IL-6 Cytokine Family: A Putative Target for Breast Cancer Prevention and Treatment

The IL-6 cytokine family is a group of signaling molecules with wide expression and function across vertebrates. Each member of the family signals by binding to its specific receptor and at least one molecule of gp130, which is the common transmembrane receptor subunit for the whole group. Signal transduction upon stimulation of the receptor complex results in the activation of multiple downstream cascades, among which, in mammary cells, the JAK-STAT3 pathway plays a central role. In this review, we summarize the role of the IL-6 cytokine family—specifically IL-6 itself, LIF, OSM, and IL-11—as relevant players during breast cancer progression. We have compiled evidence indicating that this group of soluble factors may be used for early and more precise breast cancer diagnosis and to design targeted therapy to treat or even prevent metastasis development, particularly to the bone. Expression profiles and possible therapeutic use of their specific receptors in the different breast cancer subtypes are also described. In addition, participation of these cytokines in pathologies of the breast linked to lactation and involution of the gland, as post-partum breast cancer and mastitis, is discussed.     

Partial or total silylation of dextran with hexamethyldisilazane

The silylation reaction of dextran with 1,1,1,3,3,3-hexamethyldisilazane (HMDS) in DMSO was studied as the first step of the synthesis of new amphiphilic polyester-grafted dextrans. According to the experimental conditions, i.e. dextran molar weight, medium temperature and reaction time, HMDS/OH ratio, addition of a catalyst and co-solvent, partially or totally silylated dextrans were recovered. The highest silylation yields were obtained with the lowest molecular weight dextrans. The increase in temperature medium and/or reaction time, the presence of catalyst or co-solvent favored the protection yield. Whatever the dextran used, complete silylation of the polysaccharide chain could be achieved by adequate selection of the experimental conditions. The thermal properties of resulting silylated polysaccharides were investigated by temperature modulated DSC. It was observed that T_g values of partially silylated dextran were maintained between 120 and 140 °C, independently of the dextran molecular weight. Interestingly, DMSO proved to behave as an efficient plasticizer of (partially) silylated dextrans. The partially silylated dextrans were efficiently used as multifunctional macroinitiators for the controlled ring-opening polymerization (ROP) of lactone. The ROP was then promoted from the remaining hydroxyl groups in the presence of tin or aluminium activator. After polymerization and ultimate deprotection of the silylated dextran backbone, amphiphilic polyester-grafted dextrans were readily recovered.     

New light-sensitive nucleosides for caged DNA strand breaks

Phototriggered bod cleavage has found wide application in chemistry as well as in biology. Nevertheless, there are only a few methods available for site-specific photochemical induction of DNA strand scission despite numerous potential applications. In this study we report the development of new photocleavable nucleotides based on the photochemistry of o-nitrobenzyl esters. The light-sensitive moieties were generated through introduction of o-nitrophenyl groups at the 5'C position of the nucleoside sugar backbone. The newly synthesized, modified nucleosides were incorporated in oligonucleotides and are able to build stable DNA duplexes. In such a way modified oligonucleotides ca cleaved site-specifically upon irradiation with > 360 nm light with high efficiency. Furthermore, we show that these modifications can be bypassed in DNA synthesis promoted by Thermus aquaticus DNA polymerase.     

Influence of Process Parameters on the Morphology of Spray‐Dried BaCl2 Powders

Spray‐drying is an effective method for producing powder aggregates with controlled size and morphology. Here, we report on a systematic study aimed at determining how spray‐drying parameters such as nozzle temperature, gas flow, salt concentration and solution feed rate, influence the characteristics of BaCl₂ granules prepared from aqueous solutions. We correlate the granule characteristics to these conditions through the use of processing maps and modeling. It is found that well‐dispersed, high density and spherical aggregates, which are favorable for subsequent powder compaction and sintering, can be obtained within a limited range of processing conditions.     

