By means of the scanning differential calorimetry, x-ray diffractometry, and the dynamic light scattering, we have systematically studied the phase and packing properties of dipalmitoylphosphatidylcholine vesicles or multibilayers in the presence of ethanol. We have also determined the partial ternary phase diagram of such dipalmitoylphosphatidylcholine/water/ethanol mixtures. The directly measured variability of the structural bilayer parameters implies that ethanol binding to the phospholipid bilayers increases the lateral as well as the transverse repulsion between the lipid molecules. This enlarges the hydrocarbon tilt (by up to 23 degrees) and molecular area (by < or = 40%). Ethanol-phospholid association also broadens the interface and, thus, promotes lipid headgroup solvation. This results in excessive swelling (by 130%) of the phosphatidylcholine bilayers in aqueous ethanol solutions. Lateral bilayer expansion, moreover, provokes a successive interdigitation of the hydrocarbon chains in the systems with bulk ethanol concentrations of 0.4-1.2 M. The hydrocarbon packing density as well as the propensity for the formation of lamellar gel phases simultaneously increase. The pretransition temperature of phosphatidylcholine bilayers is more sensitive to the addition of alcohol (initial shift: delta Tp = 22 degrees C/mol) than the subtransition temperature (delta Ts reversible 5 degrees C/mol), whereas the chain-melting phase transition temperature is even less affected (delta Tm = 1.8 degrees C/mol). After an initial decrease of 3 degrees for the bulk ethanol concentrations below 1.2 M, the Tm value increases by 2.5 degrees above this limiting concentration. The gel-phase phosphatidylcholine membranes below Tm are fully interdigitated above this limiting concentration. The chain tilt on the fringe of full chain interdigitation is zero and increases with higher ethanol concentrations. Above Tm, some of the lipid molecules are solubilized by the bound ethanol molecules. More highly concentrated ethanol solutions (> 7 M) solubilize the phosphatidylcholine bilayers with fluid chains fully and result in the formation of mixed lipid-alcohol micelles.

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COMMUNrCATlONS P/ii..\. 1973. 2. 41; G. te Velde. E. J. Baerends, J. Compuf. P h w . 1992. 99, 84. Computational details: A local spin density approximation (S. H. Vosko, L. Wilk. M. h'usair, Cun. J Phw. 1980,58, 1200) was used in connection with the self-interaction correction ofStoll et al. (H. Stoll, C. M. E. Pavlidou, H. Preuss, 7/1ror. C / I I~. A r f u 1978.49, 143) and a gradient correction to the exchange part of the potcntial (A D. Becke, Phys. Rev A 1988, 38, 3098). Frozen core approximntion with the following Slater-type-orbital (STO) basis sets for the valence shell$. V. double.< for 3s. 3p. and 4s and triple-< for 3d, 0, N. and C, double.; for 7s and 2p: H double.; for Is. A set of auxiliary s. p, d, f. and g type STOa centered on the different atoms was used to fit the electronic density [15] a ) L. Noodleman.

PurposeComparison of the dissociation kinetics of rapid-acting insulins lispro, aspart, glulisine and human insulin under physiologically relevant conditions.MethodsDissociation kinetics after dilution were monitored directly in terms of the average molecular mass using combined static and dynamic light scattering. Changes in tertiary structure were detected by near-UV circular dichroism.ResultsGlulisine forms compact hexamers in formulation even in the absence of Zn2+. Upon severe dilution, these rapidly dissociate into monomers in less than 10 s. In contrast, in formulations of lispro and aspart, the presence of Zn2+ and phenolic compounds is essential for formation of compact R6 hexamers. These slowly dissociate in times ranging from seconds to one hour depending on the concentration of phenolic additives. The disadvantage of the long dissociation times of lispro and aspart can be diminished by a rapid depletion of the concentration of phenolic additives independent of the insulin dilution. This is especially important in conditions similar to those after subcutaneous injection, where only minor dilution of the insulins occurs.ConclusionKnowledge of the diverging dissociation mechanisms of lispro and aspart compared to glulisine will be helpful for optimizing formulation conditions of rapid-acting insulins.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-017-2233-0) contains supplementary material, which is available to authorized users.

SummaryBackground: Patients with neuroischemic diabetic foot syndrome (DFS) may need arterial revascularization, minor amputations, débridements as well as meticulous wound care. Unfortunately, postoperative outpatient care is frequently inadequate. Th is is especially true for Germany, where the in-and outpatient sectors are funded and managed separately, with poor communication between the two. Th us, many patients may be readmitted to the hospital following successful treatment and discharge. In an attempt to overcome these problems, we looked at whether an integrated case management (CM) system for outpatient care according to in-hospital standards might improve patients care and avoid readmissions. In addition we analyzed the length of hospital stay (LOS) as well as hospital costs. Patients and methods: In this retrospective cohort study patients with DFS, bypass surgery and foot surgery aft er implementation of the CM (study group; n = 376) were compared with a matched historic control group (HCG; n = 190) including the fl at rate revenues (G-DRG K01B). Following a standardized assessment, integrated trans-sectoral CM care was off ered to 116 patients (CMP). Results: Th e proportion of patients who were readmitted to hospital was reduced in CMP compared to HCG (8.8 vs. 16.4 %; p < 0.01), with consequent reduction of case consolidations (9.7 % versus 17.8 %, p < 0.001). Although initially, the mean LOS was higher in the CMP patients, the reduction in readmissions meant that this integrated CM program improved the hospital's economic situation. Conclusions: A hospital-based integrated CM system signifi cantly reduces the hospital readmissions in patients with neuroischemic DFS following bypass surgery, with lower hospital costs.