An optimized reverse-phase high performance liquid chromatographic method for evaluating percutaneous absorption of glucosamine hydrochloride

A relatively simple, selective, precise and accurate high performance liquid chromatography (HPLC) method based on a reaction of phenylisothiocyanate (PITC) with glucosamine (GL) in alkaline media was developed and validated to determine glucosamine hydrochloride permeating through human skin in vitro. It is usually problematic to develop an accurate assay for chemicals traversing skin because the excellent barrier properties of the tissue ensure that only low amounts of the material pass through the membrane and skin components may leach out of the tissue to interfere with the analysis. In addition, in the case of glucosamine hydrochloride, chemical instability adds further complexity to assay development. The assay, utilising the PITC-GL reaction was refined by optimizing the reaction temperature, reaction time and PITC concentration. The reaction produces a phenylthiocarbarnyl-glucosamine (PTC-GL) adduct which was separated on a reverse-phase (RP) column packed with 5 mu m ODS (C-18) Hypersil particles using a diode array detector (DAD) at 245 nm. The mobile phase was methanol-water-glacial acetic acid (10:89.96:0.04 v/v/v, pH 3.5) delivered to the column at 1 ml min(-1) and the column temperature was maintained at 30 degrees C Using a saturated aqueous solution of glucosamine hydrochloride, in vitro permeation studies were performed at 32 +/- 1 degrees C over 48 h using human epidermal membranes prepared by a heat separation method and mounted in Franz-type diffusion cells with a diffusional area 2.15 +/- 0.1 cm(2). The optimum derivatisation reaction conditions for reaction temperature, reaction time and PITC concentration were found to be 80 degrees C, 30 min and 1 % v/v, respectively. PTC-Gal and GL adducts eluted at 8.9 and 9.7 min, respectively. The detector response was found to be linear in the concentration range 0-1000 mu g ml(-1). The assay was robust with intra- and inter-day precisions (described as a percentage of relative standard deviation, %R.S.D.) < 12. Intra- and inter-day accuracy (as a percentage of the relative error, %RE) was <=-5.60 and <=-8.00, respectively. Using this assay, it was found that GL-HCI permeates through human skin with a flux 1.497 +/- 0.42 mu g cm(-2) h(-1), a permeability coefficient of 5.66 +/- 1.6 x 10(-6) cm h(-1) and with a lag time of 10.9 +/- 4.6 h. (c) 2005 Elsevier B.V. All rights reserved.

Measurement of apolipoprotein B-48 in the Svedberg flotation rate (Sf) > 400, Sf 60 – 400 and Sf 20 – 60 lipoprotein fractions reveals novel findings with respect to the effects of dietary fatty acids on triacylglycerol-rich lipoproteins in postmenopausal women

The present study was designed to examine whether the type of fat ingested in an initial test meal influences the response and density distribution of dietary-derived lipoproteins in the Svedberg flotation rate (Sf)>400, Sf 60 - 400 and Sf 20 - 60 lipoprotein fractions. A single-blind randomized within-subject crossover design was used to study the effects of palm oil, safflower oil, a mixture of fish and safflower oil, and olive oil on postprandial apolipoprotein (apo) B-48, retinyl ester and triacylglycerol responses in each lipoprotein fraction following an initial test meal containing one of the oils and a second standardized test meal. For all dietary oils, late postprandial (300min) concentrations of triacylglycerol and apo B-48 were significantly higher in the Sf 60 - 400 fraction than in the Sf>400 fraction (P<0.02). Significantly greater apo B-48 incremental areas under the curve (IAUCs) were also observed in the Sf 60 - 400 fraction than in the Sf>400 fraction following palm oil, safflower oil and olive oil (P<0.04), with a similar non-significant trend for fish/safflower oil. Olive oil resulted in a significantly greater apo B-48 IAUC in the Sf>400 fraction (P<0.02) than did any of the other dietary oils, as well as a tendency for a higher IAUC in the Sf 60 - 400 fraction compared with the palm, safflower and fish/safflower oils. In conclusion, we have found that the majority of intestinally derived lipoproteins present in the circulation following meals enriched with saturated, polyunsaturated or monounsaturated fatty acids are of the density and size of small chylomicrons and chylomicron remnants. Olive oil resulted in a greater apo B-48 response compared with the other dietary oils following sequential test meals, suggesting the formation of a greater number of small (Sf 60 - 400) and large (Sf>400) apo B-48-containing lipoproteins in response to this dietary oil.

