Radiochemical and biological characteristics of 99mTc-UBI 29-41 for imaging of bacterial infections

A technetium-99m-labeled peptide derived from ubiquicidine, further referred to as 99mTc-UBI 29-41, targets bacterial and fungal infections, but not sterile inflammatory processes, in experimental animals. This paper reports on the radiochemical and biological features of this radioactive agent and the importance of the amino acid sequence of UBI 29-41 for imaging of infections.Radiochemical analyses of 99mTc-UBI 29-41 and a radiolabeled scrambled version of this peptide, i.e. 99mTc-Sc-UBI 29-41, revealed that both peptides were labeled rapidly (within 10 min) and effectively with little colloid formation (less than 5% of the total radioactivity) and very little free pertechnetate (or radioactive intermediates) in the preparations containing radiolabeled peptide. Furthermore, association of the peptides with bacteria could be competed with excess unlabeled peptide and this association proved to be temperature-dependent. Based on this in vitro data we concluded that labeling of peptides with 99mTc by this direct method is rapid, efficient, and safe.Scintigraphy demonstrated that radioactivity is rapidly removed from the circulation (half-lifes of UBI 29-41 and Sc-UBI 29-41 were 16 and 21 min, respectively) mainly by renal clearance. Analysis of murine blood revealed that only a small proportion of the intravenously injected 99mTc-peptides is associated with blood cells. Although both radiolabeled peptides accumulated rapidly at sites of infection, the values for 99mTc-UBI 29-41 were higher (P < 0.05) than for 99mTc-Sc-UBI 29-41. Moreover, injection of excess unlabeled UBI 29-41, but not Sc-UBI 29-41, into Staphylococcus aureus-infected mice prior to injection of 99mTc-UBI 29-41 significantly (P < 0.05) reduced the accumulation of this radiopharmaceutical at the site of infection. In addition, we observed significantly (P < 0.01) higher amounts of 99mTc-UBI 29-41 at the site of infection in mice using a carrier-free radiolabeled UBI 29-41 as compared with unpurified preparations containing radiolabeled UBI 29-41. This in vivo data indicates that the amino acid sequence of 99mTc-UBI 29-41 contributes to its accumulation at the site of infection.     

Panel 2.10: reproductive, mental, and child health

This is a summary of the presentations and discussion of Panel 2.10, Reproductive, Mental, and Child Health of the Conference, Health Aspects of the Tsunami Disaster in Asia, convened by the World Health Organization (WHO) in Phuket, Thailand, 04-06 May 2005. The topics discussed included issues related to reproductive, mental, and child health as pertain to the responses to the damage created by the Tsunami. It is presented in the following major sections: (1) background; (2) key issues; (3) discussion; and (4) recommendations. Key issues discussed included: (1) coordination/collaboration; (2) provision of services; and (3) raising awareness and advocacy.     

An optimized clarithromycin-free 14-day triple therapy for Helicobacter pylori eradication achieves high cure rates in Uruguay

Background

Strong acid inhibition increases cure rates with triple therapy and 14-day are more effective than 7-day treatments. The combination of amoxicillin plus metronidazole at full doses has been shown to overcome metronidazole resistance and to achieve good eradication rates even in patients harboring resistant strains. No previous studies have been reported in Latin-America with this optimized triple-therapy scheme.

IgA nephropathy presenting with renal failure and pulmonary hemorrhage

Pulmonary renal syndromes are unusual, but frequently life-threatening manifestations of a distinct group of disorders in the pediatric age group. Although IgA nephropathy is a common cause of hematuria, it is an extremely rare cause of pulmonary renal syndrome, causing high mortality, and has mostly been reported in adult patients. We describe the youngest patient with this presentation reported to date, a 14-year-old male, who presented with end stage renal disease and pulmonary hemorrhage and was found to have IgA nephropathy by renal biopsy and pulmonary capillaritis by open lung biopsy. His lung disease was successfully treated with immunosuppressive medications. Despite this being a rare manifestation of IgA nephropathy, clinicians need to be aware of this presentation as it is potentially fatal, but amenable to aggressive immunosuppression.     

Monoclonal antibodies against the Tn-specific isolectin B4 from Vicia villosa seeds: characterization of the epitope of the blocking antibody VV34

Vicia villosa isolectin B4 (VVLB4) recognizes the Tn antigen (GalNAc-O-Ser/Thr) exposed in certain human carcinomas. We have produced anti-VVLB4 monoclonal antibodies (MAbs), and their lectin recognition selectivity was assessed by ELISA and Western blot against the purified Gal/GalNAc-specific lectins from Vicia villosa, Salvia sclarea, Helix pomatia, Arachis hypogaea, Glycine max, and Dolichos biflorus. The antibodies were also tested for their ability to block the binding of VVLB4 to the Tn antigen expressed on immobilized asialo ovine submaxillary mucin. Two MAbs, VV34 and VV2, specifically recognized VVLB4 and impaired the binding of the lectin to the Tn antigen by 98% and 21%, respectively. On the other hand, MAbs VV1 and VV22 cross-reacted with other purified lectins. The four antibodies recognized native and periodate-oxidized nonreduced as well as reduced VVLB4 after SDS-PAGE and Western blot, suggesting that they were recognizing continuous polypeptide epitopes. The VV34 antibody recognized two tryptic peptides (7-29 and 96-106) from VVLB4, which are contiguous in the three-dimensional structure of the lectin. The minimum structural determinant of the epitope was mapped to the polypeptide stretch (18)LILQED(23) using a set of overlapping synthetic peptides. This region of the molecule encompasses the C-terminal part of the loop joining strands beta1 and beta2 and the N-terminal part of beta2, and is located about 20-25 A away from the center of the Tn-combining site.