Biocompatible magnetic microspheres for Use in PDT and hyperthermia.

Loaded microspheres with a silicon (IV) phthalocyanine derivative (NzPC) acting as a photosensitizer were prepared from polyhydroxybutyrate-co-valerate (PHBHV) and poly(ecaprolactone) (PCL) polymers using the emulsification solvent evaporation method (EE). The aim of our study was to prepare two systems of these biodegradable PHBHV/PCL microspheres. The first one containing only photosensitizer previously incorporated in the PHBHV and poly(ecaprolactone) (PCL) microspheres and the second one with the post magnetization of the DDS with magnetic nanoparticles. Magnetic fluid is successfully used for controlled incorporation of nanosized magnetic particles within the micron-sized template. This is the first time that we could get a successful pos incorporation of nanosized magnetic particles in a previously-prepared polymeric template. This procedure opens a great number of possibilities of post-functionalization of polymeric micro or nanoparticles with different bioactive materials. The NzPC release profile of the systems is ideal for PDT, the zeta potential and the size particle are stable upon aging in time. In vitro studies were evaluated using gingival fibroblastic cell line. The dark citotoxicity, the phototoxicity and the AC magnetic field assays of the as-prepared nanomagnetic composite were evaluated and the cellular viability analyzed by the classical test of MTT.

The effects of extended-release niacin on carotid intimal media thickness, endothelial function and inflammatory markers in patients with the metabolic syndrome.

BACKGROUND: Niacin is an agent that significantly increases high-density lipoprotein cholesterol (HDL-C), but its effects on surrogate markers of atherosclerosis and inflammatory markers are less clear. We studied the effects of niacin on carotid intimal media thickness (IMT), brachial artery reactivity as well as markers of inflammation and the metabolic profile of patients with metabolic syndrome. METHODS AND RESULTS: Fifty patients with the metabolic syndrome (Adult Treatment Panel (ATP) III criteria) were randomised to either extended-release niacin (1000 mg/day) or placebo. After 52 weeks of treatment, there was a change of carotid IMT of +0.009 +/- 0.003 mm in the placebo group and -0.005 +/- 0.002 mm in the niacin group (p = 0.021 between groups). Endothelial function improved by 22% in the group treated with niacin (p < 0.001), whereas no significant changes were seen in the placebo group. High sensitivity C-reactive protein decreased by 20% in the group treated with niacin for 52 weeks (p = 0.013). Niacin increased HDL-C (p < 0.001) and decreased low-density lipoprotein cholesterol and triglycerides (p < 0.001) significantly, and there were no adverse effects on fasting glucose levels after 52 weeks of treatment. CONCLUSION: Extended-release niacin therapy effects a regression in carotid intimal medial thickness and improvement in metabolic parameters (increased HDL and reduced triglycerides). Furthermore, extended-release niacin may demonstrate an anti-atherogenic effect in the metabolic syndrome by improving endothelial function and decreasing vascular inflammation.

Study of the PVRL1 gene in Italian nonsyndromic cleft lip patients with or without cleft palate.

Nonsyndromic cleft lip with or without cleft palate (CL/P) is a complex genetic trait and little is known about its aetiology. Recent investigations on rare clefting syndromes provided interesting clues about genes involved in face development. The PVRL1 gene encodes nectin1, a cell-to-cell adhesion molecule. Mutations in its sequence have been shown to cause the rare autosomal recessive syndrome CL/P-ectodermal dysplasia syndrome (CLPED1), while heterozygosity for the mutation W185X seemed to increase the risk of non syndromic CL/P in a population from northern Venezuela. In the present study, we screened 143 Italian CL/P patients for mutations in PVRL1. Three rare sequence variants in exon 3 that create amino-acid changes were detected in a total of 7 patients. Two of these mutations were not found in a panel of 292 unaffected controls, while the third was found in two controls. This study describes new mutations that may represent genetic risk factors for CL/P. Even though a study to look at the effects of the mutations on nectin1 function was not feasible, supporting evidence was reported, thus confirming the involvement of PVRL1 in the aetiology of non-syndromic CL/P malformation.

Comparative distribution of vasopressin V1b and oxytocin receptor messenger ribonucleic acids in brain.

