Antiviral 6-amino-quinolones: molecular basis for potency and selectivity

Structural modifications introduced in 6-amino-quinolones to increase antiviral activity can strongly affect cytotoxicity to host cells. By competition to Tat-TAR complex and binding experiments to viral and cellular DNA and RNA structures, we show that the nature of the substituent at position 7 modifies drug affinity and specificity for the nucleic acid. Interestingly, the basicity of the above substituent modulates chelation of the quinolone template to magnesium ions, which, in turn, critically affects the potency and target selectivity in the antiviral quinolone family.     

How Do General Practitioners Conceptualise Advance Care Planning in Their Practice? A Qualitative Study

ObjectivesTo explore how GPs conceptualise advance care planning (ACP), based on their experiences with ACP in their practice.MethodsFive focus groups were held with 36 GPs. Discussions were analysed using a constant comparative method.ResultsFour overarching themes in the conceptualisations of ACP were discerned: (1) the organisation of professional care required to meet patients’ needs, (2) the process of preparing for death and discussing palliative care options, (3) the discussion of care goals and treatment decisions, (4) the completion of advance directives. Within these themes, ACP was both conceptualised in terms of content of ACP and/or in terms of tasks for the GP. A specific task that was mentioned throughout the discussion of the four different themes was (5) the task of actively initiating ACP by the GP versus passively waiting for patients’ initiation.ConclusionsThis study illustrates that GPs have varying conceptualisations of ACP, of which some are more limited to specific aspects of ACP. A shared conceptualisation and agreement on the purpose and goals of ACP is needed to ensure successful implementation, as well as a systematic integration of ACP in routine practice that could lead to a better uptake of all the important elements of ACP.     

Deutungsversuch zur Nahrungsaufnahme eines schnabelverletzten Austernfischers(Haematopus ostralegus)

Zusammenfassung Eine MitteilungFlints über die Nahrungsaufnahme eines schnabelverletzten Austernfischers (Gefangenschaftsvogel) gab Anlaß zu einigen Gedanken darüber, welche angeborenen Verhaltensweisen dem Vogel bei der Erfindung seiner neuen Methode von Nutzen gewesen sein können. — So wird das Aufspießen von Brocken in der Futterschüssel mit dem Erbeuten von Muscheln und Krabben durch Aufspießen verglichen und das Herausschleudern des Bissens als Versuch gedeutet, einen Fremdkörper loszuwerden. Das beachtliche Hinstoßen des Brockens zu einer Rinne im Käfigboden wird als Surrogat für einen im Freileben vorkommenden zielgerichteten Nahrungstransport angesehen und im schließlichen Versenken des überstehenden Schnabelteils in der Rinne zum Fassen der Nahrung wird das normale Nahrungsstochern der Art erblickt. — Es wird eine Hypothese zur mutmaßlichen Entstehung der verblüffenden Umorientierung entwickelt.

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Summary A short note byFlint about the feeding habits of an Oystercatcher(Haematopus ostralegus) in captivity with only three quarters of his under bill gave reason for reflections which of the innate motor patterns of the species might have helped the bird in finding its new method. — At first a morsel of food in the tray is stabbed with the upper bill. This is compared with the stabbing of mussels and crabs. The morsel is then flung out of the tray in the way of getting rid of annoying matter. After this the bit is pushed along the floor towards a slit and right across it. This remarkable performance seems to be a substitute for an oriented food transport directed to a special place occurring under full scope conditions. The sinking of the beak into the cleft in order to seize the food at last may be identical with the usual probing for worms. — A conjecture is given as to how this bewildering reorganization of feeding habits might have come into being.

     

Dextran sulfate-dependent fusion of liposomes containing cationic stearylamine.

The incorporation of the positively charged stearylamine into phosphatidylcholine liposomes was studied by measuring electrophoretic mobilities. Up to a molar ratio SA/PC = 0.5 an increase of the positive zeta potential can be observed. Addition of the negatively charged macromolecule dextran sulfate leads to a change of the sign of the surface potential of the PC/SA liposomes indicating binding of the macromolecule to the surface. This process is accompanied by an increase in turbidity, which is dependent on the molecular weight of the dextran sulfate and the SA concentration (measured by turbidimetry). Using the NBD/Rh and Pyr-PC fluorescence assays the fusion of SA containing liposomes was investigated. A strong influence of the SA content and molecular weight of dextran sulfate on the fusion extent was observed. The fusion extent is proportional to the SA content in the PC membrane and the molecular weight of dextran sulfate. PC/SA/PE liposomes exhibit a higher fusion extent after addition of dextran sulfate compared to PC/SA liposomes indicating that PE additionally destabilizes the bilayer. Freeze-fracture electron microscopy reveals that the reaction products are large complexes composed of multilamellar stacks of tightly packed, straight membranes and aggregated vesicles. The tight packing of the membranes in the stacks (and the narrow contact of the aggregated vesicles) indicates a strong adherence of opposite membrane surfaces induced by dextran sulfate.