Organogels from trehalose difatty ester amphiphiles.

Saccharide diesters have been recently shown to be excellent gelators of vegetable oils. In this paper, different fatty acid trehalose diesters were synthesized by a selective enzymatic transesterification performed only on the primary hydroxyl group of the trehalose. The resulting trehalose diesters demonstrated their ability to self-assemble in a large variety of edible vegetable oils with a minimum gelation concentration of 0.25 wt%/v. Microscopic analysis and X-ray scattering studies indicate that the gels are obtained by the self-assembly of trehalose diesters in crystalline fibers constituting the tridimensional network. The rheological study revealed that the properties of the gels depend on the kind of fatty acid grafted on the trehalose but are also influenced by the vegetable oil composition.

The combination of block copolymers and phospholipids to form giant hybrid unilamellar vesicles (GHUVs) does not systematically lead to "intermediate" membrane properties.

In this work, the elasticity under stretching as well as the fluidity of Giant Hybrid Unilamellar Vesicles (GHUV) has been studied. The membrane structuration of these GHUVs has already been studied at the micro and nanoscale in a previous study of the team. These GHUVs were obtained by the association of a fluid phospholipid (POPC) and a triblock copolymer, poly(ethyleneoxide)-b-poly(dimethylsiloxane)-b-poly(ethyleneoxide). Although the architecture of triblock copolymers can facilitate vesicle formation, they have been scarcely used to generate GHUVs. We show, through micropipette aspiration and FRAP experiments, that the incorporation of a low amount of lipids in the polymer membrane leads to a significant loss of the toughness of the vesicle and subtle modification of the lateral diffusion of polymer chains. We discuss the results within the framework of the conformation of the triblock copolymer chain in the membrane and in the presence of lipid nanodomains.

Mixing Block Copolymers with Phospholipids at the Nanoscale: From Hybrid Polymer/Lipid Wormlike Micelles to Vesicles Presenting Lipid Nanodomains.

Hybrids, i.e., intimately mixed polymer/phospholipid vesicles, can potentially marry in a single membrane the best characteristics of the two separate components. The ability of amphiphilic copolymers and phospholipids to self-assemble into hybrid membranes has been studied until now on the submicrometer scale using optical microscopy on giant hybrid unilamellar vesicles (GHUVs), but limited information is available on large hybrid unilamellar vesicles (LHUVs). In this work, copolymers based on poly(dimethylsiloxane) and poly(ethylene oxide) with different molar masses and architectures (graft, triblock) were associated with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Classical protocols of LUV formation were used to obtain nanosized self-assembled structures. Using small-angle neutron scattering (SANS), time-resolved Förster resonance energy transfer (TR-FRET), and cryo-transmission electron microscopy (cryo-TEM), we show that copolymer architecture and molar mass have direct influences on the formation of hybrid nanostructures that can range from wormlike hybrid micelles to hybrid vesicles presenting small lipid nanodomains.

Detection of pyrrolizidine alkaloids in German licensed herbal medicinal teas.

BACKGROUND: Because of the hepatotoxic, mutagenic, and cancerogenic effects of pyrrolizidine alkaloids (PAs) the German Federal Institute for Risk Assessment (BfR) recommends not to exceed a daily PA intake of 0.007 µg/kg body weight (0.42 µg/60 kg adult). In a recent study conducted by the BfR, up to 5647 µg PA/kg dried herbal material were detected in tea products marketed as food. PURPOSE: The present study aimed at elucidating whether medicinal teas licensed or registered as medicinal products contain PAs as well. STUDY DESIGN: One hundred sixty-nine different commercially available medicinal teas, i.e. 19 nettle (Urtica dioica L.), 12 fennel (Foeniculum vulgare Mill.), 14 chamomile (Matricaria recutita L.), 11 melissa (Melissa officinalis L.) and 4 peppermint (Mentha piperita L.) teas as well as 109 tea mixtures were analyzed for the presence of 23 commercially available PAs. METHOD: LC/MS was used for the determination of the PAs RESULTS: In general, the total PA contents ranging 0-5668 µg/kg. Thirty percent of the tested single-ingredient tea products and 56.9% of the tested medicinal tea mixtures were found to contain PA concentrations above the limit of quantification (LOQ) of 10 µg/kg. In 11 medicinal teas PA contents >300 µg/kg dry herb were determined thus exceeding the recommended limit for PA intake by BfR. In addition three products of the investigated tea mixtures revealed extremely high PA contents of 4227, 5137, and 5668 µg/kg. Generally, single-ingredient tea products contained much less or even no detectable amounts of PAs when compared to the tea mixtures. PAs in the range between 13 and 1080 µg/kg were also detected in five analyzed aqueous herbal infusions of the medicinal tea mixture products with the highest PA content. Two out of the five investigated herbal infusions exceeded the recommended BfR limit for PA intake. CONCLUSION: This study demonstrates clearly that also medicinal teas licensed as medicinal products may partly contain high amounts of PAs exceeding current recommendations. For that reason manufacturers are advised to carry out more rigorous quality control tests devoted to the detection of PAs. This is very important to minimize PAs in medicinal teas accounting for possible additional exposure of the consumer to PAs from other food sources (e.g. honey).