Evaluation of two "integrated" polarimetric Quantitative Precipitation Estimation (QPE) algorithms at C-band

Two so-called “integrated” polarimetric rate estimation techniques, ZPHI (Testud et al., 2000) and ZZDR (Illingworth and Thompson, 2005), are evaluated using 12 episodes of the year 2005 observed by the French C-band operational Trappes radar, located near Paris. The term “integrated” means that the concentration parameter of the drop size distribution is assumed to be constant over some area and the algorithms retrieve it using the polarimetric variables in that area. The evaluation is carried out in ideal conditions (no partial beam blocking, no ground-clutter contamination, no bright band contamination, a posteriori calibration of the radar variables ZH and ZDR) using hourly rain gauges located at distances less than 60 km from the radar. Also included in the comparison, for the sake of benchmarking, is a conventional Z = 282R1.66 estimator, with and without attenuation correction and with and without adjustment by rain gauges as currently done operationally at Météo France. Under those ideal conditions, the two polarimetric algorithms, which rely solely on radar data, appear to perform as well if not better, pending on the measurements conditions (attenuation, rain rates, …), than the conventional algorithms, even when the latter take into account rain gauges through the adjustment scheme. ZZDR with attenuation correction is the best estimator for hourly rain gauge accumulations lower than 5 mm h−1 and ZPHI is the best one above that threshold. A perturbation analysis has been conducted to assess the sensitivity of the various estimators with respect to biases on ZH and ZDR, taking into account the typical accuracy and stability that can be reasonably achieved with modern operational radars these days (1 dB on ZH and 0.2 dB on ZDR). A +1 dB positive bias on ZH (radar too hot) results in a +14% overestimation of the rain rate with the conventional estimator used in this study (Z = 282R^1.66), a -19% underestimation with ZPHI and a +23% overestimation with ZZDR. Additionally, a +0.2 dB positive bias on ZDR results in a typical rain rate under- estimation of 15% by ZZDR.

The synthesis of dicobalt and dinickel complexes of trimethylsilylethynyl-1, 2-dihydrofullerene; characterisation by n.m.r. and structure of the first acyclic metal fullerene derivative: molecular structure of [η2-{2-H-1-(Me3SiC ≡ C)-C60}Ni2(η-C5H5)2]

The synthesis and characterisation of the complexes [η2-{2-H-1-(Me3SiC ≡ C)-C60}Co2(CO)6] (2)} and [η-2-{2-H-1-(Me3SiC ≡ C)-C60}Ni2η-C5H5)2] (3)} is reported, together with a single-crystal molecular structure for (3). This provides the first structural data for an acyclic metal derivative of [60]-fullerene.

Configurational preferences of two 1,2-diamine adducts of bis(1-(2-thienyl)-4,4,4-trifluoro-1,3-butanedionato)cobalt(II)

The preparation, the IR and ligand field spectra and the structures of the mixed-ligand addition compounds [(N,N-dimethyl-1,2-diaminoethane)bis(1-(2-thienyl)-4,4,4-trifluoro-1,3-butanedionato)cobalt(II)], [Co(thtf)2me2en], and [(N,N,N′,N′-tetramethyl-1,2-diaminoethane)bis(1-(2-thienyl)-4,4,4-trifluoro-1,3-butanedionato)cobalt(II)], [Co(thtf)2me4en], are reported. The structures were determined by single crystal X-ray diffraction analysis (monoclinic, space group P21/c, Z=4 with a=10.708(6), b=19.531(6), c=13.352(6) Å, β=111.64(10)°, R1=0.0642 and wR2=0.1719 for [Co(thtf)2(me2en)] and a=12.033(6), b=15.565(6), c=15.339(6) Å, β=92.57(6)°, R1=0.0612 and wR2=0.1504 for [Co(thtf)2me4en]). The structures are distorted octahedral and the shortest cobalt–cobalt separation distances are 5.388(2) Å in [Co(thtf)2me2en] and 8.675(3) Å in [Co(thtf)2me4en]. In both compounds the diamine molecules attain the gauche conformation. The U(Z,Z) conformation of the β-dione leads to a semi-chair conformation of the β-dionato chelate rings. The relative orientation of the groups attached to the β-dionato moiety depends on the extent of stereoelectronic effects the N-substitution of the diamine entails. In [Co(thtf)2me2en] the intraligand distance separating the trifluoromethyl carbon atoms is 5.281(18) Å while in [Co(thtf)2me2en] it increases to 8.338(9) Å. The cobalt–cobalt separation distance, the orientation of the chelate rings and the extent of N-substitution seem to affect hydrogen bonding. While in [Co(thtf)2me2en] inter- and intraligand hydrogen bonding is implicated, it is totally absent in [Co(thtf)2me4en].

