4 research outputs found
Silica nanoparticles and their interaction with cells : a multidisciplinary approach
Silica nanoparticles are increasingly used as drug delivery systems and for biomedical imaging.
Therapeutic and diagnostic agents can be incorporated into the silica matrix to improve the stability
and solubility of hydrophobic drugs in biological systems. However, the safety of silica
nanoparticles as drug carriers remains controversial. To date, no validated and accepted nanospecific
tests exist to predict the potentially harmful impact of these materials on the human body.
The mechanism proposed for hemolysis of unmodified silica nanoparticles is based on the electrostatic
interaction between the silanol surface groups and the quaternary ammonium in the choline
head group of the phospholipids. However, a detailed understanding of this process is missing.
In this thesis, different silica nanoparticles where synthesized, characterized, and tested in two cell
lines regarding viability and oxidative stress. Hemolysis was assessed using red blood cells. Furthermore,
the hemolytic mechanism of a chosen silica nanoparticle type was investigated in depth
using a biophysical chemistry approach. We used the dye-leakage assay, isothermal titration
calorimetry, solid state nuclear magnetic resonance, and flow cytometry to elucidate this mechanism.
Our results revealed that silica nanoparticles with a porous surface and negative surface charge
had the strongest impact on viability in a concentration dependent manner. This is in contrast to
non-porous silica nanoparticles. None of the studied particles caused oxidative stress in either cell
lines. Particles with a negative surface charge induced hemolysis. The mechanism responsible for
the hemolysis for silica nanoparticles had no electrostatic component. The nuclear magnetic resonance
data revealed no interaction with the choline group. However, nuclear magnetic resonance
data suggested the presence of faster tumbling species.
Our toxicological and mechanistic studies showed potential hazards of spherical amorphous silica
nanoparticles. Physico-chemical properties mediating toxicity in living cells were identified.
We propose that our standardized silica nanoparticles may serve as a readily available reference
material for nanotoxicological investigations. Mechanistic data did not support an electrostatic
interaction as postulated in the literature, but rather a strong adsorption process that may lead
to hemolysis. Furthermore, the presence of faster tumbling species suggested the formation of
smaller lipid bilayer structures upon silica nanoparticles exposure. Flow cytometry data revealed
that their size is about 100 nm. It remains to be proven if the bilayer wraps around the hemolytic
silica nanoparticles, if an exclusive formation of smaller species without wrapping is present, or
both of the aforementioned
Physiological parameters for Prognosis in Abdominal Sepsis ({PIPAS}) Study: a {WSES} observational study
Background: Timing and adequacy of peritoneal source control are
the most important pillars in the management of patients with
acute peritonitis. Therefore, early prognostic evaluation of
acute peritonitis is paramount to assess the severity and
establish a prompt and appropriate treatment. The objectives of
this study were to identify clinical and laboratory predictors
for in-hospital mortality in patients with acute peritonitis and
to develop a warning score system, based on easily recognizable
and assessable variables, globally accepted. Methods: This
worldwide multicentre observational study included 153 surgical
departments across 56 countries over a 4-month study period
between February 1, 2018, and May 31, 2018. Results: A total of
3137 patients were included, with 1815 (57.9\%) men and 1322
(42.1\%) women, with a median age of 47 years (interquartile
range [IQR] 28-66). The overall in-hospital mortality rate was
8.9\%, with a median length of stay of 6 days (IQR 4-10). Using
multivariable logistic regression, independent variables
associated with in-hospital mortality were identified: age > 80
years, malignancy, severe cardiovascular disease, severe chronic
kidney disease, respiratory rate 22 breaths/min, systolic
blood pressure 4 mmol/l. These variables were used to create the
PIPAS Severity Score, a bedside early warning score for patients
with acute peritonitis. The overall mortality was 2.9\% for
patients who had scores of 0-1, 22.7\% for those who had scores
of 2-3, 46.8\% for those who had scores of 4-5, and 86.7\% for
those who have scores of 7-8. Conclusions: The simple PIPAS
Severity Score can be used on a global level and can help
clinicians to identify patients at high risk for treatment
failure and mortality
Prolegomena zu einer Edition von Erasmus von Rotterdam "Scholia in Epistolas Hieronymi"
Zusammenfassung:
1515-16 erschien bei Johannes Froben in Basel die erste Gesamtausgabe der Werke des Kirchenvaters Hieronymus. Diese Edition, ein Meilenstein in der Geschichte der patristischen Editionen, entstand aus der Verschmelzung zweier ursprünglich unabhängiger Projekte: Der Basler Buchdrucker Johannes Amerbach hatte seit Ende der 1480er Jahre den Plan verfolgt, die vier grossen lateinischen Kirchenväter (Ambrosius, Augustinus, Hieronymus und Gregorius den Grossen) in zuverlässigen Gesamtausgaben zugänglich zu machen. Nach dem Erscheinen des Ambrosius und des Augustinus bereitete er ab 1507 die wesentlich kompliziertere Hieronymus-Ausgabe vor. Erasmus von Rotterdam anderseits plante seit 1500 eine Hieronymus-Edition. Im August 1514 schlossen sich dann Erasmus und Amerbachs Nachfolger Johannes Froben zusammen; das Ergebnis war die eingangs erwähnte Edition in neun Bänden. Erasmus war primär für die ersten vier Bände zuständig, welche die Briefe sowie die polemischen und apologetischen Schriften enthalten. Zu diesen Bänden verfasste er ausführliche Einleitungsbriefe sowie Inhaltsregesten (argumenta) sowie Erläuterungen (scholia) zu den einzelnen Werken. Darüber hinaus beriet er die Bearbeiter der Bände V–IX. Ausserdem steuerte er ein kritisches Werkverzeichnis sowie eine Biographie des Hieronymus bei.