Phase Separation and Nanodomain Formation in Hybrid Polymer/Lipid Vesicles.

Hybrid polymer/lipid large unilamellar vesicles (LUVs) were studied by small angle neutron scattering (SANS), time-resolved Förster resonance energy transfer (TR-FRET), and cryo-transmission electron microscopy (cryo-TEM). For the first time in hybrid vesicles, evidence for phase separation at the nanoscale was obtained, leading to the formation of stable nanodomains enriched either in lipid or polymer. This stability was allowed by using vesicle-forming copolymer with a membrane thickness close to the lipid bilayer thickness, thereby minimizing the hydrophobic mismatch at the domain periphery. Hybrid giant unilamellar vesicles (GUVs) with the same composition have been previously shown to be unstable and susceptible to fission, suggesting a role of curvature in the stabilization of nanodomains in these structures.

Recent trends in the tuning of polymersomes' membrane properties.

"Polymersomes" are vesicular structures made from the self-assembly of block copolymers. Such structures present outstanding interest for different applications such as micro- or nano-reactor, drug release or can simply be used as tool for understanding basic biological mechanisms. The use of polymersomes in such applications is strongly related to the way their membrane properties are controlled and tuned either by a precise molecular design of the constituting block or by addition of specific components inside the membrane (formulation approaches). Typical membrane properties of polymersomes obtained from the self-assembly of "coil coil" block copolymer since the end of the nineties will be first briefly reviewed and compared to those of their lipidic analogues, named liposomes. Therefore the different approaches able to modulate their permeability, mechanical properties or ability to release loaded drugs, using macromolecular engineering or formulations, are detailed. To conclude, the most recent advances to modulate the polymersomes' properties and systems that appear very promising especially for biomedical application or for the development of complex and bio-mimetic structures are presented.

Biomimetic doxorubicin loaded polymersomes from hyaluronan-block-poly(gamma-benzyl glutamate) copolymers.

Using "click chemistry" as an easy and versatile synthetic strategy to combine hyaluronan and polyglutamate blocks, we have prepared nanovesicles (polymersomes) that present a controlled size, excellent colloidal stability, and a high loading capacity for hydrophilic and hydrophobic drugs. The unique feature of our concept is the use of hyaluronan, a polysaccharide with known capacity for targeting cancer-related protein receptors, as the hydrophilic portion of a block copolymer system. The cytotoxicity and internalization mechanism of doxorubicin-loaded polymersomes have been evaluated in C6 glioma tumor cell lines. The dual purpose served by hyaluronan, as both a hydrophilic block critical to vesicle formation and a binding agent for biological targets, breaks new ground in terms of multifunctional nanomaterial design for drug delivery.

Role of block copolymer nanoconstructs in cancer therapy.

Drug, gene, and protein delivery is a very challenging and exciting area in nanobiotechnology where block copolymers are increasingly considered especially as carriers for pharmacotherapy of various cancers. Cancer chemotherapy is particularly challenging because of nonselective distribution of drugs, associated severe toxicity, multidrug resistance, and chronic treatments influencing the quality-adjusted life of patients. These limitations lead to incomplete cure and render many drugs ineffective in treating cancers. Liposomes are currently more advanced in clinical trials and industrial developments but they lack stability and pose difficulties in functionalizing liposomes. More recently, various types of polymer-based nanoconstructs have been designed and synthesized, and are being investigated for the cancer chemotherapy applications. This review discusses the most significant and recent developments on specific self-assembled block copolymers as a carrier system such as micelles and vesicles, which can be successfully used to enhance the solubility of hydrophobic drugs, helpful in targeting selective sites in the body, delivering active molecules in a control manner, and reducing the side effects in the treatment of cancer.