Anticancer activity of organotin compounds. 2. Interaction of diorganotin dihalides with nucleic acid bases and nucleosides; the synthesis of adenine, adenosine and 9-methyladenine adducts

The syntheses of the complexes formulated as SnMe2Cl2(Ad)2 (I), SnMe2Cl2(Ado)2 (II), SnMe2Cl2- (9-MeAd)2 (III) [Ad = adenine, Ado = adenosine, 9-MeAd = 9-methyladenine] as well as the more unexpected SnPhCl2(OH)(Ad)2·3H2O (IV) and SnPhCl3(Ado)2 (V) by reaction of SnMe2Cl2 or SnPh2Cl2 with the appropriate bases in methanol is described. 1H NMR studies suggest that coordination is through the N-7 position of the adenine base.

Foehn jets over the Larsen C ice shelf, Antarctica

Previously unknown foehn jets have been identified to the east of the Antarctic Peninsula (AP) above the Larsen C Ice Shelf. These jets have major implications for the east coast of the AP, a region of rapid climatic warming and where two large sections of ice shelf have collapsed in recent years. During three foehn events across the AP, leeside warming and drying is seen in new aircraft observations and simulated well by the Met Office Unified Model (MetUM) at ∼1.5 km grid spacing. In case A, weak southwesterly flow and an elevated upwind inversion characterise a highly nonlinear flow regime with upwind flow blocking. In case C strong northwesterly winds characterise a relatively linear case with little upwind flow blocking. Case B resides somewhere between the two in flow regime linearity. The foehn jets – apparent in aircraft observations where available and MetUM simulations of all three cases – are mesoscale features (up to 60 km in width) originating from the mouths of leeside inlets. Through back trajectory analysis they are identified as a type of gap flow. In cases A and B the jets are distinct, being strongly accelerated relative to the background flow, and confined to low levels above the Larsen C Ice Shelf. They resemble the ‘shallow foehn’ of the Alps. Case C resembles a case of ‘deep foehn’, with the jets less distinct. The foehn jets are considerably cooler and moister relative to adjacent regions of calmer foehn air. This is due to a dampened foehn effect in the jet regions: in case A the jets have lower upwind source regions, and in the more linear case C there is less diabatic warming and precipitation along jet trajectories due to the reduced orographic uplift across the mountain passes.

Entre histoire et fiction: la représentation du règne d'Arthur dans le manuscrit enluminé du Brut en prose, Londres, Lambeth Palace 6 (c. 1480)

The manuscript London, Lambeth Palace 6, contains the Middle English prose Brut, a text which benefited from a great popularity throughout the fifteenth century. It was copied by an English scribe and richly illuminated by the Master of Edward IV and his assistants at Bruges around 1480. This article studies the representation and integration of the reign of Arthur in the historical framework of the Brut or Chronicles of England, including its fictional aspects: Arthur emerges as a historical character but also as a chivalric and mythical figure. The analysis covers the miniatures ranging from the plot leading to the conception of Arthur to the end of his reign (fols. 36-66). The textual and iconographic choices of the prose Bruts are highlighted by comparisons with Geoffrey of Monmouth’s Historia Regum Britanniae, Wace’s Brut, and later prose rewritings in the Lancelot-Grail romance cycle, especially Merlin and its Vulgate Sequel. They show the continuous interest raised by Arthur in the aristocratic and royal circles of late fifteenth century England and the relationship be¬tween continental and insular historiographical, literary and artistic traditions.