Bio-inspired supramolecular materials by orthogonal self-assembly of hydrogelators and phospholipids.

The orthogonal self-assembly of multiple components is a powerful strategy towards the formation of complex biomimetic architectures, but so far the rules for designing such systems are unclear. Here we show how to identify orthogonal self-assembly at the supramolecular level and describe guidelines to achieve self-sorting in self-assembled mixed systems. By investigating multicomponent self-assembled systems consisting of low molecular weight gelators and phospholipids, both at a molecular and a supramolecular level, we found that orthogonal self-assembly can only take place if the entities assemble via a strong and distinct set of interactions. The resulting supramolecular architectures consist of fibrillar networks that coexist with liposomes and thereby provide additional levels of compartmentalization and enhanced stability as compared to self-assembled systems of gelators or phospholipids alone.

Cushing's disease and hypertension: in vivo and in vitro study of the role of the renin-angiotensin-aldosterone system and effects of medical therapy.

OBJECTIVE/METHODS: Cushing's disease (CD) is often accompanied by hypertension. CD can be treated surgically and, given the expression of somatostatin subtype 5 and dopamine 2 receptors by corticotroph pituitary adenomas, pharmacologically. Indeed, we recently observed that stepwise medical combination therapy with the somatostatin-analog pasireotide, the dopamine-agonist cabergoline, and ketoconazole (which directly suppresses steroidogenesis) biochemically controlled CD patients and lowered their blood pressure after 80 days. Glucocorticoids (GC) modulate the renin-angiotensin-aldosterone system (RAAS) among others by increasing hepatic angiotensinogen expression and stimulating mineralocorticoid receptors (MR). This study therefore evaluated plasma RAAS components in CD patients before and after drug therapy. In addition, we studied whether cabergoline/pasireotide have direct relaxant effects in angiotensin II (Ang II)-constricted iliac arteries of spontaneously hypertensive rats, with and without concomitant GR/MR stimulation with dexamethasone or hydrocortisone. RESULTS: Baseline concentrations of angiotensinogen were elevated, while renin and aldosterone were low and suppressed, respectively, even in patients treated with RAAS-blockers. This pattern did not change after 80 days of treatment, despite blood pressure normalization, nor after 4 years of remission. In the presence of dexamethasone, pasireotide inhibited Ang II-mediated vasoconstriction. CONCLUSIONS: The low plasma renin concentrations, even under RAAS blockade, in CD may be the consequence of increased GC-mediated MR stimulation and/or the elevated angiotensinogen levels in such patients. The lack of change in RAAS-parameters despite blood pressure and cortisol normalization suggests persisting consequences of long-term exposure to cortisol excess. Finally, pasireotide may have a direct vasodilating effect contributing to blood pressure lowering.

[Health care insurance for Africa]. / Een ziektekostenverzekering voor Afrika.

Long-term substantial development aid has not prevented many African countries from being caught in a vicious circle in health care: the demand for care is high, but the overburdened public supply of low quality care is not aligned with this demand. The majority of Africans therefore pay for health care in cash, an expensive and least solidarity-based option. This article describes an innovative approach whereby supply and demand of health care can be better aligned, health care can be seen as a value chain and health insurance serves as the overarching mechanism. Providing premium subsidies for patients who seek health care through private, collective African health insurance schemes stimulates the demand side. The supply of care improves by investing in medical knowledge, administrative systems and health care infrastructure. This initiative comes from the Health Insurance Fund, a unique collaboration of public and private sectors. In 2006 the Fund received Euro 100 million from the Dutch Ministry of Foreign Affairs to implement insurance programmes in Africa. PharmAccess Foundation is the Fund's implementing partner and presents its first experiences in Africa.

Ring closure dynamics of BTE-based photochromic switches: perfluoro- versus perhydrocyclopentene derivatives.

The switching behavior of 1,2-bis(5-phenyl-2-methylthien-3-yl)perfluorocyclopentene and its nonfluorinated (perhydro) analogue are compared. For both molecules, the dynamics after optical excitation can be separated into three regimes: preswiching due to excited state mixing; the ring closure itself; postswitching related to vibrational cooling. The fluorinated version switches faster than its nonfluorinated analogue by about a factor of 4.7. This is explained by electronic level shifts near the crossing region between the S(1) and S(0) potential energy surfaces. In the nonfluorinated molecule the various levels involved in the switching have well-separated transition frequencies, which allow for a clear interpretation of experimental data. Thus, the fluorinated molecule makes a better (more efficient and faster) switch, but the nonfluorinated molecule provides a better model system for fundamental studies.

One-way optoelectronic switching of photochromic molecules on gold.

We investigate photochromic molecular switches that are self-assembled on gold. We use two experimental techniques; namely, the mechanically controllable break-junction technique to measure electronic transport, and UV/Vis spectroscopy to measure absorption. We observe switching of the molecules from the conducting to the insulating state when illuminated with visible light (lambda=546 nm), in spite of the gold surface plasmon absorption present around this wavelength. However, we fail to observe the reverse process which should occur upon illumination with UV light (lambda=313 nm). We attribute this to quenching of the excited state of the molecule in the open form by the presence of gold.

Onset of lay related to multiphasic growth and body composition in White Leghorn pullets provided ad libitum and restricted diets.