Dermal absorption of permethrin following topical administration.

OBJECTIVE: Permethrin is an insecticide used in the treatment of lice and scabies infections. Although its efficacy and safety have been well documented, pharmacokinetic data are sparse. The objective of this study was to determine the systemic exposure of permethrin and the duration of residence in the human body following topical administration. METHODS: The study consisted of three parts. In six young healthy men (part 1), 50 ml of an ethanolic solution containing 215 mg permethrin (cis/trans: 25/75) was administered to the hair of the head. In another six young healthy men (part 2) and in six male or female scabies patients (part 3), 60 g of cream containing 3 g permethrin was administered to the skin of the whole body. Urine was collected up to 168 h post-dose. Urinary excretion of the main metabolite of permethrin, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, and its conjugates was measured using a gas chromatography/electron capture detection method. RESULTS: Pharmacokinetics were similar in all study parts. The time of maximal urinary excretion rate was 12.3, 20.0 and 14.6 h, terminal elimination half-life was 32.7, 28.8 and 37.8 h and urinary recovery of the metabolite reached 0.35, 0.47 and 0.52 M percent of the permethrin dose, respectively, in parts 1, 2 and 3 (means). The treatment was well tolerated. CONCLUSIONS: The extent of systemic exposure following external therapeutic administration of permethrin is very low compared with doses used for preclinical toxicity studies, and elimination is virtually complete after 1 week. These data provide the pharmacokinetic basis for the clinical safety of topical permethrin.

Attenuation of sepsis-related immunoparalysis by continuous veno-venous hemofiltration in experimental porcine pancreatitis.

OBJECTIVES: In light of evidence suggesting that hemofiltration favorably influences septic diseases by removing sepsis mediators, the impact of different modalities of continuous veno-venous hemofiltration (CVVH) on outcome and immunologic derangements in porcine pancreatogenic sepsis was evaluated. DESIGN: Randomized, controlled intervention trial. SUBJECTS: Forty-eight minipigs of either sex. INTERVENTIONS: Pancreatitis was induced by intraductal injection of sodium taurocholate (4%, 1 mL/kg body weight [BW]) and enterokinase (2 U/kg BW). Animals were allocated either to untreated controls-group 1-or to one of three treatment groups-group 2: low-volume CVVH (20 mL/kg BW), no change of hemofilters; group 3: low-volume CVVH, filters changed every 12 hrs; and group 4: high-volume CVVH (100 mL/kg BW), filters changed every 12 hrs. Survival represented the major parameter of the study. Serum cytokine levels, sepsis-related down-regulation of major histocompatibility complex II and CD14 expression on leukocytes, bacterial translocation, and endotoxemia were further parameters evaluated in the study. MEASUREMENTS AND MAIN RESULTS: High-volume CVVH combined with periodic filter change was significantly superior compared with less intensive treatment modalities (low-volume CVVH, no filter change) in sepsis protection. Long-term survival (>60 hrs) was found in 67% of group 4 and 33% of group 3 animals (p <.05), whereas in controls and group 2 no animal survived. CVVH ameliorated the initial serum tumor necrosis factor-alpha response and prevented sepsis-induced in vitro endotoxin hyporesponsiveness. Down-regulation of major histocompatibility complex II and CD14 expression on monocytes was significantly improved by CVVH. Improved oxidative burst and phagocytosis capacity in polymorphonuclear leukocytes suggested that leukocyte function was stabilized by CVVH. Also, CVVH significantly reduced bacterial translocation and endotoxemia. CONCLUSIONS: Hemofiltration reversed sepsis-induced immunoparalysis in a porcine model of bile acid-induced pancreatitis. Implications for human pancreatitis must be validated in prospective, clinical protocols.

Validated high-performance liquid chromatographic assay for the determination of promazine in human plasma. Application to pharmacokinetic studies.