Die nun auch online zugänglich gemachte Dissertation ist konzipiert als Vorarbeit und Grundlage zu einer Edition von Erasmus von Rotterdams Scholien innerhalb der Amsterdamer Erasmus-Gesamtausgabe ASD. Sie bietet nicht die dringend erwünschte erschöpfende Untersuchung von Hieronymus’ Einfluss auf Erasmus, ebenso wenig eine Untersuchung über den Inhalt, den Aufbau und die Absicht des Kommentars. Thema ist die Entstehung, die Aufnahme und die wiederholten Überarbeitungen der Hieronymus-Ausgabe und vor allem der Scholia. Da wir wohl über keine andere Edition des Erasmus so gut dokumentiert sind und weil die Edition nicht nur in Erasmus’ Leben, sondern auch in der Geschichte der Patristik einen wichtigen Platz einnimmt, schien es sinnvoll, ihre Genese und Rezeption exemplarisch nachzuzeichnen.
Nach der Einleitung, welche die Hieronymus-Ausgabe in einen grösseren Zusammenhang stellt, und einem Überblick über die bisher geleistete Forschung (Kap. I) folgt in Kap. II eine Zusammenstellung der umfangreicheren vor 1516 erschienenen Hieronymus-Editionen und ihres Verhältnisses zueinander. Auch diese dient dazu, unsere Ausgabe im historischen Umfeld zu situieren.
Das nächste Kapitel (III) befasst sich mit der Entstehungsgeschichte der ersten Auflage. In knapper Form wird Erasmus’ Beschäftigung mit und sein Verhältnis zu Hieronymus geschildert. Das Hauptgewicht liegt aber auf seiner Arbeit an der Edition. Die Vorbereitungen Amerbachs bzw. Frobens werden ebenfalls ausführlich dargestellt, da sie ganz wesentlich zur Qualität und dem Erfolg der Ausgabe beigetragen haben. Zu diesem Kapitel gehört Appendix I, welche Erasmus’ Scholia-Handschrift gewidmet ist. Die Geschichte der Handschrift, die daran gewandte Forschung, ihr Inhalt und Aufbau werden darin behandelt; daneben werden auch ein paar nicht zu den Scholia gehörige Fragmente ausgewertet.
In Kapitel IV wird sodann versucht, am Beispiel der Hieronymus-Edition die Vertriebsstrategien der Geschäftspartnerschaft Froben/Erasmus aufzuzeigen. Als Ergänzung dazu kann man Appendix VII über Holbeins Erasmus-Porträt in der Radnor Collection lesen.
Kapitel V gilt der Rezeption der Ausgabe von 1515 an, d.h. von dem Moment an, da ihr bevorstehendes Erscheinen weit herum bekannt wurde, und Erasmus’ Reaktion auf Lob und Kritik. Auch werden annotierte Exemplare aus dem Besitz bedeutender Theologen wie Luther, Zwingli und Bullinger vorgestellt. Appendix V behandelt den Index expurgatorius der katholischen Kirche von 1571 und bietet eine kritische Edition der die Hieronymus-Edition betreffenden Passagen.
