A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Evaluation of Atmospheric and Vacuum Residues Using Molecular Distillation and Optimization

The term atmospheric residue describes the material at the bottom of the atmospheric distillation tower having a lower boiling point limit of about 340°C; the term vacuum residue (heavy petroleum fractions) refers to the bottom of the vacuum distillation, which has an atmospheric equivalent boiling point (AEBP) above 540°C. In this work, the objective is to evaluate the behavior of different kinds of Brazilian atmospheric and vacuum residues using molecular distillation. The Falling Film Molecular Distillator was used. For the results obtained through this process, a significant range of temperature can be explored avoiding the thermal decomposition of the material. So these results are very important to the refinery decisions and improvements. The Experimental Factorial Design results showed that the temperature has more influence on the process than the feed flow rate, when a higher percentage of distillate is required.     

COPD: using nutrition to prevent respiratory function decline

Close to three-fourths of patients with chronic obstructive pulmonary disease (COPD) suffer from weight loss. Identifying a single cause for this is difficult, as several factors-including chronic mouth breathing, dyspnea, aerophagia, certain medications, and depression-often act in concert. Malnutrition can exacerbate symptoms of COPD by decreasing ventilatory muscle strength, exercise tolerance, and immunocompetence, and by increasing the risk of depression and anxiety. Goals of nutrition intervention are to prevent or reverse malnutrition without worsening the disease process and to improve respiratory function, thereby reducing morbidity and delaying mortality. Recommendations for intake of fats, carbohydrates, protein, and water must be individualized.     

Stabilisation of protein and oil in fish silage for use as a ruminant feed supplement

Fish silage was prepared from 96.5% offal obtained from Atlantic cod fillet processing and 3.5% (by wt) formic acid. The fish silage became an homogeneous liquid of low viscosity in 36–58 h at 20°C; however, the oil and protein components continued to be hydrolysed for several months. Addition of formaldehyde to fish silage (0.25 or 0.39% by wt) after liquefaction was complete, served to prevent continued protein hydrolysis and oxidative rancidity of the oil. It also decreased the development of ‘off-odours’, and the formation of total volatile bases. Fish silage was readily absorbed by hay at a ratio of 1.5 parts silage to 1.0 parts hay by weight; the product is referred to as ‘haylage’. Voluntary intake by wethers of ‘haylage’ prepared from de-oiled, formaldehyde-treated fish silage was better than for ‘haylage’ prepared from untreated fish silage. The crude protein content of ‘haylage’ rations was more than satisfactory for fattening lambs, although the energy content of ‘haylage’ rations may be a limiting factor. Retention of fish oil in the silage to increase the energy content of rations was unsuccessful because voluntary feed intake was depressed. The addition of formaldehyde to fish silage is advantageous when the product is to be fed to ruminant livestock since protein and lipid degradation in the feed, and also possibly in the rumen, are minimised and voluntary intake of ‘haylage’ by sheep is increased.     

Phosphorus Inputs to Lake Simcoe from 1990 to 2003: Declines in Tributary Loads and Observations on Lake Water Quality

Total phosphorus (TP) inputs to Lake Simcoe have led to hypolimnetic dissolved oxygen (DO) depletion and loss of cold water fish habitat. Since 1990, efforts have been made to reduce the total TP input to the lake below a defined target of 75 t/year, which was predicted to lead to reductions in spring TP concentration and improvements in end-of-summer hypolimnetic DO concentrations. The total TP load to the lake during the most recent period of record (1998/99-2003/04) ranged from 53 to 76 t/yr and averaged 67 t/yr, compared to an average of 114 t/yr estimated between 1990/91 and 1997/98 (range 85-157 t/yr). Reductions in TP loads from the catchment via tributary discharge (∼26 t) accounted for the majority of the decrease in total load between the two time periods. Total P concentrations decreased significantly in four out of six long-term monitored tributaries; however, concentrations in all six tributaries remain above the level recommended to avoid nuisance plant growth (30 μg/L). Although TP loads to the lake are currently below the target 75 t/yr, excessive growths of filamentous algae and macrophytes continue to be a problem in the nearshore zone. End-of-summer minimum hypolimnetic DO concentrations (average 4.3 mg/L, 1998/99-2003/04) remain substantially below the level (7 mg/L) that is considered protective of lake trout. Efforts to reduce TP loads to the lake therefore need to continue.     

Alagille syndrome: family studies

Alagille syndrome (AGS) is one of the major forms of chronic liver disease in childhood with severe morbidity and a mortality of 10 to 20%. It is characterised by cholestasis of variable severity with paucity of interlobular bile ducts and anomalies of the cardiovascular system, skeleton, eyes, and face. Previous studies suggest a wide variation in the expression of the disease and a high incidence of new mutations. To determine more accurately the rate of new mutations and to develop criteria for detecting the disorder in parents we systematically investigated parents in 14 families with an affected child. Clinical examination was supplemented by liver function tests, echocardiography, radiographic examination of the spine and forearm, ophthalmological assessment, and chromosome analysis. Six parents had typical anomalies in two or more systems pointing to the presence of autosomal dominant inheritance. Systematic screening of parents for the features defined in this study should improve the accuracy of genetic counselling.