RESUMEN
Heparan sulfate (HS), a glycosaminoglycan related to heparin, is a linear polysaccharide, consisting of repeating disaccharide units. This compound is involved in multiple biological processes such as inflammation, coagulation, angiogenesis and viral infections. Our work focuses on the synthesis of simple HS analogs for the study of structure-activity relationships, with the aim of modulating these biological activities. Thioglycoside analogs, in which the interglycosidic oxygen is replaced by a sulfur atom, are very interesting compounds in terms of therapeutic applications. Indeed, the thioglycosidic bond leads to an improvement of their stability and can allow the inhibition of enzymes involved in physiological and pathological processes. In our previous work, we developed a synthetic sequence which led to a non-sulfated thiodisaccharide analog of HS. In this paper, we report our results of the development of a new synthetic method allowing access to the novel sulfated S-disaccharide, as well as to their oxygenated analogues (O-disaccharide and sulfated O-disaccharide). These 4 compounds were also tested for the inhibition of heparanase, an enzyme involved in biological processes like tumor growth and inflammation. The obtained IC50 values in the micromolar range showed the impact of the interglycosidic sulfur atom and the 6-sulfate group.
Asunto(s)
Disacáridos , Heparitina Sulfato , Disacáridos/química , Disacáridos/farmacología , Glucuronidasa , Heparitina Sulfato/química , Heparitina Sulfato/farmacología , Humanos , Inflamación , AzufreRESUMEN
Bact-Alert automatized system for blood cultures: 5 vs 7 days of incubation. First Argentine multicentre study. Between January and December 2001, we analyzed 80,141 blood cultures by the Bact-Alert system (14,960 FAN aerobics, 3,855 FAN anaerobic, 11,114 standards aerobics, 11,367 standards anaerobic, 12,054 pediatrics and 26,791 FAN pediatrics bottles) and 44.235 series from 27.615 patients at eight hospitals of Buenos Aires city, one of La Plata city and three of the Buenos Aires province. A total of 13,657 blood cultures yielded a positive result. Only 181 of them had been detected as positive between the 5th and 7th day of incubation and only 26 (0.19%) had clinical significance (Staphylococcus aureus 3; coagulase negative staphylococci 2; Enterococcus faecalis 1; Streptococcus pneumoniae 2; Campylobacter spp 1; Escherichia coli 1; Enterobacter cloacae 1; Enterobacteraerogenes 1; Citrobacter freundii 1; Klebsiella pneumoniae 1; Proteus mirabilis 1; Serratia marcescens 4; yeasts 7, including one strain of Cryptococcus neoformans). Of the total of contaminants, 38% were isolated by the anaerobic standard (65% were Propionibacterium spp and 29% coagulase negative staphylococci), 31.2% by the FAN aerobic (33.3% difphteroids and 28.9% Bacillus spp), 11.8% by the pediatric, 9% by FAN pediatric, 8.33% by aerobic standard and 1.4% by FAN anaerobic bottle. Our results show that the prolonged incubation of blood cultures for more than 5 days using the Bact-Alert system is unnecessary.
Asunto(s)
Bacteriemia/microbiología , Bacterias Aerobias/aislamiento & purificación , Bacterias Anaerobias/aislamiento & purificación , Técnicas Bacteriológicas , Sangre/microbiología , Argentina/epidemiología , Automatización , Bacteriemia/epidemiología , Bacterias Aerobias/crecimiento & desarrollo , Bacterias Anaerobias/crecimiento & desarrollo , Humanos , Laboratorios de Hospital/estadística & datos numéricos , Factores de TiempoRESUMEN
Bact-Alert automatized system for blood cultures: 5 vs 7 days of incubation. First Argentine multicentre study. Between January and December 2001, we analyzed 80,141 blood cultures by the Bact-Alert system (14,960 FAN aerobics, 3,855 FAN anaerobic, 11,114 standards aerobics, 11,367 standards anaerobic, 12,054 pediatrics and 26,791 FAN pediatrics bottles) and 44.235 series from 27.615 patients at eight hospitals of Buenos Aires city, one of La Plata city and three of the Buenos Aires province. A total of 13,657 blood cultures yielded a positive result. Only 181 of them had been detected as positive between the 5th and 7th day of incubation and only 26 (0.19
) had clinical significance (Staphylococcus aureus 3; coagulase negative staphylococci 2; Enterococcus faecalis 1; Streptococcus pneumoniae 2; Campylobacter spp 1; Escherichia coli 1; Enterobacter cloacae 1; Enterobacteraerogenes 1; Citrobacter freundii 1; Klebsiella pneumoniae 1; Proteus mirabilis 1; Serratia marcescens 4; yeasts 7, including one strain of Cryptococcus neoformans). Of the total of contaminants, 38
were isolated by the anaerobic standard (65
were Propionibacterium spp and 29
by the FAN aerobic (33.3
difphteroids and 28.9
by the pediatric, 9
by aerobic standard and 1.4
by FAN anaerobic bottle. Our results show that the prolonged incubation of blood cultures for more than 5 days using the Bact-Alert system is unnecessary.
