The population incidence of culture-confirmed invasive bacterial infection was 28/100 000. One-third of infections were hospital acquired and, of the community-acquired infections, two-thirds occurred in children with pre-existing co-morbidities. In previously healthy children, therefore, the incidence of community-acquired invasive bacterial infection was only

6.4/100 000. Conclusions Although infection was suspected in almost half the children admitted to hospital, a significant pathogen was cultured from blood or CSF in only 2.4%, mainly among children with pre-existing co-morbidities, who may require a more broad-spectrum empiric antibiotic regime compared Pexidartinib to previously healthy children. Invasive bacterial infection in previously healthy children is now very rare. Improved strategies to manage low-risk febrile children are required.”
“To develop a more potent thrombolytic agent, four Sak (staphylokinase) variants were constructed, in which RGD (Arg-Gly-Asp) sequences are GSK1838705A cost introduced into diferent sites of the N-terminus of Sak. These

variants were successfully expressed in Escherichia coli DHS alpha as soluble cytoplasmic proteins in a 5-litre fermentor and accounted for more than 40% of the total cellular protein. The expressed proteins were subsequently purified, employing a similar three-step chromatographic purification process. SDS/PAGE and HPLC-MS analyses indicated that the purified proteins were almost completely homogeneous, the purity of the variants exceeding 95%. Further investigations into the properties of the Sak variants showed that mutations at the N-terminus significantly affected N-terminal methionine excision, and serine residues at the N-terminus of Sak appeared to play an important role in the process. Kinetic analysis of r-Sak (recombinant Sak) and its variants using plasminogen as substrate indicated that the mutations affected the proteolysis. In addition, a significant inhibitory effect of PR171 the Sak variants at 2.0 mu M was observed on the ADP-induced aggregation of platelets compared with that of r-Sak, whether N-terminally cleaved or not (P < 0.05). Furthermore, the inhibitory activity of Sak variants after N-terminal proteolysis

was higher than that of native Sak variants.”
“The cutaneous leucocyte-associated antigen receptor (CLA) can direct Leishmania-specific T lymphocytes towards inflamed skin lesions. Homing receptors [CLA, lymphocyte-associated antigen 1 (LFA-1) or CD62L] were analysed in lymphocytes from blood and cutaneous leishmaniasis (CL) lesions. CL patients with active lesions (A-CL) presented lower levels of T lymphocytes expressing the CLA(+) phenotype (T CD4(+) = 10.4% +/- 7.5% and T CD8(+) = 5.8% +/- 3.4%) than did healthy subjects (HS) (T CD4(+) = 19.3% +/- 13.1% and T CD8(+) = 21.6% +/- 8.8%), notably in T CD8(+) (P < 0.001). In clinically cured patients these percentages returned to levels observed in HS. Leishmanial antigens up-regulated CLA in T cells (CLA(+) in T CD4(+) = 33.