Platons Biologie und Krankheitslehre

Die Aussagen Platons zur Biologie und Medizin wie sie im Timaeus dargelegt sind, haben in der Vergangenheit unterschiedliche Bewertungen erfahren. Die im Dialog präsentierten Vorstellungen zur Anatomie, Histologie und Nosologie wurden in der Vergangenheit teilweise vollständig abgelehnt, andererseits aber auch als naturwissenschaftlich im modernen Sinn interpretiert. Obwohl in den letzten Jahren ein erhöhtes Interesse an diesem Dialog zu beobachten ist, fehlen systematische Untersuchungen zu dieser Thematik. In vorliegender Dissertationsschrift wird der Versuch unternommen, die Aussagen Platons durch Vergleich mit zeitgenössischen Erkenntnissen zur Biologie und Medizin auf ihre wissenschaftliche Qualität hin zu prüfen und zudem ihre etwaigen Abhängigkeiten von der vorsokratischen Naturphilosophie und den medizinischen Erkenntnissen des 5. und 4. vorchristlichen Jahrhunderts aufzuzeigen. Platons Schrift steht in Abhängigkeit der περὶ φύσεως Tradition der vorsokratischen Naturphilosophie. Die Methode ist was die Anatomie betrifft deskriptiv, hinsichtlich der physiologischen und nosologischen Konzepte aber weitgehend spekulativ und deduktiv; bis auf eine Ausnahme – die Blutgerinnung – werden keine wissenschaftlichen Versuche erwähnt, die geeignet wären im Sinne eines induktiven Schlusses Hypothesen zu generieren. Modern ist sein Konzept des εἰκὼς λόγος (Aussage mit hohem Wahrscheinlichkeitsgehaltes), das an das Prinzip der Falsifizierbarkeit als essentiellem Bestandteil einer naturwissenschaftlichen Erkenntnis erinnert. Ein nicht hoch genug einzuschätzendes Verdienst Platons ist die Einführung der Mathematik in die biologischen Wissenschaften. Sein Konzept, Eigenschaften organischer Substanzen aus der geometrischen Struktur der zugrundeliegenden molekularen Körper abzuleiten mutet geradezu modern an. Obwohl erst Aristoteles den Begriff der Gewebe exakt erarbeitet hat, finden wird ihn schon bei Platon vorgezeichnet, der seinerseits in Abhängigkeit von Empedokles und Anaxagoras steht. Platon gibt eine überraschend detailgerechte Darstellung der Verteilung der Muskulatur am Skelettsystem und der topographisch-anatomischen Verhältnissen an den Akren. In Timaeus werden anatomische und physiologische Fakten zu den Atemwegen, dem Zentralnervensystem, Gefäßsystem, Abdominal- und Geschlechtsorganen präsentiert, wobei die Aussagen zur topographischen Anatomie der Atemwege den größten Raum einnehmen. Mit dem Bild der Fischreuse (ὁ κύρτος) wird erstmals in der abendländischen naturwissenschaftlichen Tradition ein anschauliches Bild des Naso-, Oro- und Hypopharynx geliefert. Seine Verbindung der Physiologie der Atmung mit Aussagen zur Ernährungsphysiologie und Stoffwechsel ist sehr stark von Konzepten der westgriechischen medizinischen Schulen beeinflusst, zeigt aber auch bereits eine Nähe zu modernen zeitgenössischen Konzepten: so können wir z.B. im Timaeus eine erste Formulierung des ersten Hauptsatzes der Wärmelehre finden. Platons Aussagen zur Anatomie des Zentralnervensystems sind einerseits oberflächlich, andererseits finden wird erstmalig einen Hinweis auf die Bedeutung der Zwischenwirbelscheiben für die Beweglichkeit der Wirbelsäule und eine Erwähnung des Liquor cerebrospinalis. Die topographisch-anatomischen Aussagen zum Herzkreislaufsystem zeichnen sich ebenfalls durch eine gewisse Einfachheit aus. Es werden im Wesentlichen nur die Aorta abdominalis und Vena cava inferior beschrieben. Platon gibt aber auch eine anschauliche Beschreibung der Kreuzung der Gefäße im Halsbereich, die allerdings vor ihm schon Diogenes von Apollonia, Synennesis und der Autor der Schrift de morbis I aus dem CH gesehen haben. Die physiologische Bedeutung des Herzkreislaufsystems für die Substratverteilumg im Körper ist richtig erkannt worden und von Platon in einem komplexen Konzept, das die Atmung in den Mittelpunkt der Betrachtung stellt, formuliert worden. Auch Platons Vorstellungen zum Oberbauchsitus beschränken sich auf die Beschreibung der Lage der Leber, Milz und des Omentum majus, dessen Funktion bei pathologischen Prozessen im Abdomen er erahnt. Die Niere wird nicht erwähnt, seine weitgehend falschen Vorstellungen zum Verlauf des Samenleiters sind von der enkephalo-myelogenen Samenlehre geprägt. Platons Nosologie steht in der Tradition der Krankheitslehren seiner Zeitgenossen wie z.B. des Dexippos von Kos, besonders aber auch der westgriechischen Medizin und hier wiederum des Philistion von Lokroi. In ihrer Komplexität gehen seine Theorien allerdings weit über die seiner Vorgänger hinaus. Zudem findet sich meines Erachtens im Dialog eine Auseinandersetzung mit dem Autor de morbo sacro aus dem CH um die Bezeichnung der Epilepsie als heilige Erkrankung. An speziellen Krankheitsbildern finden wir eine Beschreibung der Leberzirrhose, der Splenomegalie, Gangän und von Gerinnungsstörungen, die teilweise auch heutigen Vorstellungen entsprechen. Modern ist seine Vorstellung