Comparing the Lipid Membrane Affinity and Permeation of Drug-like Acids: The Intriguing Effects of Cholesterol and Charged Lipids

Purpose: Lipid bilayers regulate the passage of solutes into and between cellular compartments. A general prerequisite for this passage is the partitioning of the solute into the bilayer. We investigated the relationship between bilayer partitioning and permeation of three drug-like acids in liposomal systems consisting of phosphatidylcholine alone or mixed with cholesterol or charged lipids. Materials and Methods: Bilayer partitioning was determined by equilibrium dialysis. Bilayer permeation was studied with a luminescence assay which is based on the energy transfer of the permeant to intraliposomal terbium(III). Results: The influence of the lipid composition on the pH-dependent membrane affinity was in accordance with the membrane rigidity and possible electrostatic interactions between the acids and the lipids. However, there was no direct relationship between membrane affinity and permeation. This seeming discrepancy was closer analyzed with numerical simulations of the permeation process based on the single rate constants for partitioning and translocation. The simulations were in line with our experimental findings. Conclusions: Depending on the single rate constants and on the geometry of the system, lipid bilayer permeation may positively, negatively or not correlate with the bilayer affinity of the permean

Evaluation of a newly developed flipped-classroom course on interprofessional practice in health care for medical students

Interprofessional education is expected to promote collaborative practice and should therefore be included in health professionals’ curricula. Reports on interprofessional curricular development and its evaluation are rare. We therefore undertook a comprehensive quantitative and qualitative evaluation of a new, mandatory course on interprofessional collaboration for medical students during their third year of the Bachelor of Medicine study programme. The newly developed and implemented course spans over six weeks and was designed in a hybrid, flipped-classroom format. It incorporates experience- and case-based learning as well as interactions with other health professionals. Each student completes an eLearning and a clinical workshadowing individually before attending the – due to the pandemic – virtual live lectures. To assess quality and usefulness of teaching-learning formats and course structure to learn about interprofessional collaboration and to develop interprofessional competencies and identity, a quantitative and qualitative evaluation was performed with more than 280 medical students and 26 nurse educators from teaching hospitals using online surveys (open & closed-ended format). Data were analyzed descriptively and using content analysis processes. Students appreciated the flipped-classroom concept, the real-world case-based learning scenarios with interprofessional lecturer teams, and the possibility of an experience-based learning opportunity in the clinical setting including interaction with students and professionals from other health professions. Interprofessional identity did not change during the course. Evaluation data showed that the course is a promising approach for teaching-learning interprofessional competencies to medical students. The evaluation revealed three factors that determined the success of this course, namely, a flipped-classroom concept, the individual workshadowing of medical students with another health professional, mainly nurses, and live sessions with interprofessional teaching-learning teams. The course structure and teaching-learning methods showed potential and could serve as a template for interprofessional course development in other institutions and on other course topics

Training oncology physicians to advise their patients on complementary and integrative medicine: An implementation study for a manual‐guided consultation

Background: The unmonitored use of complementary medicine in patients with cancer can be associated with an increased risk of safety-related issues, such as lower adherence to conventional cancer therapies. Training oncology physicians to advise their patients about the effectiveness and safety of these therapies could improve this situation. Methods: The objective of this study was to develop and pretest a consultation framework that has high potential to be widely implemented. The framework comprises: 1) a systematically developed and tested, manualized, guided consultation; and 2) blended learning training (e-learning and communication skills training workshop) to upskill oncology physicians in advising their patients on complementary and integrative medicine (CIM). For this implementation study, mixed methods were used to develop the manual (literature review, consensus procedure, pilot testing) and the training (questionnaires and interviews with oncology physicians and patients with cancer and an examination of the skills in a setting with standardized patients). Results: The training was tested with 47 oncology physicians from across Germany. The manual-guided consultation (context: general information on the setting and communication techniques; inform: consultation duration and content; capture: previous CIM use; prioritize: focus on consultation; advise: evidence-based CIM recommendations; discuss, advise, accept, or advise against other CIM; concretize advice: summary and implementation; and monitor: documentation) was considered suitable. The structure and time frame (maximum, 20 minutes) of the consultation as well as the training were feasible and well accepted. Conclusions: The current study demonstrates that the KOKON-KTO framework (a German acronym for Competence Network for Complementary Medicine - Consultation Training for Oncology Physicians) is suitable for training oncology physicians. Its implementation can lead to better physician-patient communication about CIM in cancer

Training oncology physicians to advise their patients on complementary and integrative medicine: An implementation study for a manual‐guided consultation

