ABSTRACT
El objetivo del presente trabajo fue desarrollar un péptido híbrido, que presente una secuencia capaz de quelatar al 99mTc y otra con afinidad por el receptor de la vitronectina, que permita la detección in vivo de tumores malignos. El marcaje del péptido PICIC3 con 99mTc se realizó de forma directa. Se estudió la estabilidad del complejo en exceso de L-cisteína y en plasma, la unión a proteínas plasmáticas, el coeficiente de partición en el sistema NaCl 0.9 por ciento:n-octanol, la carga del complejo mediante electroforesis y la afinidad por el receptor de la vitronectina se valoró a partir de un ensayo de saturación con membranas de células B16-F10. Se determinó la biodistribución en ratones C57BL/6 con injertos de melanoma B16-F10. Conclusiones: El péptido desarrollado mostró una afinidad satisfactoria por el receptor de la vitronectina y que permitió la detección in vivo de los melanomas múridos del tipo B16-F10 en los ratones injertados.
The aim of the present work was to develop a hybrid peptide, with a sequence for the chelation of 99mTc and other with affinity for the vitronectine receptor, to allow in vivo detection of malignant tumors. 99mTc-labeling of peptide PICIC3 was directly performed. The stability in presence of L-cysteine excess and plasma of the complex, its binding to plasma proteins, the partition coefficient in NaCl 0.9 percent:n-octanol, the charge of the chelate by electrophoresis and the peptide affinity for the vitronectine receptor by a saturation assay using membranes of B16-F10 cells, were studied. Biodistribution in C57BL/6 mice injerted with melanoma B16-F10 was assessed. Conclusions: Developed peptide showed a satisfactory affinity for the vitronectine receptor and allowed in vivo detection of murine melanomas in mice with allografts.
Subject(s)
Animals , Mice , /metabolism , Melanoma, Experimental , Melanoma, Experimental/metabolism , Peptides, Cyclic/pharmacokinetics , Technetium/pharmacokinetics , Tissue Distribution , Drug Stability , Time Factors , Isotope Labeling/methods , Peptides, Cyclic/metabolism , Technetium/metabolismABSTRACT
The pathophysiology of inflammatory bowel disease (IBD) involves the production of diverse lipid mediators, namely eicosanoid, lysophospholipids, and platelet-activating factor, in which phospholipase A2 (PLA2) is the key enzyme. Thus, it has been postulated that control of lipid mediators production by inhibition of PLA2 would be useful for the treatment of IBD. This hypothesis has been tested in the present study by examining the therapeutic effect of a novel natural probitic Bacillus subtilis PB6 (ATCC- PTA 6737). B. subtilis PB6 is found to secrete surfactins (cyclic lipopeptides) which have anti-bacterial potential. These surfactins inhibit PLA2, a rate-limiting enzyme involved in the arachidonic acid associated inflammatory pathway and could downregulate the inflammatory response by regulating the eicosanoid and cytokine pathways. With this concept, an experimental animal trial has been conducted in a rat model of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. The oral administration of PB6 suppresses the colitis as measured by mortality rate, changes in the weight gain, colon morphology and the levels of plasma cytokines. The animals treated orally with PB6 at 1.5 x 10(8) CFU/kg thrice daily from day 4 to 10 significantly improve gross pathology of the colon and regain the colon weight to normal (p < 0.05), compared to TNBS-induced positive control. The plasma levels of pro-inflammatory cytokines (TNF-alpha, 1L-1beta, IL-6 and IFN-gamma) are also significantly lowered (p < 0.05) and anti-inflammatory cytokine (IL-I0 and TGF-beta) significantly (p < 0.05) increased after the oral administration of PB6 on day 11. The present study supports the concept that PB6 inhibits PLA2 by the secreting surfactins. In a clinical investigation, it is found to be well tolerated by all the healthy volunteers.
Subject(s)
Animals , Bacillus subtilis , Bacterial Proteins/metabolism , Body Weight , Colitis, Ulcerative/blood , Colitis, Ulcerative/chemically induced , /microbiology , Colitis, Ulcerative/therapy , Colon/immunology , Colon/microbiology , Colon/pathology , Cytokines/blood , Disease Models, Animal , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Lipopeptides/metabolism , Male , Organ Size , Peptides, Cyclic/metabolism , Phospholipases A2/metabolism , Probiotics , Random Allocation , Rats , Rats, Wistar , Trinitrobenzenesulfonic AcidABSTRACT
Hemoglobin is known to support the growth of several bacterial species. The growth and the production of siderophores by 4 strains of mycobacteria in the presence of hemoglobin was studied in vitro. The findings were compared with those obtained in the presence of equivalent concentrations of iron in the medium. Increase in the concentrations of hemoglobin caused an appreciable increase in the growth of all 4 strains. This was however, accompanied by a significant decrease in the production of both exochelins and mycobactins. It was also observed that hemoglobin supported the growth of all strains as well as that with free iron and the concentrations of both siderophores was significantly higher in the presence of hemoglobin than in that of free iron.