RESUMEN
Bact-Alert automatized system for blood cultures: 5 vs 7 days of incubation. First Argentine multicentre study. Between January and December 2001, we analyzed 80,141 blood cultures by the Bact-Alert system (14,960 FAN aerobics, 3,855 FAN anaerobic, 11,114 standards aerobics, 11,367 standards anaerobic, 12,054 pediatrics and 26,791 FAN pediatrics bottles) and 44.235 series from 27.615 patients at eight hospitals of Buenos Aires city, one of La Plata city and three of the Buenos Aires province. A total of 13,657 blood cultures yielded a positive result. Only 181 of them had been detected as positive between the 5th and 7th day of incubation and only 26 (0.19
) had clinical significance (Staphylococcus aureus 3; coagulase negative staphylococci 2; Enterococcus faecalis 1; Streptococcus pneumoniae 2; Campylobacter spp 1; Escherichia coli 1; Enterobacter cloacae 1; Enterobacteraerogenes 1; Citrobacter freundii 1; Klebsiella pneumoniae 1; Proteus mirabilis 1; Serratia marcescens 4; yeasts 7, including one strain of Cryptococcus neoformans). Of the total of contaminants, 38
were isolated by the anaerobic standard (65
were Propionibacterium spp and 29
coagulase negative staphylococci), 31.2
by the FAN aerobic (33.3
difphteroids and 28.9
Bacillus spp), 11.8
by the pediatric, 9
by FAN pediatric, 8.33
by aerobic standard and 1.4
by FAN anaerobic bottle. Our results show that the prolonged incubation of blood cultures for more than 5 days using the Bact-Alert system is unnecessary.
RESUMEN
The excitonic luminescence of a highly ordered single conjugated polymer chain is studied by microphotoluminescence. At T< or =10 K it consists of a single Lorentzian line. The linewidth increases linearly with T between 6 and 60 K, from 350 microeV at 6 K, indicating a pure dephasing time of approximately 2 ps. Above 10 K, other neighboring regions along the chain direction start to emit at a slightly higher (by approximately 1 meV) energy. This indicates very small inhomogeneous broadening, very long chains ( > or =10 microm), and a long range and very rapid exciton energy transfer ( >10 microm in <100 ps).
RESUMEN
It has been suggested that the FGF-2 binding site on heparan sulfate chains is a trisulfated pentasaccharide containing three hexuronic acid units. The configuration at C-5 of two of them being undetermined, we have synthesized the four possible pentasaccharides, and have evaluated their FGF-2 binding affinity through in vitro biological assays. The pentasaccharide containing L-iduronic acid as the sole hexuronic acid showed higher affinity for FGF-2 than the other pentasaccharides, where one hexuronic acid unit at least is D-glucuronic acid.
Asunto(s)
Factor 2 de Crecimiento de Fibroblastos/metabolismo , Ácido Glucurónico/química , Heparitina Sulfato/metabolismo , Ácido Idurónico/química , Aorta/citología , Aorta/efectos de los fármacos , Aorta/metabolismo , Sitios de Unión , Secuencia de Carbohidratos , División Celular/efectos de los fármacos , Células Cultivadas , Factor 2 de Crecimiento de Fibroblastos/farmacología , Heparitina Sulfato/síntesis química , Heparitina Sulfato/química , Humanos , Isomerismo , Datos de Secuencia Molecular , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Oligosacáridos/síntesis química , Oligosacáridos/químicaRESUMEN
Two high sulphated heparin-like polysaccharides (L1, MW 16,000 and L2, MW 11,700) were isolated from rat liver tissues, after DEAE-cellulose chromatography. Heparan sulphates from heart and lung tissues were isolated for comparison and fractionated according to their molecular weight. The anticoagulant activities in vitro were studied using clotting antifactor Xa, antifactor IIa, and APTT assay methods, falling in a narrow range (5-44 IU/mg) although the wide variability in molecular weight and sulphate content. The heparan sulphate nature of fractions L1 and L2 (sulphate/disaccharide ratio 2.05 and 2.48, respectively) has been verified by: a) low iduronic/glucuronic acid ratio; b) nitrous acid degradation followed by gel chromatography; c) heparinase treatment followed by gel chromatography; d) electrophoretic behaviour. Native proteoglycans have been isolated and the glycosidic chains compared with L1 and L2. Their anticoagulant activities in vitro and the fact that anti-Xa clotting activity was not neutralized by protamine sulphate are in accordance with the results of structural studies.