Self-Assembly of Supramolecular Triblock Copolymer Complexes

Four different poly(tert-butoxystyrene)-b-polystyrene-b-poly(4-vinylpyridine) (PtBOS-b-PS-b-P4VP) linear triblock copolymers, with the P4VP weight fraction varying from 0.08 to 0.39, were synthesized via sequential anionic polymerization. The values of the unknown interaction parameters between styrene and tert-butoxystyrene and between tert-butoxystyrene and 4-vinylpyridine were determined from random copolymer blend miscibility studies and found to satisfy 0.031<χS,tBOS<0.034 and 0.39<χ4VP,tBOS<0.43, the latter being slightly larger than the known 0.30<χS,4VP≤0.35 value range. All triblock copolymers synthesized adopted a P4VP/PS core/shell cylindrical self-assembled morphology. From these four triblock copolymers supramolecular complexes were prepared by hydrogen bonding a stoichiometric amount of pentadecylphenol (PDP) to the P4VP blocks. Three of these complexes formed a triple lamellar ordered state with additional short length scale ordering inside the P4VP(PDP) layers. The self-assembled state of the supramolecular complex based on the triblock copolymer with the largest fraction of P4VP consisted of alternating layers of PtBOS and P4VP(PDP) layers with PS cylinders inside the latter layers. The difference in morphology between the triblock copolymers and the supramolecular complexes is due to two effects: (i) a change in effective composition and, (ii) a reduction in interfacial tension between the PS and P4VP containing domains. The small angle X-ray scattering patterns of the supramolecules systems are very temperature sensitive. A striking feature is the disappearance of the first order scattering peak of the triple lamellar state in certain temperature intervals, while the higher order peaks (including the third order) remain. This is argued to be due to the thermal sensitivity of the hydrogen bonding and thus directly related to the very nature of these systems.

Phase II trial of sagopilone, a novel epothilone analog in metastatic melanoma

BackgroundSagopilone is a novel fully synthetic epothilone with promising preclinical activity and a favourable toxicity profile in phase I testing.MethodsA phase II pharmacokinetic and efficacy trial was conducted in patients with metastatic melanoma. Patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate haematological, and organ function, with up to 2 previous chemotherapy and any previous immunotherapy regimens. Sagopilone, 16 mg m⁻², was administered intravenously over 3 h every 21 days until progression or unacceptable toxicity.ResultsThirty-five patients were treated. Sagopilone showed multi-exponential kinetics with a mean terminal half-life of 64 h and a volume of distribution of 4361 l m⁻² indicating extensive tissue/tubulin binding. Only grade 2 or lower toxicity was observed: these included sensory neuropathy (66%), leukopenia (46%), fatigue (34%), and neutropenia (31%). The objective response rate was 11.4% (one confirmed complete response, two confirmed partial responses, and one unconfirmed partial response). Stable disease for at least 12 weeks was seen in an additional eight patients (clinical benefit rate 36.4%).ConclusionSagopilone was well tolerated with mild haematological toxicity and sensory neuropathy. Unlike other epothilones, it shows activity against melanoma even in pretreated patients. Further clinical testing is warranted

The Peculiarities of Clinico-Paraclinical Data in Children with Diagnosis of “Subfebrility of Unidentified Genesis”

The results of study of 36 children’s clinical histories with referral diagnosis of “long-lasting subfebrility of unidentified genesis” are given in this article. Subfebrility occurs more often in mid-childhood children, who belong to the group of frequently ill children and it is characterized by monothermia in 82.4% of cases. The main subjective sign of a subfebrile condition is “chronic fatigue” syndrome. Laboratory features of subfebrile syndrome are: anemia of the 1st degree, neutrophylia due to the segment-nuclear forms, moderate monocytopenia, and slight increase of ESR. In 94.5% of cases the changes for herpetic infection using ELISA test were detected, that indicated previous infection or virus persistence of varying degree of activity and was argued by the increase of general serum IgG level. The key reasons of the fever of uncertain origin became: in 72.99% of cases – bacterial polytopic infections (in general infections of a biliary system), in 18.9% of cases – active  persistent herpetic infections with lymphadenopathy, in 8.11% of cases – vegetative dysfunction. Analysis of procalcitonine level in patients with fever of unknown origin indicates, that it can be used as a marker of clinical visible bacterial infection and can confirm non-viral genesis of the probable disease. Long-lasting subfebrile conditions have no self-meaning and are related to latent foci of infection, persistent virusemia with lymphadenopathy signs

Use of the upside-down method to prepare porous polymer films with tunable surface pore sizes

10.1021/la8035264Langmuir25151-54LANG