reviews . 1973; 53: 724-792.
12. ^ Walter Rummel, Peter Wollenberg: Iron: abundant, but difficult to find. In: Hermann Josef Haas (Hrsg.): Mechanisms of the transport of minerals and trace elements. Stuttgart, Wissenschaftliche Verlagsgesellschaft 1995, pp. 73–82.
13. ^ P. Wollenberg: Iron - Pharmacotherapy of iron deficiency. In: K. Aktories, U. Förstermann, F. Hofmann and K. Starke (eds.): General and special pharmacology and toxicology. 10th edition, Munich, Elsevier GmbH 2009, pp. 741-751. ISBN 978-3-437-42522-6 .
14. ^ HJ Bielig, K. Pfleger, W. Rummel, M. de Vincentius: Beginning of the accumulation of vanadium during the early development of the ascidian Phallusia mamillata Cuvier. In: Nature. 1963; 197: 1223-1224.
15. ↑ W. Rummel, H.-J. Bielig, W. Forth, K. Pfleger, W. Rüdiger, E. Seifen: Absorption and accumulation of vanadium in tunicates. In: Proteides of the Biological Fluids. 1966; 14: 205-210.
16. ↑ Tatsuya Ueki, Michibata Hitoshi: Molecular mechanism of the transport and reduction pathway of vanadium in ascidians. In: Coordination Chemistry Reviews . 2011.
17. ↑ H. Kilbinger: Pharmaceuticals for influencing the functions of the stomach, small and large intestines. In: K. Aktories, U. Förstermann, F. Hofmann, K. Starke (eds.): General and special pharmacology and toxicology. 10th edition, Munich, Elsevier GmbH 2009, pp. 547-577. ISBN 978-3-437-42522-6 .
18. ↑ W. Forth, W. Rummel, J. Baldauf, H. Andres, H. Wilbert: Water and electrolyte movement in the small and large intestine under the influence of laxatives, a contribution to the clarification of their mechanism of action. In: Naunyn-Schmiedebergs Archive for Pharmacology and Experimental Pathology. 1966; 254: 18-32.
19. ^ G. Nell, W. Rummel: Action mechanisms of secretagogue drugs. In: TZ Csáky (Ed.): Pharmacology of Intestinal Permeation II. Handbook of Experimental Pharmacology. Volume 70 / II. Berlin, Springer-Verlag 1984, pp. 461-508. ISBN 3-540-13101-9 .
20. ↑ K. Aktories , U. Förstermann , F. Hofmann , K. Starke (eds.): General and special pharmacology and toxicology. 10th edition, Elsevier GmbH, Munich 2009, ISBN 978-3-437-42523-3 .
21. ^ Jürgen Lindner, Heinz Lüllmann : Pharmacological institutes and biographies of their directors. Editio Cantor Verlag, Aulendorf 1996.