Philosophy of nature and organism's autonomy: on Hegel, Plessner and Jonas' theories of living beings.

Following the revival in the last decades of the concept of "organism", scholarly literature in philosophy of science has shown growing historical interest in the theory of Immanuel Kant, one of the "fathers" of the concept of self-organisation. Yet some recent theoretical developments suggest that self-organisation alone cannot fully account for the all-important dimension of autonomy of the living. Autonomy appears to also have a genuine "interactive" dimension, which concerns the organism's functional interactions with the environment and does not simply derive from its internal organisation. Against this background, we focus on a family of natural philosophical approaches that historically have already strongly taken in account this aspect of autonomy, notably going beyond Kant's perspective on self-organisation. We thus review Hegel, Plessner, and Jonas' different perspectives on living beings, focussing in particular on four points: the distinction between organic and inorganic, the theory of biological organisation, the processuality of the living, and the "boundary" between inside and outside, through which the organism establishes its relationship to the environment. We, then, compare the three perspectives on these four points, and finally address the question of what advantages their contribution present-especially compared to Kant's theory-with respect to the topic of organism's autonomy. This could help-we hope-to better understand what is at the stake still today.

Staged ultrasound-guided liposuction for hidden arteriovenous fistulas in obese patients.

BACKGROUND: In obese patients with end stage renal disease, puncturing matured arteriovenous fistulas (AVF) that run deep under the skin surface may prove difficult. To achieve reliable puncturability, there are several surgical solutions. Superficialization with mobilization is common. With some newer options (lipectomy and liposuction) subcutaneous adipose tissue is surgically reduced. There are only a few authors who have published their experience with liposuction and we want to add our own results. PATIENTS AND METHODS: We report our experience with ultrasound-guided liposuction (USGL). We introduce liposuction cannulas via small incisions to reduce the subcutaneous adipose tissue overlying the planned cannulation zones under ultrasound control using tumescent anaesthesia till the prospective needle access segments become easily palpable. So far, we have used this technique for cephalic forearm and upper arm fistulas only. Furthermore, we review the relevant literature. RESULTS: From February 2014 through November 2016, six patients were treated using USGL. Their body mass indices ranged from 30.8 to 53.8 kg/m2 (mean 37.6). The mean depths of the AVFs beneath the skin surface were 13.3 (8-20) mm before and 5.1 (3.5-6) mm after surgery. The mean time of the procedure was 15 minutes. There were no postoperative complications. In five patients, the AVFs could reliably be punctured after three weeks. One patient is not yet on dialysis. During the follow-up period of 24 (11-43) months, all six AVFs remained primarily patent. In the literature, we found nine reports on altogether 81 patients undergoing USGL. Almost all noteworthy complications occurred only after ultrasound-powered liquefaction of adipose tissue, which was only used by a single investigator. CONCLUSIONS: USGL is a method that can be learned easily, is minimally invasive, seems to be safe, and requires only short operation times.

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics.

The amide moiety of peptides can be replaced for example by a triazole moiety, which is considered to be bioisosteric. Therefore, the carbonyl moiety of an amino acid has to be replaced by an alkyne in order to provide a precursor of such peptidomimetics. As most amino acids have a chiral center at Cα, such amide bond surrogates need a chiral moiety. Here the asymmetric synthesis of a set of 24 N-sulfinyl propargylamines is presented. The condensation of various aldehydes with Ellman's chiral sulfinamide provides chiral N-sulfinylimines, which were reacted with (trimethylsilyl)ethynyllithium to afford diastereomerically pure N-sulfinyl propargylamines. Diverse functional groups present in the propargylic position resemble the side chain present at the Cα of amino acids. Whereas propargylamines with (cyclo)alkyl substituents can be prepared in a direct manner, residues with polar functional groups require suitable protective groups. The presence of particular functional groups in the side chain in some cases leads to remarkable side reactions of the alkyne moiety. Thus, electron-withdrawing substituents in the Cα-position facilitate a base induced rearrangement to α,ß-unsaturated imines, while azide-substituted propargylamines form triazoles under surprisingly mild conditions. A panel of propargylamines bearing fluoro or chloro substituents, polar functional groups, or basic and acidic functional groups is accessible for the use as precursors of peptidomimetics.

Structure-Activity Relationship of Propargylamine-Based HDAC Inhibitors.

As histone deacetylases (HDACs) play an important role in the treatment of cancer, their selective inhibition has been the subject of various studies. These continuous investigations have given rise to a large collection of pan- and selective HDAC inhibitors, containing diverse US Food and Drug Administration (FDA)-approved representatives. In previous studies, a class of alkyne-based HDAC inhibitors was presented. We modified this scaffold in two previously neglected regions and compared their cytotoxicity and affinity toward HDAC1, HDAC6, and HDAC8. We were able to show that R-configured propargylamines contribute to increased selectivity for HDAC6. Docking studies on available HDAC crystal structures were carried out to rationalize the observed selectivity of the compounds. Substitution of the aromatic portion by a thiophene derivative results in high affinity and low cytotoxicity, indicating an improved drug tolerance.