BACKGROUND: The unmonitored use of complementary medicine in patients with cancer can be associated with an increased risk of safety-related issues, such as lower adherence to conventional cancer therapies. Training oncology physicians to advise their patients about the effectiveness and safety of these therapies could improve this situation. METHODS: The objective of this study was to develop and pretest a consultation framework that has high potential to be widely implemented. The framework comprises: 1) a systematically developed and tested, manualized, guided consultation; and 2) blended learning training (e-learning and communication skills training workshop) to upskill oncology physicians in advising their patients on complementary and integrative medicine (CIM). For this implementation study, mixed methods were used to develop the manual (literature review, consensus procedure, pilot testing) and the training (questionnaires and interviews with oncology physicians and patients with cancer and an examination of the skills in a setting with standardized patients). RESULTS: The training was tested with 47 oncology physicians from across Germany. The manual-guided consultation (context: general information on the setting and communication techniques; inform: consultation duration and content; capture: previous CIM use; prioritize: focus on consultation; advise: evidence-based CIM recommendations; discuss, advise, accept, or advise against other CIM; concretize advice: summary and implementation; and monitor: documentation) was considered suitable. The structure and time frame (maximum, 20 minutes) of the consultation as well as the training were feasible and well accepted. CONCLUSIONS: The current study demonstrates that the KOKON-KTO framework (a German acronym for Competence Network for Complementary Medicine - Consultation Training for Oncology Physicians) is suitable for training oncology physicians. Its implementation can lead to better physician-patient communication about CIM in cancer

Comparison of permeation through phosphatidylcholine bilayers of N-Dipicolinyl-alpha- and -beta-Oligopeptides

Published in Chemistry & Biodiversity, 2006; 3 (11):1181-1201 at www.interscience.wiley.comCell-membrane permeation of small therapeutic peptides and peptidomimetics is a fundamental issue in pharmaceutical research. Using a Tb³⁺-based permeation assay, we have examined the ability of α- and β-peptides, bearing proteinogenic side chains and an N-terminal dipicolinic acid (DPA) monoamide group, to enter liposomes composed of egg phosphatidylcholine bilayers. A series of 12 DPA–peptides of increasing chain length was prepared and characterized by CD and NMR analysis. An interesting destabilizing effect of the N-terminal DPA group on the helical structure of a β-hexapeptide was discovered. Significant differences in permeation were observed between the DPA-α- and the DPA-β-peptides, with all β-peptidic compounds permeating better than their α-analogs. Thus, β-peptides have been shown to interact with lipid bilayers in a manner that is distinctly different from that of α-peptides. Together with the fact that β-peptides are proteolytically stable in mammalian organisms, and that they fold to form helices and hairpin turns with short chain lengths, the new results further emphasize the biomedical potential of β-peptides.James Gardiner, Anita V. Thomae, Raveendra I. Mathad, Dieter Seebach and Stefanie D. Kräme

Comparing the lipid membrane affinity and permeation of drug-like acids: The intriguing effects of cholesterol and charged lipids

ISSN:0724-8741ISSN:1573-904

Development, Implementation, and Evaluation of an e-Learning in Integrative Oncology for Physicians and Students Involving Experts and Learners: Experiences and Recommendations

In this project, an e-Learning program for complementary and integrative medicine in oncology was systematically developed, implemented, and evaluated in a stepwise procedure. Learning objectives and content were defined within the KOKON project network, considering the educational competencies for integrative oncology. To design a valuable e-Learning, experts were involved in all relevant steps of the process, as well as stakeholders from various target groups (undergraduates: medicine students, postgraduates: oncology physicians). We used mixed methods including quantitative surveys, progress tests, and qualitative focus groups. The developed e-Learning program led to a significant measurable knowledge gain about complementary and integrative medicine. In parallel, physicians and students were subjectively satisfied with the training. For the majority of e-Learning elements, the needs of both target groups are comparable. Furthermore, both groups emphasized the value of formative assessment tools for gaining knowledge. From the various surveys and experiences collected in this project, we derive recommendations for others developing e-Learning programs

Exploring Barrier Mechanisms Relevant for Drug Therapy

Membranes play an important role in the compartmentalization of cells and organs. Up to 500 different lipids have been reported to be present in different biological membranes. The origin and meaning of this diversity is not well understood. Membranes mediate the necessary separation between organizational units, but also provide the possibility to connect them. Overcoming the membrane barriers within the body is a major task for any therapeutic agent. The research of the Wunderli group is concentrated on elucidating the basis of drug–membrane interaction and permeation processes, on unraveling the mechanism of action of multi-substrate membrane transporters such as the multi-drug resistance protein P-glycoprotein (P-gp), and on the modulation of paracellular diffusion. Three major projects are pursued: (1) drug–membrane interaction and permeation studies with liposomes of different lipid composition; (2) studies on the mechanism of action of the P-gp with proteoliposomes; (3) modulation of the tight junctions (TJs) of cell barriers to enhance the paracellular transport of hydrophilic therapeutic entities, e.g. peptides

Permeation of a beta-heptapeptide derivative across phospholipid bilayers

Copyright © 2007 Elsevier B.V. All rights reserved.Toshinori Shimanouchi, Peter Walde, James Gardiner, Yogesh R. Mahajan, Dieter Seebach, Anita Thomae, Stefanie D. Krämer, Matthias Voser and Ryoichi Kuboihttp://www.elsevier.com/wps/find/journaldescription.cws_home/601272/description#descriptio