Quantification and biodegradability assessment of meso-2,3-dimercaptosuccinic acid adsorbed on iron oxide nanoparticles.

Many interesting applications of magnetic iron oxide nanoparticles (IONPs) have recently been developed based on their magnetic properties and promising catalytic activity. Depending on their intended use, such nanoparticles (NPs) are frequently functionalized with proteins, polymers, or other organic molecules such as meso-2,3-dimercaptosuccinic acid (DMSA) to improve their colloidal stability or biocompatibility. Although the coating strongly affects the colloidal properties and environmental behaviour of NPs, quantitative analysis of the coating is often neglected. To address this issue, we established an ion chromatographic method for the quantitative analysis of surface-bound sulfur-containing molecules such as DMSA. The method determines the amount of sulfate generated by complete oxidation of sulfur present in the molecule. Quantification of the DMSA content of DMSA-coated IONPs showed that reproducibly approximately 38% of the DMSA used in the synthesis was adsorbed on the IONPs. Tests for the biodegradability of free and NP-bound DMSA using a microbial community from a wastewater treatment plant showed that both free and NP-bound DMSA was degraded to negligible extent, suggesting long-term environmental stability of DMSA-coated IONPs.

Inosine monophosphate dehydrogenase activity in paediatrics: age-related regulation and response to mycophenolic acid.

PURPOSE: Since many drug targets and metabolizing enzymes are developmentally regulated, we investigated a potential comparable regulation of inosine 5'-monophosphate dehydrogenase (IMPDH) activity that has recently been advocated as a pharmacodynamic biomarker of mycophenolic acid (MPA) effects in the paediatric population. Since the field of pharmacodynamic monitoring of MPA is evolving, we also analyzed the response of IMPDH activity on MPA in children vs adolescents after renal transplantation. METHODS: We analyzed IMPDH activity in peripheral blood mononuclear cells (PBMCs) in 79 healthy children aged 2.0-17.9 years in comparison to 106 healthy adults. Pharmacokinetic/pharmacodynamic profiles of MPA and IMPDH over 6 or 12 h after mycophenolate mofetil dosing were performed in 17 paediatric renal transplant recipients. IMPDH activity was measured by HPLC and normalized to the adenosine monophosphate (AMP) content of the cells, MPA plasma concentrations were measured by HPLC. RESULTS: Inosine 5'-monophosphate dehydrogenase activity displayed a high inter-individual variability (coefficient of variation 40.2%) throughout the entire age range studied. Median IMPDH did not differ significantly in healthy pre-school children (82 [range, 42-184] µmol/s/mol AMP), school-age children (61 [30-153]), adolescents (83 [43-154]) and healthy adults (83 [26-215]). Similar to adults, IMPDH activity in children and adolescents was inversely correlated with MPA plasma concentration. CONCLUSIONS: In conclusion, our data do not show a pronounced developmental regulation of IMPDH activity in PBMCs in the paediatric population and there is a comparable inhibition of IMPDH activity by MPA in children and adolescents after renal transplantation.

Conduction at domain walls in oxide multiferroics.

Domain walls may play an important role in future electronic devices, given their small size as well as the fact that their location can be controlled. Here, we report the observation of room-temperature electronic conductivity at ferroelectric domain walls in the insulating multiferroic BiFeO(3). The origin and nature of the observed conductivity are probed using a combination of conductive atomic force microscopy, high-resolution transmission electron microscopy and first-principles density functional computations. Our analyses indicate that the conductivity correlates with structurally driven changes in both the electrostatic potential and the local electronic structure, which shows a decrease in the bandgap at the domain wall. Additionally, we demonstrate the potential for device applications of such conducting nanoscale features.

Serological association of beta and gamma human papillomaviruses with squamous cell carcinoma of the skin.

BACKGROUND: Cutaneous human papillomaviruses (HPVs) may play a role in the development of squamous cell carcinomas (SCC) of the skin. Objectives Available serological studies on HPV and skin SCC have analysed only few HPV types from the phylogenetic genus beta. The potential association of cutaneous HPV types from the genera alpha, gamma, mu and nu with skin SCC has not been thoroughly analysed so far. METHODS: Using multiplex serology, a method that allows analysing sera for antibodies to up to 100 different antigens simultaneously, we re-analysed an SCC case-control study in immunocompetent individuals (43 cases, 77 controls) for antibodies to L1 capsid proteins of 29 cutaneous and two mucosal HPV types from five different genera. RESULTS: Significantly increased SCC risks were observed for the beta HPV types 15, 17 and 38, as well as for the gamma HPV type 50, with type-specific odds ratios (ORs) ranging from 2.6 to 3.4. Significant associations were also found in cases of seropositivity for any type of the beta 2 species (OR 3.3, 95% confidence interval [CI] 1.2-8.7) and for any type of the gamma genus (OR 3.1, 95% CI 1.1-8.6). With regression models that included all HPV types and forward stepwise selection, two gamma HPV types (HPV 95, OR 25, 95% CI 1.2-509; HPV 50, OR 3.6, 95% CI 1.4-9.4) were each significantly associated with skin SCC. CONCLUSIONS: Our study confirms a possible role of cutaneous HPV in the development of skin SCC. Future studies should include skin HPV types from more than only the beta genus, especially gamma types.

