Coupling AFM,DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study

Polymeric film-forming systems have emerged as an esthetically acceptable option for targeted, less frequent and controlled dermal drug delivery. However, their dynamic nature (rapid evaporation of solvents leading to the formation of thin films) presents a true characterization challenge. In this study, we tested a tiered characterization approach, leading to more efficient definition of the quality target product profiles of film-forming systems. After assessing a number of physico-chemico-mechanical properties, thermal, spectroscopic and microscopic techniques were introduced. Final confirmation of betamethasone dipropionate-loaded FFS biopharmaceutical properties was sought via an in vitro skin permeation study. A number of applied characterization methods showed complementarity. The sample based on a combination of hydrophobic Eudragit^® RS PO and hydroxypropyl cellulose showed higher viscosity (47.17 ± 3.06 mPa·s) and film thickness, resulting in sustained skin permeation (permeation rate of 0.348 ± 0.157 ng/cm² h), and even the pH of the sample with Eudragit^® NE 30D, along with higher surface roughness and thermal analysis, implied its immediate delivery through the epidermal membrane. Therefore, this study revealed the utility of several methods able to refine the number of needed tests within the final product profile.     

Signaturen durch elektronische Agenten

Elektronische Agenten können auf sämtlichen Stufen elektronischer Geschäftsprozesse eingesetzt werden, wodurch die Transaktionskosten gesenkt und der elektronische Geschäftsverkehr insgesamt beschleunigt und vereinfacht wird (vgl. [30], S. 548).     

Concurrent radiochemotherapy for patients with stage III non-small-cell lung cancer (NSCLC): long-term results of a phase II study

The distribution of estrogen and progesterone receptors (ER, PR) was assessed in the primary tumour in 1335 of 2704 (49%) consecutive new breast carcinoma patients (HORMREC). In a subgroup of 757 radically treated patients without systemic adjuvant treatment (RADOP) the relation of the ER and PR content to relapse and survival was evaluated. Three levels were defined for ER: ER-: <10 fmol/mg protein, ER+: moderate ER content >/= 10-99 fmol/mg protein, and high ER content >/= 100 fmol/mg protein. In 1288 patients of the HORMREC group who were evaluable for ER, 1061 (82%) had ER+ tumours, 685 (65%) of moderate content and 376 (35%) of high content, respectively. Among 917 patients, evaluable for PR, 723 (79%) tumours were PR+ (>/= 20 fmol/mg protein), of them 352 (49%) with a moderate content (>/= 20-99 fmol/mg protein) and 371 (51%) with a high content ( >/= 100 fmol/mg protein). The median ER content was significantly increased among the post-menopausal women as compared to the premenopausal women, whereas the median PR content showed no such differences. For the RADOP patients, no correlation between ER status and the first site of relapse was seen, whereas PR+ tumours tended to relapse more often locally than PR- tumours. In the univariate analysis the five-and 10-year tumour-related survival rates for all patients were not correlated with ER or PR positivity. One subgroup of patients with favourable outcome was identified on the basis of hormone receptors: Premenopausal women with tumours of moderately elevated ER content. In the multivariate analysis tumour size and axillary node status were the only independent predictors of survival. Measurements of hormone receptor status give weak prognostic information in radically treated patients with breast cancer as long as no adjuvant systemic treatment is applied. As todays' adjuvant treatment is based on the knowledge of hormone receptor status of the primary tumour, this information should be obtained routinely.     

Actions of A-131701, a novel, selective antagonist for alpha-1A compared with alpha-1B adrenoceptors on intraurethral and blood pressure responses in conscious dogs and a pharmacodynamic assessment of in vivo prostatic selectivity

A-131701 (3-[2-((3aR,9bR)-cis-6-methoxy-2,3,3a,4,5,9b, hexahydro-[1H]-benz[e]isoindol-2-yl)ethyl]pyrido [3',4': 4,5]thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione) is a novel compound previously shown to be selective for alpha-1a sites compared with alpha-1b adrenoceptors in radioligand binding studies and isolated tissue bioassays and to block canine urethral pressure (IUP) responses to exogenous alpha-1 adrenergic agonists to a greater extent than blood pressure responses. In conscious dogs in which IUP and mean arterial blood pressure (MABP) responses were measured periodically up to 24 hr, A-131701 blocked phenylephrine (PHE)-induced increases in IUP to a greater extent than MABP responses, and the blockade of the IUP effects of PHE was significantly different from control for up to 12 hr after doses greater than 0.3 mg/kg p.o., whereas blood pressure effects were of a lesser extent and duration. In addition to the weak antagonism of PHE-induced blood pressure responses, A-131701 also exhibited minimal effects on basal blood pressure in the dog, unlike terazosin, doxazosin or tamsulosin. Pharmacokinetic analysis of plasma samples from dogs indicated that A-131701 had a half-life of 0.4 to 0.8 hr and a bioavailability of 30 to 50% in dogs. Somewhat longer half-lives were observed in rat and monkey, with bioavailability values in the 25 to 30% range. Evidence of nonlinearity of pharmacokinetics was obtained in dogs and monkeys. Pharmacodynamic analysis revealed differences between A-131701 and nonselective alpha-1 adrenoceptor antagonists in selectivity for prostatic versus vascular alpha-1 adrenoceptors based on either extent or duration of blockade, which were either similar to or superior to compounds such as tamsulosin or REC 15/2739. These data demonstrate that A-131701 selectively blocks canine prostatic alpha-1 adrenoceptors for prolonged periods compared with MABP responses in vivo. Therefore, A-131701 should have clinical utility in the pharmacotherapy of benign prostatic hyperplasia.     