Toluene degradation by a water/silicone oil mixture for the design of two phase partitioning bioreactors

Toluene degradation performances were studied in a 10 L Two-Phase Partitioning Bioreactor (TPPB).The liquid phase consisted of a mixture of water and PDMS 50 (PolyDiMethylSiloxane,i.e.silicone oil,viscosity of 46 maa·s) in the volume ratio of 75％/25％.Two series of experiments were carried out:in the first,the reactor was sequentially supplied with toluene whereas in the second,toluene was continuously supplied.Activated sludge from the wastewater treatment plant of Beaurade (Rennes,France) was used at an initial concentration of 0.5 dry mass g· (mixture L)-1.The elimination capacity (EC) was investigated as well as the change in biomass concentration over time.Toluene biodegradation was very efficient (removal efficiency,RE =100％) for toluene flows ranging from 0.2 to 1.2 ml· h-1,corresponding to elimination capacities of up to 104 g· m-3· h-1.For a toluene flow of 1.2 ml·h-1,the biomass concentration measured at the end of the experiment was 4.7 dry mass g.(mixture L)-1.The oxygen concentration in the liquid phase was clearly not a limiting factor in these operating conditions.Based on these results,an extrapolation leading to the design of a large-scale pilot TPPB can now be considered to study toluene degradation performances in industrial conditions.     

Salt-Sensitive Hypertension in GR+/− Rats Is Accompanied with Dysregulation in Adrenal Soluble Epoxide Hydrolase and Polyunsaturated Fatty Acid Pathways

Mutations within the glucocorticoid receptor (GR) gene locus lead to glucocorticoid resistance which is characterized by several clinical symptoms such as adrenal gland hyperplasia and salt-sensitive hypertension, although the underlying mechanisms are still unknown. We studied GR haploinsufficient (GR^+/−) Sprague Dawley rats which, on a standard diet, showed significantly increased plasma aldosterone and corticosterone levels and an adrenocortex hyperplasia accompanied by a normal systolic blood pressure. Following a high salt diet, these rats developed salt-sensitive hypertension and maintained elevated enzyme-soluble epoxide hydrolase (sEH) in adrenal glands, while sEH was significantly decreased in wild-type rats. Furthermore, GR^+/− rats showed dysregulation of the equilibrated linoleic and arachidonic acid pathways, with a significant increase of less active metabolites such as 8,9-DiHETrE. In Sprague Dawley rats, GR haploinsufficiency induced steroid disturbances, which provoked hypertension only in combination with high salt intake, which was accompanied by disturbances in sEH and fatty acid metabolism. Our results suggest that sEH inhibition could be a potential target to treat hypertension in patients with GR haploinsufficiency.     

Multivariate process trajectories for molecular description of MF thermal curing and correlation with hydrolytic stability

During curing of thermosetting resins the technologically relevant properties of binders and coatings develop. However, curing is difficult to monitor due to the multitude of chemical and physical processes taking place. Precise prediction of specific technological properties based on molecular properties is very difficult. In this study, the potential of principal component analysis (PCA) and principal component regression (PCR) in the analysis of Fourier transform infrared (FTIR) spectra is demonstrated using the example of melamine-formaldehyde (MF) resin curing in solid state. FTIR/PCA-based reaction trajectories are used to visualize the influence of temperature on isothermal cure. An FTIR/PCR model for predicting the hydrolysis resistance of cured MF resin from their spectral fingerprints is presented which illustrates the advantages of FTIR/PCR compared to the combination differential scanning calorimetry/isoconversional kinetic analysis. The presented methodology is transferable to the curing reactions of any thermosetting resin and can be applied to model other technologically relevant final properties as well.     

