Intranasal vaccination with poly(lactide-co-glycolide) microparticles containing a peptide T of Ole e 1 prevents mice against sensitization.

BACKGROUND: Biodegradable microparticles, in particular poly(lactide-co-glycolide) (PLGA), have been shown as potential delivery vehicles for intranasal (i.n.) vaccines in animal models. OBJECTIVES: To evaluate whether i.n. administration of PLGA microparticles containing a peptide with the major T cell epitope of Ole e 1, the main allergen of olive pollen, prevented mice from allergic sensitization to the whole protein. METHODS: Peptide-PLGA microparticles were prepared by a solvent evaporation double emulsion method. Microparticles in a size range of 0.8 mum were evaluated for peptide loading and in vitro antigen release. Stability and immunogenicity of the entrapped peptide were retained, as determined by dot blot and ELISA inhibition. BALB/c mice were intranasally treated with peptide-PLGA microparticles for 3 consecutive days, 1 week before sensitization/challenge to Ole e 1. Blood, lungs and spleen were collected and analysed for immune response. Biodistribution of microparticles was investigated using confocal microscopy. RESULTS: I.n. pretreatment of BALB/c mice with peptide-PLGA microparticles before sensitization to Ole e 1 led to a significant inhibition of serum allergen-specific IgE and IgG1 antibody levels, but a marked increase of specific IgG2a antibodies as compared with sham-pretreated mice. Moreover, IL-5 and IL-10 levels in spleen cell cultures were suppressed in peptide-PLGA pretreated mice. The airway histopathologic parameters associated with inflammation were significantly suppressed by the pretreatment. CONCLUSION: These results demonstrate that i.n. immunization with peptide T-PLGA microparticles is effective in preventing subsequent allergic sensitization to Ole e 1. Our data indicate that peptide-PLGA microparticles may be promising candidates for the design of nasal vaccines against allergic diseases in humans.

Sympathetic sprouting in dorsal root ganglia (DRG): a recent histological finding?

During the nineties it was described, as an original finding, the existence of afferent amyelinic nerve endings in animal dorsal root ganglia (DRG) caused by diverse experimental lesions. These works do not take into account the historical studies carried out by Ehrlich (1886), Ramón y Cajal (1890) and Dogiel (1885) among others. Ramón y Cajal (1899) confirmed the existence of these nerve endings naming them after their discoverer as "Dogiel's arborisations". Ramón y Cajal claims that these endings originate from fibres of sympathetic nature, something supported by later authors devoted to this topic. In any case, the same authors remarked already a possible relationship with pathological phenomena, nonetheless always referring to the frequent occasions in which the same images appeared in healthy animals. In this work we review the bibliography about the classically named "Terminal Dogiel's nests" which in modern literature have been referred to as sprouting of sympathetic axons in dorsal root ganglia likely related with sympathetically maintained pain. Furthermore, we present the finding, not described up to date, of multiple afferent amyelinic nervous endings related with the "Terminal Dogiel's nests" observed in different DRG from young adult healthy rabbits.

Supplementation of University of Wisconsin solution with Nitroglycerin and Nicorandil in long-term myocardial preservation: effects on the oxidative state, endothelial function and morphology.

The purpose of this study was to assess the effects of the addition of Nitroglycerin or Nicorandil to University of Wisconsin solution in long-term myocardial preservation. In a model of heterotopic heart transplantation in pigs, the donor heart was preserved for 24 hours by means of continuous perfusion in this solution, in the presence or absence of these drugs. During this period, the oxygenation and pH of the solution were measured, as were lactate concentrations and enzyme release. At regular intervals following reperfusion we measured the concentrations of enzymes, antioxidants, glutathione peroxidase, glutathione reductase, malondialdehyde, endothelin and nitrite, and, two hours later, samples of both ventricles were taken for a morphological study. In the treated groups there was a higher lactate production during preservation and, during reperfusion, the signs of contracture and the elevation of enzyme levels were more marked than in the untreated groups. In contrast, the glutathione reductase concentrations did not decrease during the first phase of reperfusion and were directly correlated with those of antioxidants, endothelin levels increased less than in the untreated groups and, in the case of nitroglycerin, the nitrite concentration was significantly greater than in the remaining groups. We conclude that nitroglycerin and nicorandil improved the oxidative state and endothelial function and did not produce substantial morphological changes, but increased cell necrosis and contracture, possibly due to the duration of ischemia.