Respiratory and Systemic Effects of LASSBio596 Plus Surfactant in Experimental Acute Respiratory Distress Syndrome.

BACKGROUND/AIMS: Exogenous surfactant has been proposed as adjunctive therapy for acute respiratory distress syndrome (ARDS), but it is inactivated by different factors present in the alveolar space. We hypothesized that co-administration of LASSBio596, a molecule with significant anti-inflammatory properties, and exogenous surfactant could reduce lung inflammation, thus enabling the surfactant to reduce edema and improve lung function, in experimental ARDS. METHODS: ARDS was induced by cecal ligation and puncture surgery in BALB/c mice. A sham-operated group was used as control (CTRL). After surgery (6 hours), CTRL and ARDS animals were assigned to receive: (1) sterile saline solution; (2) LASSBio596; (3) exogenous surfactant or (4) LASSBio596 plus exogenous surfactant (n = 22/group). RESULTS: Regardless of exogenous surfactant administration, LASSBio596 improved survival rate and reduced collagen fiber content, total number of cells and neutrophils in PLF and blood, cell apoptosis, protein content in BALF, and urea and creatinine levels. LASSBio596 plus surfactant yielded all of the aforementioned beneficial effects, as well as increased BALF lipid content and reduced surface tension. CONCLUSION: LASSBio596 exhibited major anti-inflammatory and anti-fibrogenic effects in experimental sepsis-induced ARDS. Its association with surfactant may provide further advantages, potentially by reducing surface tension.

Vascular endothelial growth factor-like and its receptor in a crustacean optic ganglia: a role in neuronal differentiation?

The neural system appears before the vascular system in the phylogenetic tree. During evolution, vascular system generation takes advantage of the pre-existing vascular endothelial growth factor (VEGF) in order to form its networks. Nevertheless, the role of VEGF in neuronal and glial cells is not yet completely understood. In order to support the hypothesis of a neural role for VEGF, we searched for VEGF- and VEGF receptor (VEGFR)-like immunoreactivities (immunohisto/cytochemistry and Western blotting) in the eyestalk of the invertebrate Ucides cordatus (Crustacea, Brachyura, Ucididae). Our results showed that both neurons and glial cells expressed VEGF-immunoreactivity, and that VEGFR was evidenced in neural cells. This is the first report about the VEGF/VEGFR-like immunoreactivities in the nervous tissue of a crustacean, and enables U. cordatus to be included in the repertoire of animal models used for ascertaining the role of VEGF in the nervous system.

Differential immunodetection of L-DOPA decarboxylase and tyrosine hydroxylase in the vertebrate retina.

The immunocytochemical staining of L-DOPA decarboxylase (DDC) and tyrosine hydroxylase (TH) in cells of the developing avian retina and in cells of the retina of adult rats and opossum were compared. DDC was identified at embryonic day 8 in the chick, in cells in the inner nuclear layer (INL). At embryonic day 13, two types of DDC positive cells were observed; type 1, with the soma located in the innermost layer of the INL; and type 2, with the soma located two cell rows from the innermost part of the INL. Immunolabeling for DDC in the presumptive outer plexiform layer was more clearly defined at embryonic day 19 and at post-hatched day 7. Processes of DDC labeled cells extended into the inner plexiform layer, supporting the amacrine identity of these cells. Dot-blot analysis revealed that DDC could be detected at embryonic day 4. Confocal microscopy showed that at embryonic day 10, DDC positive cells, but not TH positive cells, were found. After embryonic day 13, cells immunolabeled for DDC and DDC plus TH were detected. The mean density of DDC positive cells quantified in whole-mounted chick retinas showed that in all stages the density of DDC positive cells exceeded that of TH positive cells by 10-13-fold. As for the avian retina, density of DDC positive cells in opossum and rat retinas exceeded the density of TH positive cells. In opossum, Müller fibers were also clearly labeled for DDC but not for TH. We propose the hypothesis that the dopamine synthesis in the developing avian retina as well as in the mature rat and opossum tissue is greater than would be expected from TH staining alone.