A high-performance liquid chromatographic method for the determination of promazine in human plasma is described. The assay involves a single-step liquid-liquid extraction using pentane-2-propanol (98:2, v/v). The analyte of interest and the internal standard chlorpromazine were separated on a Spherisorb CN column using a mobile phase of acetonitrile-50 mM ammonium acetate (9:1, v/v). Electrochemical detection was achieved using an applied potential of +750 mV. The assay was validated according to international requirements prior to application to a pharmacokinetic study and was found to be specific, accurate and precise with a linear range of 0.25-25 ng ml(-1).

[Development of an HPLC method for determination of chloroquine in plasma]. / Entwicklung einer HPLC-Methode zur Bestimmung von Chloroquin in plasma.

A simple, rapid and sensitive ion-pair high-performance liquid chromatographic method is described, which allows the quantification of chloroquine in human plasma. 7-Chloro-4-(4-ethylpropylamino-1-methyl-butylamino)quinoline was synthesized and used as internal standard. After extraction by toluene from 1 ml plasma, chloroquine was reextracted with 15% phosphoric acid from the organic phase. Chromatographic separation on a RP-18 column and UV-detection (343 nm) allows sensitive determination of chloroquine in plasma with a lower limit of quantification of 2.5 ng/ml. The method was successfully applied to human plasma samples from 16 subjects after oral administration of 250 mg chloroquine diphosphate.

Developing a Reliable Testing Protocol for the Hydra-Fitness Upper Body OmniTron.

Evaluation of the reliability of musculoskeletal testing equipment is an important step in establishing the usefulness of an assessment device's data. The purposes of this study were to determine the reliability of a specific upper body OmniTron testing protocol and to estimate reliabilities for several other protocols in order to determine the optimal one. After upper body warm-up, 32 subjects (22 men, 10 women; mean age = 20.7 +/- 2.6 years) were tested on the Hydra-Fitness OmniTron chest press (CP) and upper back pull (BP) exercise at a slow speed and high resistance. Peak force, work, and power values were obtained for each subject during a protocol consisting of two test sessions of four repetitions each, with an intervening 5-minute rest period. The first repetition of each test session was considered a warm-up, and data from these were discarded. A repeated measures ANOVA was conducted on the main effects (tests and repetitions), and a generalizability analysis was performed. Mean peak force output values were significantly higher (p < .0001) during the second test session (Test 1 CP = 654.9 +/- 167.5 N, Test 2 CP = 690.0 +/- 179.1 N; Test 1 BP = 547.5 +/- 139.0 N, Test 2 BP = 568.2 +/- 153.9 N), possibly indicating the presence of a learning effect. Work and power data showed similar trends, as peak force, work, and power were highly correlated with one another (r >/= .90). Reliability of the protocol was estimated for the peak force data of CP and BP. The coefficients were .993 and .985, respectively. Generalizability forecasting for alternate protocols demonstrated that for both CP and BP, a minimum of two tests of at least three repetitions each were necessary for optimum reliability, although all evaluated combinations exhibited high reliability (r >/= .949). This study suggests that the two test session/three repetition protocol (four repetitions, including the initial discarded one) with a 5-minute rest is highly reliable and may be desirable for use with subjects being tested for the first time in order to counteract a possible learning effect. The clinician may also choose another protocol shown to be reliable by this investigation. J Orthop Sports Phys Ther 1992;16(2):87-91.

Use of the air-inflated jacket in football.

Injuries to the rib cage are common in football, but little has been done to protect this area. This paper discusses the effectiveness and usefulness of a protective jacket in football. The jacket is highly durable, constructed of urethane-coated nylon, and heat-sealed to take on the shape of several cylinders interconnected by fabric valves which constrict in response to a sudden blow. Its exterior is covered by a 1/8-inch thick Lexan (General Electric, Toledo, OH) shield. The jacket weighs 6.5 oz. It showed impressive results when tested. Testing was done by forcefully swinging a baseball bat against the rib cage protected by the jacket. By digitization of high speed movie filming at 500 frames/second, we were able to determine the speed, velocity, and area of contact. The amount of force deflection was calculated to be 587.6 psi. To inflict this force, a player would have to be traveling 60 miles/hour and strike his opponent with the heel. This lightweight, air-inflated, padded jacket has protected and prevented rib cage injuries in professional athletes. It is accepted well by players. This suggests that similar protective equipment for other areas would be useful and represents an advancement in preventing injury.