der somatischen Grundlage psychischer Erkrankungen. Platons therapeutische Vorstellungen zielen auf eine Wiederherstellung der Symmetrie von Körper und Geist durch Modifikation des Lebensstils; eine medikamentöse Therapie soll nur in Ausnahmefällen Verwendung finden.Platon’s statements concerning biology and medicine, like they are presented in his Timaeus, have been evaluated differently in the past. More than once the statements he made in his dialogue about anatomy, histology and nosology have been dismissed completely, yet also interpreted as “scientific“ in the modern sense. Even though one could witness a growing interest in his dialogue in the last few years, the thematic is still missing thorough systematic examination. The purpose of this dissertation is to try to examine the scientific quality of Platon’s statements through comparison with present-day knowledge of biology and medicine, and also to show any possible connections to the pre-Socratic natural philosophy and the medical knowledge of the fifth and fourth century BC. Platon’s method is mostly deductive; if one ignores the one exception, the blood coagulation, there are no scientific experiments mentioned that could be used to generate hypotheses through inductive reasoning. His concept of εἰκὼς λόγος (a statement with a high probability) which reminds one of the principle of falsifiability as an essential part of natural scientific knowledge is quite modern, though. One cannot overrate Platon’s contribution for including mathematics in biological sciences either. How modern his concept of deducing characteristics organic substances show from geometric shapes and structures sounds! Even though it was Aristotle who coined the term tissue first, we can find traces o fit in Platon’s work, which, in turn, was influenced by Empedokles and Anaxagoras. Very detailed is Platon’s description of the muscle’s arrangement at the skeletal frame and the topographical-anatomical ratio at the acra. The Timaeus presents anatomical and physiological facts concerning the respiratory system, the central nervous system, the vascular system, the abdominal organ and sex organs, with his observations about the respiratory system’s topographical anatomy filling the lion’s share of his dialogue. He is the first in the occidental tradition of natural sciences to present a clear illustration of the naso-, oro- and hypopharynx with the picture of ἐγκύρτια. His connection of the physiology of the respiration with statements about the nutrition physiology is strongly influenced by the medical schools of Western Greece, yet they also show some correspondence to modern-day concepts: i.e. already in Timaeus a forerunner of the first law of thermodynamics can be found. His statements concerning the anatomy of the central nervous system are superficial, but also give a first reference about the role the intervertebral disc plays for the flexibility of the spine as well as a mention of the liquor cerebrospinalis. When it comes to his statements concerning the topographical anatomy of the cardiovascular system, they can be characterized by their simplicity, as all they primarily describe are the aorta abdominalis and the vena cava inferior. Platon does provide his readers with a detailed description of the vascular junctions in the neck area, even though it has to be noted that Diogenes of Apollonia, Synessesis and the author of the de morbis I from the HC had already done that before him. He is right with his remark about the physiological importance the cardiovascular system plays for the substrate allocation in the body, which he formulated in a complex concept that centres on the respiration. Platon’s perception of the topographical anatomy of the epigastria is limited to him describing the location of the liver and the spleen. He also mentions the omentum majus and accomplishes to guess the role it plays in pathological processes of the abdomen. Yet he fails to mention the kidneys, and his false accounts of the spermatic duct’s run have been heavily influenced by the enkephalo-myelogene theory of spermatogenesis. The nosology coined by Platon stands within the tradition of his contemporary’s pathology, especially the medical science of Western Greece and Philistion from Lokroi, even though his accounts are much more complex as a whole. Furthermore, in my opinion, one can find a debate with the author of the de morbo sacro from the CH concerning epilepsy as some kind of sacred disease. Certain clinical pictures he describes show the reader the cirrhosis of the liver, splenomegaly, gangrene and the blood-clotting disorder; some of his accounts even match today’s knowledge of these diseases. Especially modern is also his idea that mental illnesses have somatic causes. When it comes to therapy, Platon aims to re-establish the symmetry of body and mind through modification of one’s lifestyle; only in exceptional cases drug therapies should be used

