Isolation and structure determination of a tetrameric sulfonyl dilithio methandiide in solution based on crystal structure analysis and 6Li/13C NMR spectroscopic data.

Dilithio sulfonyl methandiides are a synthetically and structurally highly interesting group of functionalized geminal dianions. Although very desirable, knowledge of the structure of dilithio methandiides in solution was lacking up to now. Herein, we describe the isolation and determination of the structure of tetrameric dilithio (trimethylsilyl)(phenylsulfonyl) methandiide in solution and in the crystal. The elucidation of the structure of the tetramer is based on crystal structure analysis and 13C/6Li NMR spectroscopic data. A characteristic feature of the structure of the tetramer is the C 2 symmetric C-Li chain, composed of four doubly Li-coordinated dianionic carbon and five Li atoms. Three Li atoms are devoid of a contact to a dianionic C atom. The tetramer, the dianionic C atoms of which undergo fast exchange, is in THF solution in fast equilibrium with a further aggregate, which is stable only at low temperatures.

Crystal structure of mono[3-(2-imidazolylthio)]-altro-beta-cyclodextrin: elliptical distortion of the cavity and unique 'Yin-Yang' stacking.

The title compound is elliptically distorted due to the unusual 1C4 geometry of the altrose portion. In packing, a unique fourfold helical structure is elaborated with head-to-head dimers as the repeating motif. The imidazolyl moieties mutually reside on each other's cavities thereby resembling the Yin-Yang type balancing of antagonisms.

Biodegradable microparticles for sustained release of a new GnRH antagonist--part I: Screening commercial PLGA and formulation technologies.

The formulation of a new GnRH antagonist (degarelix) in biodegradable poly(DL-lactide-co-glycolide) (PLGA) microparticles was investigated for the development of a 3-month sustained release formulation to treat prostate cancer. The aim was to screen formulation technologies and distinct copolymers to produce microparticles (MP) of different types with good entrapment efficiency (>85%) and peptide purity (>95%) after gamma sterilization. Basically, three types of degarelix-loaded MP (4, 8 and 16% w/w nominal content) were produced with solvent and non-solvent technologies, namely double-emulsion solvent evaporation, spray-drying and two extrusion methods. Besides composition, commercial copolymers differing in residual monomer content and functional group at the carboxylic terminus (acid or ester) were characterized and employed. Peptide loading capacity and purity, as well as shape, size characteristics, and porosity of the produced microparticles were discussed in relation to technology and copolymer choice. Spray-drying and micro-extrusion were the two preferred formulation technologies because of higher entrapment efficiency and better preservation of peptide purity during production and gamma-sterilization. The impact of formulation technologies on the MP characteristics overwhelmed the impact of copolymer selection. Nevertheless, one particular polymer was discarded since it was more susceptible towards radiolytic degradation. The resulting degarelix-MP will be tested in a biological assay for selection of the formulation based on performance.

Biodegradable PLGA microparticles for sustained release of a new GnRH antagonist: part II. In vivo performance.

Poly (DL-lactide-co-glycolide) microparticles (MP) containing a highly potent peptidic gonadotropin releasing hormone antagonist (degarelix) of interest in the prostate cancer indication were screened for biological performance. Efficacy was tested in a castrated male rat model at 3 doses (0.4, 1.0 and 1.5 mg/kg) and assessed as inhibition of luteinizing hormone (LH) secretion. When increasing the dose, onset of inhibition was faster, inhibition was more intense, and duration of action was prolonged. The MP type was also highly influent. If spray-dried and microextrusion particles exhibited comparable potencies, double emulsion microspheres were significantly less potent, both for onset and duration of inhibition. Interestingly, for the latter type it was found that the degarelix fraction released upon reconstitution in the solution for injection was significantly lower (max 0.3%), in comparison to spray-dried MP (max 2%) or microextrusion (max 4%). With the three types of particles, increasing peptide content was detrimental for duration of action, but only little difference was noticed between particles based on different polymers. At 1.5 mg/kg, LH inhibition was achieved over 36 days with spray-dried MP based on 75/25 lactate/glycolate copolymer. This was superior by 1 week to the performance of unformulated degarelix given at the same dose.

ECG on the road: robust and unobtrusive estimation of heart rate.

Modern automobiles include an increasing number of assistance systems to increase the driver's safety. This feasibility study investigated unobtrusive capacitive ECG measurements in an automotive environment. Electrodes integrated into the driving seat allowed to measure a reliable ECG in 86% of the drivers; when only (light) cotton clothing was worn by the drivers, this value increased to 95%. Results show that an array of sensors is needed that can adapt to the different drivers and sitting positions. Measurements while driving show that traveling on the highway does not distort the signal any more than with the car engine turned OFF, whereas driving in city traffic results in a lowered detection rate due to the driver's heavier movements. To enable robust and reliable estimation of heart rate, an algorithm is presented (based on principal component analysis) to detect and discard time intervals with artifacts. This, then, allows a reliable estimation of heart rate of up to 61% in city traffic and up to 86% on the highway: as a percentage of the total driving period with at least four consecutive QRS complexes.

Influence of heating car seats on scrotal temperature.

OBJECTIVE: To evaluate the influence of a heated versus an unheated car seat on scrotal temperature under standardized experimental conditions. DESIGN: Controlled clinical study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Thirty volunteers without a history of infertility and with a normal andrological examination. INTERVENTION(S): Scrotal temperatures were measured every minute with a portable data recorder connected to two thermistor temperature sensors, which were attached on either side of the scrotum. All volunteers started the experiment at the same time of day wearing standardized cotton wool trousers and shirts fitting to body size. Each volunteer performed two periods of 90 minutes in a randomized manner on either the heated or unheated car seat. RESULT(S): At the end of the sitting periods scrotal temperatures were significantly higher using the heated car seat versus the unheated seat (left scrotal side: 0.5 degrees C; right scrotal side: 0.6 degrees C). Maximum values recorded during sitting alone were exceeded on the heated seat already after one-third of the exposure time. CONCLUSION(S): The present study suggests that the frequent use of a heated car seat represents an additional scrotal, and consequently, testicular heat stress factor to that which is present by merely sitting for long periods.