Erst nach dem Echo auf die Ausgabe werden in Kapitel VI die weiteren von Erasmus besorgten Auflagen behandelt, da Erasmus bei seinen Neubearbeitungen oft auf geäusserte Kritik reagiert hat. Kapitel VII gehört mit Appendix II zusammen. Während die Appendix einen möglichst vollständigen chronologischen Katalog der Nachdrucke der Ausgabe enthält, sind diese Nachdrucke in Kapitel VII in zusammengehörigen Gruppen behandelt und als Zeugnisse für die Rezeption ausgewertet. Die in Kapitel VIII vorgestellten Übersetzungen sollen das Bild der Rezeption abrunden.
Kapitel IX schliesslich ist einem im allgemeinen eher mit wenig Respekt abgehandelten, aber äusserst nützlichen und vom Publikum hoch geschätzten Bestandteil der Ausgabe reserviert, nämlich den Indizes zu den verschiedenen Auflagen.
Summary:
In 1515-16, the first complete edition of the works of the Church Father St. Jerome was published by Johannes Froben in Basel. This edition, a milestone in the history of patristic editions, was the result of the merging of two originally independent projects: In Basel, from the late 1480ies the printer Johannes Amerbach had been realizing his idea of providing reliable complete editions of the four great Latin Fathers of the Church (Ambrose, Augustine, Jerome, and Gregory the Great). After the publication of Ambrose and Augustine, he embarked from 1507 on preparatory work for the edition of Jerome, which was considerably more complicated. On the other hand, Erasmus of Rotterdam had been planning an edition of Jerome ever since 1500. In 1514, Erasmus and Amerbach's successor, Johannes Froben, united their forces, the result being the edition mentioned above, in nine volumes. Erasmus was responsible primarily for the first four volumes containing the Letters as well as polemic and apologetic writings. Apart from elaborate introductions to these volumes, he wrote synopses (argumenta) of and annotations (scholia) on the single works. Moreover, he acted as advisor to the editors of vols. V-IX, and he contributed a critical catalogue of works as well as a biography of Jerome.
The thesis, now made accessible also online, has been conceived as a preliminary study and basis of an edition of the Scholia of Erasmus of Rotterdam in the Amsterdam edition of the works of Erasmus (ASD). It is neither the long wished-for comprehensive study of Jerome's influence of Erasmus nor an investigation of the contents, structure, and intention of the annotations. Its subject is the nascency, the reception, and the various revisions of the edition as a whole and most specifically of the Scholia. Since we are not nearly as well-documented on any other of Erasmus's editions and because this edition did not only play a crucial role in Erasmus's life, but also in the history of patristics, it seemed worthwhile to establish an exemplary account of its origin and and history.
Subsequent to the introduction, which puts the edition of Jerome in its larger context, and an overview of the research work done so far (chap. I), chap. II contains a compilation of the more extensive editions of Jerome published before 1516, and illustrates their interrelations. This account, too, serves to define the position of our edition in its historical context.
The next chapter (III) is an outline of the making of the first edition. Erasmus's work on, and relation to Jerome are characterized concisely. The focus, however, is on Erasmus's work on the edition. The preparatory work of Amerbach and Froben respectively is given ample attention as well, for it was constitutional for the quality and success of the edition. Appendix I, dedicated to the manuscript of Erasmus's Scholia, is to be read with this chapter. It recounts the history of the manuscript, the research dedicated to it, and its contents and structure; moreover several fragments not belonging to the Scholia are analysed and interpreted.
Following this, chap. IV is an attempt to illustrate, using the edition of Jerome as a paradigm, the marketing strategies of the business partnership Froben/Erasmus. It is complemented by Appendix VII about Holbein's portrait of Erasmus in the Radnor Collection.
Chapter V treats the response to the edition from 1515, viz. from the date when the news of its imminent publication had spread widely, and Erasmus's reaction to praise and criticism. Moreover it offers descriptions of annotated copies once in the ownership of eminent theologians such as Luther, Zwingli, and Bullinger. Appendix V deals with the Index expurgatorius of the Catholic Church of 1571, including a critical edition of the passages concerning the edition of Jerome.
So it is only after the response to the first edition that the later editions attended to by Erasmus are discussed in chapter VI, for Erasmus used to take into account critical comments in his revisions. Chapter VII is to be read with Appendix II, which contains as complete as possible a catalogue of the reprints of the edition in chronological order. This forms the basis for grouping them according to their interdependencies in chapter VII and analysing them as testimonies for the reception of the edition. The translations presented in chapter VIII serve to complete the reception history.
Finally, chapter IX is dedicated to a part of the edition not normally treated with great respect, but a very useful one and held in high esteem by the public, namely the indices to the various editions and impressions