Growth of the body as a whole and of parts of the reproductive tract of White Leghorn pullets that ate ad libitum and restricted diets were analyzed by a multiphasic growth function. Parameter estimates were related to onset of lay. Chemical body compositions at defined stages of pubertal growth were related to the development of the reproductive organs. Data of pullets that had been restricted in one of two rearing periods (0 to 6 and 7 to 18 wk of age) were used. In each period, pullets were fed a low-lysine diet or a daily restricted amount of feed, on a pair-gain basis. In all mathematical fits, a well distinguishable "pubertal body growth spurt" at around 19 wk of age was found. About 40 to 70% of total growth within this phase consisted of growth of the reproductive tract (the ovary covered 19 to 35%, the oviduct 15 to 23%, and the uterus 7 to 11% of total growth). Age at maximum gain of the pubertal body growth spurt was 20.1 wk for lysine-restricted pullets and 19.6 wk for feed-restricted pullets. This difference reflected differences in onset of lay (50% rate of lay) between lysine- and feed-restricted birds (22.3 and 21.6 wk, respectively). An interval of 14 to 15 d existed between maximum gain of the pubertal body growth spurt and onset of lay. It was suggested that the occurrence of the pubertal body growth spurt can serve as a predictor for subsequent onset of lay. Body composition at defined moments during the pubertal body growth spurt was calculated by interpolation from chemical analyses of Weeks 15, 18, 20, 22, and 24. Crude fat content in the body at start of the pubertal body growth spurt varied considerably between the feeding regimens (112 to 179 g). The fat-free body (consisting of CP, ash, and water) showed less variation between the treatments at this stage (807 to 870 g). It is concluded that a particular amount of fat-free tissue is critical in pullet development and may be required before sexual organ development starts.

Low-temperature scanning electron microscopy in fungus-nematode interaction.

A comparative study has been made of different preparation techniques used for the scanning electron microscope (SEM), with regard to their application to fungus-nematode interaction. The preparation of frozen-hydrated specimens of both healthy and Arthrobotrys-oligospora-infected second-stage larvae of the root-knot nematode (Meloidogyne sp.) is described, and the results are compared with those obtained by critical point-drying and freeze-drying. In all cases the frozen-hydrated specimens consistently showed the best preservation.

Melittin-induced changes of the macroscopic structure of phosphatidylethanolamines.

The binding of melittin to phosphatidylethanolamine model systems and its influence on the supramolecular organization of the lipid were investigated with binding assays, differential scanning calorimetry, 31P NMR, freeze-fracture electron microscopy, and small-angle X-ray scattering. The results are compared with binding to an analogous phosphatidylcholine and structural consequences thereof. Melittin binds with similar affinity to both lipid types in the liquid-crystalline state; at gel-phase temperatures, in contrast, interaction with phosphatidylethanolamine is much weaker and does not lead to the bilayer fragmentation observed for phosphatidylcholines. With regard to phosphatidylethanolamine polymorphism, it is shown that melittin acts as an inhibitor of HII-phase formation and as a stabilizer of the bilayer organization. It is demonstrated that the remarkable variety of effects of melittin on the polymorphism of different membrane phospholipids can be understood in a relatively simple concept, taking into account the relative position and the shape of the interacting components.

A temporal red-green opponent mechanism.

A mechanistic model is presented that describes the temporal behaviour of a red-green colour opponent channel such as has been investigated for the macaque monkey. The model incorporates luminance- and chromaticity-adaptation mechanisms. Receptive field properties such as retardation and attenuation of the surround signals with respect to the center signals of the colour opponent channel are also included. The model predicts temporal psychophysical chromaticity thresholds and temporal electrophysiological red-green colour opponent ganglion cell behaviour with a reasonable degree of success.

Interaction of melittin with negatively charged phospholipids: consequences for lipid organization.

A characterization of the structural alterations induced by melittin in model-membranes of dioleoylphosphatidic acid and egg phosphatidylglycerol is presented, based on the use of 31P-NMR, freeze-fracture electron microscopy and small angle X-ray scattering. In accordance with earlier findings on the cardiolipin-melittin system, melittin is found to have an inverted phase inducing effect on these negatively charged lipids, in contrast to the influence on zwitterionic phospholipids. In phosphatidic acid this is expressed in the formation of an HII phase; in phosphatidylglycerol a less ordered, non-lamellar structure with low water content is adopted.

Spectral sensitivity and wavelength discrimination of the human peripheral visual field.

Spectral sensitivity and wavelength discrimination are determined along the nasal horizontal meridian of the human peripheral retina. The target size as a function of eccentricity is varied according to a particular cortical magnification factor. Spectral sensitivity is measured by flicker photometry parameterized for the flicker frequency (10-20 Hz) and is found to be independent of the eccentricity (0-80 degrees) for 20-Hz flicker photometry after correction of the foveal spectral sensitivity for macular pigment absorption. This 20-Hz function is chosen as being representative for the peripheral luminous-efficiency function and is used in the wavelength-discrimination experiments. The peripheral retina can perform wavelength discrimination up to an eccentricity of 80 degrees. If field-size scaling according to the eccentricity-dependent cone density, the cortical magnification factor, or the reciprocal of the interganglion cell distance is applied, then wavelength-discrimination performance from 8 degrees to 80 degrees eccentricity is roughly the same. Foveal wavelength discrimination is considerably better than peripheral wavelength discrimination.