Ornipressin in the treatment of functional renal failure in decompensated liver cirrhosis

In 11 patients with decompensated cirrhosis and deteriorating renal function, the effect of the vasoconstrictor substance 8-ornithin vasopressin (ornipressin; POR 8; Sandoz, Basel, Switzerland) on renal function, hemodynamic parameters, and humoral mediators was studied. Ornipressin was infused at a dose of 6 IU/h over a period of 4 hours. During ornipressin infusion an improvement of renal function was achieved as indicated by significant increases in inulin clearance (+65%), paraaminohippuric acid clearance (+49%), urine volume (+45%), sodium excretion (+259%), and fractional elimination of sodium (+130%). The hyperdynamic circulation was reversed to a nearly normal circulatory state. The increase in systemic vascular resistance (+60%) coincided with a decrease of a previously elevated renal vascular resistance (-27%) and increase in renal blood flow (+44%). The renal fraction of the cardiac output increased from 2.3% to 4.7% (P less than 0.05). A decline of the elevated plasma levels of noradrenaline (2.08-1.13 ng/mL; P less than 0.01) and renin activity (27.6-14.2 ng.mL-1.h-1; P less than 0.01) was achieved. The plasma concentration of the atrial natriuretic factor increased in most of the patients, but slightly decreased in 3 patients. The decrease of renal vascular resistance and the increase of renal blood flow and of the renal fraction of cardiac output play a key role in the beneficial effect of ornipressin on renal failure. These changes develop by an increase in mean arterial pressure, the reduction of the sympathetic activity, and probably of an extenuation of the splanchnic vasodilation. A significant contribution of atrial natriuretic factor is less likely. The present findings implicate that treatment with ornipressin represents an alternative approach to the management of functional renal failure in advanced liver cirrhosis

William Harveys "Exercitatio anatomica de motu cordis et sanguinis in animalibus"

Harveys Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus gilt als eines der bedeutendsten wissenschaftlichen Werke der Frühen Neuzeit. Es ist zu einer Zeit entstanden, da sich die naturwissenschaftliche Forschung vom übermächtigen Einfluss des Artistoteles und seiner Teleologie zu lösen versuchte und sich, wie es Francis Bacon forderte, von den Finalursachen ab- den Gesetzmäßigkeiten der Materie zuwandte. Vorliegende Dissertation bietet erstmals einen kritischen Text der Erstausgabe mit Übersetzung und Zeilenkommentar. Zudem wurde die Arbeitsweise Harveys genauer untersucht. Es konnte gezeigt werden, dass in De Motu Cordis neben starken teleologischen Aspekten im Sinne eines konservativen Aristotelismus besonders auch die induktive Methode Bacons und der neuen aristotelischen Schule Paduaner Prägung zur Anwendung kamen und erstmals in den biologischen Wissenschaften und der Medizin quantitative Betrachtungen und Analysen heranzgezogen wurden, die erst die revolutionierenden neuen Vorstellungen zur Kreislaufphysiologie ermöglichten.Harvey’s „Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus“ is known as one of the most important scientific works of the Early Modern Age. It was composed in a time when attempts were made to disengage natural scientific research from Aristotle’s ubiquitous influence, and, like Francis Bacon demanded, to turn away from final causes towards natural laws of matter. This dissertation presents a critical text of Harvey’s first edition including a translation and line commentary. Furthermore, it examines Harvey’s working method. It shows that in “De Motu Cordis” the inductive method of Bacon and the new Aristotelian school of Padua were applied in combination with strong teleological aspects for which a conservative Aristotelianism is known. It was the first time that quantitative considerations and analyses were carried out in biological sciences and medicine, which revolutionised ideas held in physiology of blood circulation