Heimia salicifolia: a phytochemical and phytopharmacologic review.

Heimia salicifolia grows wild from Mexico to Argentina. The aerial parts have a wide folk reputation for antisyphilitic, sudorific, antipyretic, laxative and diuretic activity, and are reported to be useful in preparing post partum baths and to enhance wound healing. Its four most studied alkaloids are vertine, lyfoline, lythrine and nesodine. Structural relationships of the Heimia alkaloids and certain synthetic 4-arylquinolizidines are reviewed here. Preliminary clinical evaluation indicates that vertine and lythrine given orally appear to lack the psychodysleptic activity that has been touted for native brews said to incorporate H. salicifolia. Most of the animal studies discussed here have focused on the ataractic, antiinflammatory and antispasmodic potential of vertine and on the hydrodiuretic potential of lythrine and decine, a structurally related alkaloid found in Decodon verticillatus. The ataractic activity of vertine does not appear to be dependent on the depletion or blockade of catecholamines, while its antiinflammatory capacity seen in both exudative and immunologic systems seems to be dependent in part on an intact pituitary-adrenal system and in part on inhibition of prostaglandin synthase. The antisplasmodic activity of vertine has been demonstrated on many isolated tissues using different agonists, but appears to be largely musculotropic in nature. Only lythrine and decinine have been shown to be true hydrodiuretics and may prove to be useful in treating Addison's disease and general nephrosis. A number of synthetic 4-arylquinolizidines and related compounds appear to possess antiinflammatory potential.

Inhibition of synaptosomal high-affinity uptake of dopamine and serotonin by estrogen agonists and antagonists.

High-affinity uptake of dopamine and serotonin into a synaptosomal preparation from rat cerebral cortex was inhibited by a number of estrogen agonists and antagonists in vitro in a stereoselective and competitive manner. The most potent estrogenic inhibitors in the dopaminergic and serotonergic system were ethinylestradiol (KI = 558 nM) and 2-hydroxyethinylestradiol (KI = 226 nM), respectively. Structure-activity relationships are discussed and compared with the effects of estrogens on noradrenaline uptake. However, as all physiologically occurring estrogens inhibited amine uptake only in the micromolar concentration range it seems unlikely that this direct interaction of estrogen with the amine carrier is responsible for the changes in dopamine and serotonin uptake observed during the estrous cycle or after in vivo administration of estrogens and/or progesterone.

[Sector echocardiographic determination of the diameter of the large arteries of the heart in children]. / Sektorechokardiographische Durchmesserbestimmung der herznahen grossen Arterien bei Kindern.

We determined the end-diastolic and end-systolic diameters of the aortic root, ascending aorta, aortic arch, pulmonary trunk, and right pulmonary artery in infants and children with congenital heart disease by means of two-dimensional echocardiography. These measurements were compared to those obtained by angiocardiography in the same patients. We found an excellent correlation (r = 0.94 to 0.99) with a slope near to 1. In a second study, we measured echocardiographically the end-systolic diameters of the aortic root, ascending aorta, aortic arch, pulmonary trunk and right pulmonary artery in 87 healthy newborns, infants, children and adolescents and correlated these measurements with the body weight. We found a nonlinear correlation with the diameters being best described as a function of the natural logarithm of the body weight. We determined normal ranges containing 90% of all future normal observations with a confidence of 90%. These normal ranges may serve as basis for comparison of measurements of the same diameters in children with heart disease.

The phenyl- and biphenyl-quinolizidines of in-vitro-grown Heimia salicifolia.

Under the conditions delineated in this paper, alkaloid synthesis was not detectable in heterotrophic callus and suspension cultures of Heimia salicifolia. However, in vitro-grown shoots are active in alkaloid biosynthesis, yielding the biphenylquinolizidine lactones vertine (1), lytrine (5), and lyfoline (7), the ester alkaloids demethoxyabresoline (14) and epidemethoxylabresoline (11), the phenylquinolizidinols demethyllasubine-I (10) and demethyllasubine-II (12), and several minor alkaloids that had not been previously shown to occur in H. salicifolia.

The phenylquinolizidines of the seedlings of Heimia salicifolia.

Two isomeric 2-hydroxy-4-(3-hydroxy-4-methoxyphenyl)quinolizidines (3 and 9a), differing in the configuration of the bridgehead carbon, have been isolated from 5 to 10-day-old seedlings of Heimia salicifolia. The phenylquinolizidol with the cis ring juncture is shown to exist, in solution, as an equilibrium of conformers. 2-Keto-4-(3-hydroxy-4-methoxyphenyl)quinolizidine (5) has been isolated from the seedlings by radioactive dilution.