Increased Bone Resorption during Lactation in Pycnodysostosis

Pycnodysostosis, a rare autosomal recessive skeletal dysplasia, is caused by a deficiency of cathepsin K. Patients have impaired bone resorption in the presence of normal or increased numbers of multinucleated, but dysfunctional, osteoclasts. Cathepsin K degrades collagen type I and generates N-telopeptide (NTX) and the C-telopeptide (CTX) that can be quantified. Levels of these telopeptides are increased in lactating women and are associated with increased bone resorption. Nothing is known about the consequences of cathepsin K deficiency in lactating women. Here we present for the first time normalized blood and CTX measurements in a patient with pycnodysostosis, exclusively related to the lactation period. In vitro studies using osteoclasts derived from blood monocytes during lactation and after weaning further show consistent bone resorption before and after lactation. Increased expression of cathepsins L and S in osteoclasts derived from the lactating patient suggests that other proteinases could compensate for the lack of cathepsin K during the lactation period of pycnodysostosis patients.     

Gut Microbial Metabolites of Polyunsaturated Fatty Acids Correlate with Specific Fecal Bacteria and Serum Markers of Metabolic Syndrome in Obese Women

The aim of this human study was to assess the influence of prebiotic-induced gut microbiota modulation on PUFA-derived bacterial metabolites production. Therefore, we analyzed the circulating fatty acid profile including CLA/CLnA in obese women treated during 3 months with inulin-type fructan prebiotics. In these patients, we had already determined gut microbiota composition by phylogenetic microarray and qPCR analysis of 16S rDNA. Some PUFA-derived bacterial metabolites were detected in the serum of obese patients. Despite the prebiotic-induced modulation of gut microbiota, including changes in CLA/CLnA-producing bacteria, the treatment did not impact significantly on the circulating level of these metabolites. However, some PUFA-derived bacterial metabolites were positively correlated with specific fecal bacteria (Bifidobacterium spp., Eubacterium ventriosum and Lactobacillus spp.) and inversely correlated with serum cholesterol (total, LDL, HDL). These correlations suggest a potential beneficial effect of some of these metabolites but this remains to be confirmed by further investigation.     

Synthesis, Autoorganization and Reactivity of Amphiphilic Derivatives of 1-Aminoisoindole in Water and Formamide

In this work, we present the synthesis of cationic surfactants based on 1-aminoisoindole. The physico-chemical properties were studied by conductometry, tensiometry, dynamic light scattering and transmission electron microscopy in water and in formamide. The reactivity of these novel surfactants has been studied at concentrations below and above critical aggregation concentrations (CAC) and it was found that reactions can proceed in structured media without the addition of other catalysts.     

Vitamin E inhibits fish oil-induced hyperlipidemia and tissue lipid peroxidation in hamsters

Previous research has linked hyperlipidemia with increased serum concentrations of lipid peroxidation products; however, a specific association between diet-induced oxidative stress and hyperlipidemia has not been studied. In the present study, the relationship between tissue lipid peroxidation and hyperlipidemia induced by ingestion of fish oil was examined. In Experiment 1, male Golden Syrian hamsters were fed semipurified diets composed of 1.6 wt% safflower oil plus 15.0 wt% of either butterfat (BF), safflower oil (SAFF), or high-cholesterol menhaden oil [MHO(H-CHOL)] semipurified diets for 27 d. The cholesterol contents of the diets were adjusted to 0.088%. The MHO(H-CHOL)-fed hamsters exhibited higher serum concentrations of total cholesterol, triglycerides, apolipoprotein B, and lipid peroxides when compared to the BF and SAFF diet groups. In a further study (Experiment 2), hamsters were fed for 27 d three dietary treatments: (i) MHO(H-CHOL) with no vitamin E content; (ii) a low-cholesterol menhaden oil containing high concentrations of vitamin E (2.5 mg tocopherol/g oil or dietary concentrations of 375 mg/kg) [MHO(L-CHOL)+E]; and (iii) the MHO(L-CHOL+E) with added cholesterol (595 mg/kg) [MHO(L-CHOL)+CHOL+E] to match the cholesterol content of the MHO(H-CHOL). The MHO(L-CHOL)+E and MHO(L-CHOL)+CHOL+E diet groups showed lower concentrations of serum cholesterol, triglycerides, and hepatic lipid peroxides than the MHO(H-CHOL)-treated group. Moreover, in contrast to the hypercholesterolemia caused by the MHO(H-CHOL) feeding, the MHO(L-CHOL)+E and MHO(L-CHOL)+CHOL+ E diets did not show a serum cholesterol-elevating action. This study supports the hypothesis that oxidative stress in the Syrian hamster could play a causal role in dietary-induced hyperlipidemia which can be inhibited by high vitamin E intake.     

Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

A multiple narrative approach to information systems failure: a successful system that failed

We discuss the introduction of an information system where the dominant coalition claimed project success. While the key users did not use the system as intended and the project goals were not achieved, the project committee reported success to the top management board. Using a multi-methodological approach, we can follow how different stakeholders attributed different meanings to the system introduced over time. The rhetorical tools used are analysed using a narrative methodology. We draw on the social construction of technology and use the concept of relevant social groups to understand the different interests influencing the organisational dynamics. We complement this approach by employing the concepts of organisational power and cultural fit between the new system and the different subcultures. We found that this multiple approach explains well how the acceptance of the new software processes was interpreted differently within the organisation, and also by the software supplier. Although limited, our case study reveals the process of socially constructing the success or failure of an information system using this multiple research approach. We compare our results with the literature on IS failures and we consider the value of combining constructionist and critical approaches through a narrative methodology.     

2,2 bis (4-ethynylphenyl) hexafluoropropane

Summary The 2,2 bis(4-ethynylphenyl)hexafluoropropane is prepared via an original synthesis's process using a substitution of 2,2 bis(4-triflatephenyl) hexafluoropropane by trimethylsilyl acetylene. In this process ZnO is used to remove the triflate anion formed during the reaction.This diacetylenic compound melts at 37–38°C, exhibits an onset of polymerization at 120°C. After thermal treatment at 250°C, the obtained network shows a softening point at 300°C. This network remains stable in air up to 435°C.     

Comparison of glycemic index of spelt and wheat bread in human volunteers

The assessment of the glycemic index (GI) seems to be an important parameter to take into account in order to better understand the physiologic effects of foods with high carbohydrate levels. Among cereals, which are major sources of carbohydrates, spelt (Triticum spelta L.) has been considered as particularly interesting from a nutritional point of view. The aim of this study was to evaluate in vivo the GI of white spelt bread in healthy subjects. The wheat (Triticum aestivum L.) white bread was used as reference food. To avoid differences in the production of both breads, spelt and wheat breads were baked under the same controlled conditions. Results showed that the glycemic profile of spelt white bread was not different from that of wheat white bread (GI of 93 ± 9). The area under the glycemic curve significantly and negatively correlated to fasting glycemia and carbohydrate intake during evening meals preceding the test. In conclusion, the glycemic response to spelt bread was similar to that of wheat bread. However, in order to avoid more inter-individual variability, our data supports the importance to propose standardised carbohydrate content for the last meal before evaluating the GI of food.     

Effects of alcohol on psychophysiological hyperreactivity to nonaversive and aversive stimuli in men at high risk for alcoholism.

Psychophysiological reactivity to nonaversive (1-KHz, 70-db tones) and aversive stimuli (shock) was examined in nonalcoholic men with multigenerational family histories (MFH) of alcoholism and family history negative (FH–) men, while sober and after consuming alcohol. In comparison with FH– Ss, sober MFH Ss had significantly larger skin conductance (SC) orienting responses (ORs), shorter OR latencies, slower habituation rates to the tones, and larger increases in heart rate and vasoconstriction to the shock. Alcohol dampened the magnitude of the SC-OR to the tones and the degree of cardiovascular reactivity to the shocks and increased the habituation rate to the tones in MFH Ss only. Alcohol consumption also increased the SC-OR recovery time in FH– Ss only. The MFH Ss' pattern of psychophysiological hyperreactivity is discussed in terms of a potential dysfunction in stimulus–response regulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)