Evaporation of free water causes concentrational alkalosis in vitro

BACKGROUND The development of metabolic alkalosis was described recently in patients with hypernatremia. However, the causes for this remain unknown. The current study serves to clarify whether metabolic alkalosis develops in vitro after removal of free water from plasma and whether this can be predicted by a mathematical model. MATERIALS AND METHODS Ten serum samples of healthy humans were dehydrated by 29 % by vacuum centrifugation corresponding to an increase of the contained concentrations by 41 %. Constant partial pressure of carbon dioxide at 40 mmHg was simulated by mathematical correction of pH [pH(40)]. Metabolic acid-base state was assessed by Gilfix' base excess subsets. Changes of acid-base state were predicted by the physical-chemical model according to Watson. RESULTS Evaporation increased serum sodium from 141 (140-142) to 200 (197-203) mmol/L, i.e., severe hypernatremia developed. Acid-base analyses before and after serum concentration showed metabolic alkalosis with alkalemia: pH(40): 7.43 (7.41 to 7.45) vs 7.53 (7.51 to 7.55), p = 0.0051; base excess: 1.9 (0.7 to 3.6) vs 10.0 (8.2 to 11.8), p = 0.0051; base excess of free water: 0.0 (- 0.2 to 0.3) vs 17.7 (16.8 to 18.6), p = 0.0051. The acidifying effects of evaporation, including hyperalbuminemic acidosis, were beneath the alkalinizing ones. Measured and predicted acid-base changes due to serum evaporation agreed well. CONCLUSIONS Evaporation of water from serum causes concentrational alkalosis in vitro, with good agreement between measured and predicted acid-base values. At least part of the metabolic alkalosis accompanying hypernatremia is independent of renal function

Acid–base status and its clinical implications in critically ill patients with cirrhosis, acute-on-chronic liver failure and without liver disease

Abstract Background Acid–base disturbances are frequently observed in critically ill patients at the intensive care unit. To our knowledge, the acid–base profile of patients with acute-on-chronic liver failure (ACLF) has not been evaluated and compared to critically ill patients without acute or chronic liver disease. Results One hundred and seventy-eight critically ill patients with liver cirrhosis were compared to 178 matched controls in this post hoc analysis of prospectively collected data. Patients with and without liver cirrhosis showed hyperchloremic acidosis and coexisting hypoalbuminemic alkalosis. Cirrhotic patients, especially those with ACLF, showed a marked net metabolic acidosis owing to increased lactate and unmeasured anions. This metabolic acidosis was partly antagonized by associated respiratory alkalosis, yet with progression to ACLF resulted in acidemia, which was present in 62% of patients with ACLF grade III compared to 19% in cirrhosis patients without ACLF. Acidemia and metabolic acidosis were associated with 28-day mortality in cirrhosis. Patients with pH values < 7.1 showed a 100% mortality rate. Acidosis attributable to lactate and unmeasured anions was independently associated with mortality in liver cirrhosis. Conclusions Cirrhosis and especially ACLF are associated with metabolic acidosis and acidemia owing to lactate and unmeasured anions. Acidosis and acidemia, respectively, are associated with increased 28-day mortality in liver cirrhosis. Lactate and unmeasured anions are main contributors to metabolic imbalance in cirrhosis and ACLF

The SPOC proteins DIDO3 and PHF3 co-regulate gene expression and neuronal differentiation

Abstract Transcription is regulated by a multitude of activators and repressors, which bind to the RNA polymerase II (Pol II) machinery and modulate its progression. Death-inducer obliterator 3 (DIDO3) and PHD finger protein 3 (PHF3) are paralogue proteins that regulate transcription elongation by docking onto phosphorylated serine-2 in the C-terminal domain (CTD) of Pol II through their SPOC domains. Here, we show that DIDO3 and PHF3 form a complex that bridges the Pol II elongation machinery with chromatin and RNA processing factors and tethers Pol II in a phase-separated microenvironment. Their SPOC domains and C-terminal intrinsically disordered regions are critical for transcription regulation. PHF3 and DIDO exert cooperative and antagonistic effects on the expression of neuronal genes and are both essential for neuronal differentiation. In the absence of PHF3, DIDO3 is upregulated as a compensatory mechanism. In addition to shared gene targets, DIDO specifically regulates genes required for lipid metabolism. Collectively, our work reveals multiple layers of gene expression regulation by the DIDO3 and PHF3 paralogues, which have specific, co-regulatory and redundant functions in transcription