In vitro evaluation of the mutagenic and carcinogenic power of high purity zirconia ceramic

Tetragonal zirconia polycrystal (TZP) is a new interesting ceramic for the manufacture of medical devices. Its wide use in orthopedic and odontoiatric implants was limited till now by the high chemical and radiochemical impurities of the raw materials. Purification processes now available allow to obtain high purity ceramic grade powders suitable for TZP ceramics manufacture, even if their possible mutagenic and transforming effects are still unclear. The aim of this work is to study in vitro the mutagenic and oncogenic effects of a new zirconia ceramic stabilized by yttria (Y-TZP). This ceramic was sintered from high purity powders obtained by a process developed under a project carried out within the Brite EuRam programme. For comparison, ceramics made from unpurified zirconia powder were also tested. Fibroblasts irradiated by a linear accelerator were used as positive control. The results obtained show that Y-TZP ceramic does not elicit either mutagenic or transforming effect on C3H/10T(1/2) (10T(1/2)) cells and demonstrate that ceramic from high purity powders can be considered suitable for biomedical applications from the point of view of the effects of its radioactive impurity content.     

Enthalpy of hydrogen bond formation in a protein-ligand binding reaction.

Parallel measurements of the thermodynamics(free-energy, enthalpy, entropy and heat-capacity changes) of ligand binding toFK506 binding protein (FKBP-12) in H2O and D2O have been performed in an effortto probe the energetic contributions of single protein-ligand hydrogen bondsformed in the binding reactions. Changing tyrosine-82 to phenylalanine inFKBP-12 abolishes protein-ligand hydrogen bond interactions in the FKBP-12complexes with tacrolimus or rapamycin and leads to a large apparent enthalpicstabilization of binding in both H2O and D2O. High-resolution crystallographicanalysis reveals that two water molecules bound to the tyrosine-82 hydroxylgroup in unliganded FKBP-12 are displaced upon formation of the protein-ligandcomplexes. A thermodynamic analysis is presented that suggests that the removalof polar atoms from water contributes a highly unfavorable enthalpy change tothe formation of C=O...HO hydrogen bonds as they occur in the processes ofprotein folding and ligand binding. Despite the less favorable enthalpy change,the entropic advantage of displacing two water molecules upon binding leads to aslightly more favorable free-energy change of binding in the reactions withwild-type FKBP-12.     

Effects of long-chain polyunsaturated fatty acid supplementation on fatty acid status and visual function in treated children with hyperphenylalaninemia

BACKGROUND: Children with phenylalanine-hydroxylase deficiency (type-I hyperphenylalaninemia, HPA) follow a low-phenylalanine diet, severely restricted in animal foods and long-chain polyunsaturated fatty acids (LCPUFA). Consequently, they have a poor LCPUFA status, particularly for docosahexaenoic acid (DHA). DHA is relevant to visual and neural development. OBJECTIVE: To investigate the effects of a 12-month supplementation with LCPUFA in a double-blind, placebo-controlled trial in treated children with HPA. STUDY DESIGN: Twenty children with well-controlled HPA were randomly allocated to receive either a fat supplement (supplying 26% as fatty acids including DHA, 8%) or a placebo. The fatty acid composition of erythrocyte lipids and the visual evoked potentials were measured at baseline and after 12 months of supplementation. Reference data were obtained from healthy children of comparable age. RESULTS: At baseline children with HPA had a poorer DHA status and prolonged P100 wave latencies than the reference group. At the end of the trial the LCPUFA group showed a significant increase in DHA levels of erythrocyte lipids. In the LCPUFA group P100 wave latency decreased and was negatively associated with the DHA changes. CONCLUSIONS: A balanced dietary supplementation with LCPUFA in children with HPA is associated with an increase of the DHA pool and improved visual function.     

Nitric oxide produced by the enterocyte is involved in the cellular regulation of ion transport

The role of nitric oxide (NO) in the intestinal basal ion transport and under conditions of enterotoxin-induced ion secretion is controversial. Namely it is not clear whether NO enhances or counteracts intestinal ion secretion and whether the effects on transport result from a direct interaction with the enterocyte. The cell origin of NO is also unclear. We have tested the hypothesis that NO produced by the enterocyte directly regulates ion transport processes either in basal condition or in response to cholera toxin-induced secretion. Electrical variables reflecting transepithelial ion transport were measured in Caco-2 cell monolayers mounted in Ussing chambers exposed to the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester, in the presence or absence of cholera toxin. cAMP concentrations were also measured. NO release was determined by nitrite-nitrate concentration. NO synthase activities were assayed by Western blot analysis. Nomega-nitro-l-arginine methyl ester had a secretory effect, as judged by increased basal short-circuit current and cAMP concentration. It also increased cholera toxin-induced electrical response and cAMP production. Either cholera toxin or the cAMP analog 8-bromo-cAMP induced a rapidly progressive and Ca2+-dependent increase in NO concentration, suggesting a homeostatic up-regulation of the constitutive form of NO synthase. Western blot analysis showed an increase in constitutive NO synthase enzyme isoform. These results indicate that the enterocyte regulates its own ion transport processes, either in basal condition or in the presence of active secretion, through the activation of a constitutive NO synthase-NO pathway, functioning as a braking force of cAMP-induced ion secretion.     

Growth hormone stimulates, through tyrosine kinase, ion transport and proliferation in human intestinal cells.

BACKGROUND: Growth hormone (GH) stimulates intestinal growth and differentiation and promotes water and ion absorption in the rat intestine. Epidermal growth factor has similar effects, which involve tyrosine kinase activity. The effects of growth hormone on ion transport and cell growth and the role of tyrosine kinase in these effects were examined in a human-derived intestinal cell line (Caco-2). METHODS: For transport study, electrical parameters were measured in human intestinal Caco-2 cell monolayers mounted in Ussing chambers. Cell growth was monitored by counting and 3H-thymidine incorporation in the presence and absence of growth hormone. The role of tyrosine kinase was investigated by using its specific inhibitor genistein. RESULTS: The addition of growth hormone induced a rapid, Cl- -dependent, decrease in short-circuit current without affecting tissue conductance, which is consistent with an anion-absorptive effect. Incubation with growth hormone increased cell count by 85% and 3H-thymidine incorporation by 64% versus the count in control specimens. The absorptive and trophic effects of growth hormone were dose-dependent, and the maximum effective concentration was identical for each effect. Genistein blocked the growth hormone effect on ion transport and cell growth. CONCLUSIONS: Growth hormone stimulates ion absorption and cell growth in human enterocytes. Both effects result from a direct growth hormone-enterocyte interaction, and both require tyrosine kinase activity. Growth hormone may have therapeutic potential in intestinal diseases characterized by epithelial atrophy and loss of water and electrolytes.     

Spigelian hernia: our experience during a decade

The Authors report a small series (three cases) of Spigelian hernias and underline the rarity of this pathology (0.2% in their series of hernias of the abdominal wall). They determine the anatomical features of the region, recall clinical features and discuss the most interesting points differential diagnosis and therapy.     

Lack of efficacy of Lactobacillus GG in reducing pulmonary exacerbations and hospital admissions in children with cystic fibrosis: A randomised placebo controlled trial

Background

Intestinal dysbiosis has been described in Cystic Fibrosis (CF) and probiotics have been proposed to restore microbial composition. Aim of the study was to investigate the effects of Lactobacillus rhamnosus GG (LGG) on clinical outcomes in children with cystic fibrosis (CF).