Acid‐formed pectin gel delays major incomplete kiwi fruit allergen Act c 1 proteolysis in in vitro gastrointestinal digestion

BACKGROUND: It is thought that food sensitisers must be able to reach the intestine in order to sensitise patients. Pectin is a gel‐forming plant polysaccharide that can protect allergens from in vivo gastric digestion and in vitro pepsin digestion. The aim of this study was to examine if pectin gel formed in the acidic environment of the stomach can protect labile allergen from in vitro gastrointestinal digestion. RESULTS: Pectin forms a gel in the acidic conditions of gastric fluid up to a concentration of 1.0 ± 0.14 g L^?1. Four allergenic fruits (kiwi, cherry, apple and banana) form gels in the same manner at the dilutions 14.8 ± 0.4; 8.4 ± 0.2, 9.4 ± 0.35 and 29.1 ± 0.2, respectively. The time necessary for dissolution of 50 g L^?1 pectin gel in intestinal fluid was found to be 70 ± 0.2 min. Pectin gel formed in situ was able to protect Act c 1 from pepsin digestion for 1 h and from further intestinal digestion for one additional hour. CONCLUSION: Pectin gel in an acidic environment protects Act c 1 from pepsin digestion and dissolves slowly in the slightly basic environment of the intestine allowing the survival of fruit allergen for additional time and possible interaction with the gut immune system. Copyright © 2008 Society of Chemical Industry     

Removal of N-terminal peptides from β-lactoglobulin by proteolytic contaminants in a commercial phenol oxidase preparation

The use of enzymes may improve the functional properties of various food ingredients. The aim of this study was to examine the effects of proteolytic contaminants in phenol oxidases on β-lactoglobulin (BLG). In the presence of Trametes versicolor laccase and Agaricus bisporus tyrosinase, both variants of BLG (A and B) underwent removal of a peptide from the N-terminus. The truncated forms were more susceptible to digestion by pepsin. The truncation of BLG resulted from contaminating proteases and not due to the action of phenol oxidases. The removal of N-terminal peptides proceeded quickly, while the rest of the globular protein remained resistant to proteolysis for up to 3 h. In the case of the application of enzymes in food bioprocessing, it may be important to carefully monitor the effects of contaminating proteases in enzyme preparations used.     

Nanotechnologie im Bauwesen

Nanotechnology in Construction Engineering In general, nanotechnology comprises the development, production and application of materials yielding novel functionalities and performances. In the construction industry and materials research nanotechnology can be utilized for a variety of areas of application, such as the optimisation of material properties, the prevention of damages and the implementation of new functionalities. This article gives an overview of areas in the construction sector where nanotechnology gains prominently of significance, such as cementitious binders, façades, windows and glazing, fire protection, interior decoration and infrastructure buildings. Furthermore, actual scientific research activities in the field of building materials on a nano‐scale performed by the Federal Institute for Materials Research and Testing (BAM) in Berlin are being presented. The research activities relate to the modification of hydrate phases in ultra high performance concrete (UHPC) and to the enhancement of performance of anti‐graffiti‐systems.     

Lineare Wärmebrücken in vakuumgedämmten Konstruktionen

Linear thermal bridges in vacuum insulated constructions. Continuously rising demands on the structural thermal insulation of heated buildings lead under certain conditions to high efficient insulation materials, which achieve its efficiency by using the vacuum technology. Inside these elements there is a medium vacuum that has to be durable to guarantee the excellent heat insulating characteristic. For that purpose a non‐permeable enveloping of the core material is essential, which breeds around the element edges increased heat losses, especially referring to the element joints concerning large vacuum insulated areas. This paper quantifies these additional heat losses for different constructions based on measurements.     

Side‐Directed Transfer and Presystemic Metabolism of Selenoneine in a Human Intestinal Barrier Model

Scope : Selenoneine, a recently discovered selenium (Se) species mainly present in marine fish, is the Se analogue of ergothioneine, a sulfur‐containing purported antioxidant. Although similar properties have been proposed for selenoneine, data on its relevance to human health are yet scarce. Here, the transfer and presystemic metabolism of selenoneine in an in vitro model of the human intestinal barrier are investigated. Methods and results : Selenoneine and the reference species Se‐methylselenocysteine (MeSeCys) and selenite are applied to the Caco‐2 intestinal barrier model. Selenoneine is transferred in higher amounts, but with similar kinetics as selenite, while MeSeCys shows the highest permeability. In contrast to the reference species, transfer of selenoneine is directed toward the blood side. Cellular Se contents demonstrate that selenoneine is efficiently taken up by Caco‐2 cells. Moreover, HPLC/MS‐based Se speciation studies reveal a partial metabolism to Se‐methylselenoneine, a metabolite previously detected in human blood and urine. Conclusions : Selenoneine is likely to pass the intestinal barrier via transcellular, carrier‐mediated transport, is highly bioavailable to Caco‐2 cells and undergoes metabolic transformations. Therefore, further studies are needed to elucidate its possible health effects and to characterize the metabolism of selenoneine in humans.     

Acid Extraction from Liquid Phase Pyrolysis Oil Using Cyanex®923 and Subsequent Solvent Regeneration

Liquid phase pyrolysis (LPP) oil, an intermediate from biofuel production using second‐generation biomass, is a promising source of biobased platform chemicals like acetic acid, however, displaying a complex, multicomponent mixture. Reactive extraction with Cyanex®923 was investigated for selective recovery of acids and subsequent solvent regeneration in distillation at 200 mbar. In a three‐stage extraction 81 % of acids were removed from the LPP oil without loss of Cyanex®923 to the raffinate. Solvent regeneration efficiency of acids was up to 99.7 % with mainly acids and water in the distillate.