The comparative distributions of the vasopressin V1b receptor (V1bR) and the oxytocin receptor (OTR) messenger RNAs (mRNAs) are described in male rat brain using in situ hybridization histochemistry. V1bR transcripts were present in forebrain and hypothalamus and were less abundant in mid- and hindbrain regions, similar to the gradient observed with OTR transcripts. Microscopic analyses indicated that V1bR expressing cells typically demonstrated the morphology of neurons and confirmed V1bR gene expression in regions including the olfactory bulb, supraoptic, suprachiasmatic, and dorsomedial hypothalamic nuclei, piriform and entorhinal cortices, hippocampus, substantia nigra, and dorsal motor nucleus of the vagus. Most regions that expressed V1bR mRNA also expressed OTR mRNA, although OTR gene expression was much more extensive than that of the V1bR. V1bR and OTR mRNA distributions were distinct from each other and from that of the V1a receptor mRNA in brain. A few brain regions express only V1bR transcripts such as the dorsomedial hypothalamic nucleus and the external plexiform layer of the olfactory bulb. Other brain regions, such as the fields of Ammon's horn, the suprachiasmatic nucleus, the substantia nigra pars compacta, and the piriform cortex express mRNAs that encode all three receptor subtypes (V1a, V1b, and OTR), whereas brain areas including the red nucleus and supraoptic nucleus express V1bR and OTR transcripts only. These data suggest functional specialization of the V1b, OTR and V1a receptors in brain.

Communication between parents and deaf children: implications for social-emotional development.

Parent-child communication plays a central role in social growth, as it does in other domains of development. Over 90% of deaf children, however, have hearing parents who frequently do not have a fully effective means of communicating with them. This paper examines the role of effective parent-child communication in the social and emotional development of deaf children. Evidence concerning relations between early communication and social-emotional development of deaf children is reviewed, and superficial differences in the ways that parents interact with deaf versus hearing children are distinguished from differences that may have more significant and enduring effects. Hearing parents and their deaf children are found to develop alternative, often nonverbal, interaction strategies. Of primary interest is the extent to which those strategies have impact comparable to the strategies of hearing parents with hearing children or deaf parents with deaf children.

Determination of free and amidated bile acids by high-performance liquid chromatography with evaporative light-scattering mass detection.

A simple reverse phase high-performance liquid chromatographic method for a simultaneous analysis of free, glycine- and taurine-amidated bile acids is described. The resolution of ursodeoxycholic, cholic, chenodeocycholic, deoxycholic, and lithocholic acids, either free or amidated with glycine and taurine, is achieved using a C-18 octadecylsilane column (30 cm length, 4 micron particle size) with a gradient elution of aqueous methanol (65----75%) containing 15 mM ammonium acetate, pH 5.40, at 37 degrees C. The separated bile acids are detected with a new evaporative light-scattering mass detector and by absorbance at 200 nm. A complete resolution of the 16 bile acids, including the internal standard nor-deoxycholic acid, is obtained within 55 min. Using the light-scattering mass detector, amidated bile acids and, for the first time, free bile acids can be detected with similar detection limits in the order of 2-7 nmol. The new detector improves the baseline and the signal-to-noise ratio over the UV detection as it is not affected by impurities present in the samples with higher molar absorptivity than bile acids or by the change in the mobile phase composition during the gradient. The method fulfills all the standard requirements of precision and accuracy and the linearity of the mass detector is over 5 decade the detection limit. The new method has been used for the direct analysis of bile acid in stools and bile with only a preliminary clean-up procedure using a C-18 reverse phase extraction.

Hepatic uptake and biliary secretion of bile acids in the perfused rat liver.

Hepatic uptake and biliary secretion have been evaluated in the isolated perfused rat liver for cholic, chenodeoxycholic, ursodeoxycholic acid, both free and taurine-conjugated; the physicochemical properties of the bile acids have also been calculated and related to these experimental parameters. Cholic acid disappearance rate from the perfusate was the fastest, followed by that of ursodeoxycholic and chenodeoxycholic; it was also faster for taurine-conjugated bile acids than for their respective unconjugated forms. The recovery in bile was higher for conjugated than for unconjugated bile acids, and among each class, was higher for cholic than for chenodeoxycholic and ursodeoxycholic. The hepatic uptake correlated negatively (r = -0.99) with the bile acid lipophilicity, while the biliary secretion correlated with the solubility of the molecules. These results show the effect of the physicochemical properties of BA on their hepatic handling, at the physiological concentration of BA in the portal blood.