Enzymatischer Nachweis von Carbamat-Pesticiden auf impr?gnierten Cellulose-Platten

Zusammenfassung Ein Nachweis für Carbamat-Pesticide mittels Enzym-Inhibition auf imprägnierten Cellulose-Schichten wurde ausgearbeitet. Bei Celluloseschichten, die mit Äthylglykol, Triäthylglykol und,-Ogydipropionitril imprägniert waren, erwies sich die Kombination Schweineleberesterase/Indophenylacetat (als chromogenes Substrat) als besonders empfindlicher Nachweis. Die Nachweisempfindlichkeit wurde in Abhängigkeit von der Art des Enzympräparates, des Substrates, des pH, der Inhibitionszeit und -temperatur, der Schichtdicke und des Impriignierungsmittels untersucht.

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Enzymatic detection of carbamate pesticides on impregnated cellulose plates

Summary The detection of carbamate pesticides by an enzyme-inhibition method on impregnated (ethylene glycol, triethylene glycol,,-ogydipropionitrile) cellulose thin layer plates is described. The enzyme-substrate combination: pig liver esterase-indophenylacetate (chromogenic substrate) was the most sensitive. The following parameters concerning the sensitivity of the method were investigated: enzyme source, substrate, pH, inhibition time, inhibition temperature, thickness of the cellulose layer, stationary phase.

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Herrn o.Univ.-Prof. Dr. O. Hoffmann-Ostenhof, Vorstand des Instituts für Allgemeine Biochemie, Universität Wien, zum 60. Geburtstag gewidmet.

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Wir danken dem Fonds zur Förderung der wissenschaftlichen Forschung, der uns die Durchführung dieser Arbeit (Projekt Nr. 2161) ermöglichte.

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Ing. B. Rapié dankt der SEA-Stiftung (Scientific Exchange Agreement) für die Gewährung eines Stipendiums.     

An epidemic of scurvy in Afghanistan: assessment and response

In March 2002, there were reports of a hemorrhagic fever outbreak in western Afghanistan. It was later confirmed that the hemorrhagic symptoms and increased mortality were actually due to scurvy. Most aid workers did not include scurvy in the initial differential diagnosis because it is uncommon throughout the world and has mainly been reported in refugee populations in recent times. A rapid assessment confirmed the cases clinically, estimated a prevalence rate of 6.3% (a severe public health problem), and determined that the attack rates peaked each year in January and February (the end of the winter). Many Afghans have limited dietary diversity due to isolated locations, lengthy winters, the continuing drought of the last four years, asset depletion, and loss of livelihood. After numerous food and fortification options to prevent future outbreaks had been considered, vitamin C tablet supplementation was selected because of the relatively rapid response time as compared with other prevention methods. A three-month course of vitamin C tablets was distributed to 827 villages in at-risk areas. The tablets were acceptable and compliance was good. No cases of scurvy were reported for the winter of 2002-03. The case study from Afghanistan demonstrates that scurvy can occur in nonrefugee or nondisplaced populations; vitamin C supplementation can be an effective prevention strategy; there is an urgent need to develop field-friendly techniques to diagnose micronutrient-deficiency diseases; food-security tools should be used to assess and predict risks of nutritional deficiencies; and the humanitarian community should address prevention of scurvy in outbreak-prone areas.     

Peanut proteins as food supplements: A compositional study of selected Virginia and Spanish peanuts

Three peanut cultivars (Virginia, red-skinned, and white-skinned Spanish) were analyzed and compared as potential protein supplements for food uses. The seeds were solvent-extracted in the laboratory to yield defatted flours with 9–10% nitrogen contents. Protein isolates were prepared from the flours by subsequent extraction with dilute salt solutions buffered at pH 7.0. Various parameters were compared, such as total protein contents, soluble proteins, amino acid compositions of flours and protein isolates, free amino acids and free sugars of defatted flours, and certain trace minerals in flours and soluble proteins. The application of these results to the selection of certain types of peanuts for potential uses as protein supplements in food products is discussed. Presented in the Symposium, Oilseed Proteins, 66th Annual AOCS Meeting, Dallas, Texas, April 27–30, 1975.