The mouse anterior chamber angle and trabecular meshwork develop without cell death

BACKGROUND: The iridocorneal angle forms in the mammalian eye from undifferentiated mesenchyme between the root of the iris and cornea. A major component is the trabecular meshwork, consisting of extracellular matrix organized into a network of beams, covered in trabecular endothelial cells. Between the beams, channels lead to Schlemm's canal for the drainage of aqueous humor from the eye into the blood stream. Abnormal development of the iridocorneal angle that interferes with ocular fluid drainage can lead to glaucoma in humans. Little is known about the precise mechanisms underlying angle development. There are two main hypotheses. The first proposes that morphogenesis involves mainly cell differentiation, matrix deposition and assembly of the originally continuous mesenchymal mass into beams, channels and Schlemm's canal. The second, based primarily on rat studies, proposes that cell death and macrophages play an important role in forming channels and beams. Mice provide a potentially useful model to understand the origin and development of angle structures and how defective development leads to glaucoma. Few studies have assessed the normal structure and development of the mouse angle. We used light and electron microscopy and a cell death assay to define the sequence of events underlying formation of the angle structures in mice. RESULTS: The mouse angle structures and developmental sequence are similar to those in humans. Cell death was not detectable during the period of trabecular channel and beam formation. CONCLUSIONS: These results support morphogenic mechanisms involving organization of cellular and extracellular matrix components without cell death or atrophy

Avaliação sensorial de cebolinha (Allium cepa, L.) orgânica para conserva.

bitstream/CPACT-2009-09/11943/1/documento_233.pd

Prognostic stratification improvement by integrating ID1/ID3/IGJ gene expression signature and immunophenotypic profile in adult patients with B-ALL

Characteristics of pronostic groups according to EuroFlow immunophenotype. (TIFF 1364 kb

Haploinsufficient Bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressure

BACKGROUND: Glaucoma is a blinding disease usually associated with high intraocular pressure (IOP). In some families, abnormal anterior segment development contributes to glaucoma. The genes causing anterior segment dysgenesis and glaucoma in most of these families are not identified and the affected developmental processes are poorly understood. Bone morphogenetic proteins (BMPs) participate in various developmental processes. We tested the importance of Bmp4 gene dosage for ocular development and developmental glaucoma. RESULTS: Bmp4(+/-) mice have anterior segment abnormalities including malformed, absent or blocked trabecular meshwork and Schlemm's canal drainage structures. Mice with severe drainage structure abnormalities, over 80% or more of their angle's extent, have elevated IOP. The penetrance and severity of abnormalities is strongly influenced by genetic background, being most severe on the C57BL/6J background and absent on some other backgrounds. On the C57BL/6J background there is also persistence of the hyaloid vasculature, diminished numbers of inner retinal cells, and absence of the optic nerve. CONCLUSIONS: We demonstrate that heterozygous deficiency of BMP4 results in anterior segment dysgenesis and elevated IOP. The abnormalities are similar to those in human patients with developmental glaucoma. Thus, BMP4 is a strong candidate to contribute to Axenfeld-Rieger anomaly and other developmental conditions associated with human glaucoma. BMP4 also participates in posterior segment development and wild-type levels are usually critical for optic nerve development on the C57BL/6J background. Bmp4(+/-) mice are useful for studying various components of ocular development, and may allow identification of strain specific modifiers affecting a variety of ocular phenotypes

High expression of ID family and IGJ genes signature as predictor of low induction treatment response and worst survival in adult Hispanic patients with B-acute lymphoblastic leukemia

Table S4. Complete list of signaling pathways dysregulated in patients who achieved complete remission therapy. Signaling pathway analysis was done using MetaCore KPA using the set of 442 genes differentially expressed between good and poor response group. (XLSX 10 kb

Oral administration of paclitaxel with pegylated poly(anhydride) nanoparticles: permeability and pharmacokinetic study

The aim of this work was to study the potential of pegylated poly(anhydride) nanoparticles as carriers for the oral delivery of paclitaxel (PTX). Paclitaxel is an anticancer drug, ascribed to the class IV of the Biopharmaceutical Classification system, characterised for its low aqueous solubility and to act as a substrate of the P-glycoprotein and cytochrome P450. For the pegylation of nanoparticles, three different poly(ethylene glycol) (PEG) were used: PEG 2000 (PTX-NP2), PEG 6000 (PTX-NP6) and PEG 10,000 (PTX-NP10). The transport and permeability of paclitaxel through the jejunum mucosa of rats was determined in Ussing chambers, whereas its oral bioavailability was studied in rats. The loading of PTX in pegylated nanoparticles increased between 3 and 7 times the intestinal permeability of paclitaxel through the jejunum compared with the commercial formulation Taxol. Interestingly, the permeability of PTX was significantly higher for PTX-NP2 and PTX-NP6 than for PTX-NP10. In the in vivo studies, similar results were obtained. When PTX-NP2 and PTX-NP6 were administered to rats by the oral route, sustained and therapeutic plasma levels of paclitaxel for at least 48 h were observed. The relative oral bioavailability of paclitaxel delivered in nanoparticles was calculated to be 70% for PTX-NP2, 40% for PTX-NP6 and 16% in case of PTX-NP10. All of these observations would be related with both the bioadhesive properties of these carriers and the inhibitory effect of PEG on the activity of both P-gp and P450 cytochrome

Nanoparticules muco-pénétrantes: véhicules pour l’administration orale du paclitaxel

Paclitaxel is an anticancer drug used as solution for perfusion for the treatment of certain types of cancers. In the last years, a number of strategies have been proposed for the development of an oral formulation of this drug. However, this task is quite complicated due to the poor aqueous solubility of paclitaxel as well as the fact that this compound is substrate of the intestinal P-glycoprotein and the cytochrome P450 enzymatic complex. In this work, we have developed pegylated nanoparticles with mucopenetrating properties in order to conduct paclitaxel onto the surface of the enterocyte. These nanoparticles displayed a size of about 180 nm and a drug loading close to 15% by weight. The pharmacokinetic study in mice has shown that these nanoparticles were capable to offer therapeutic plasma levels of paclitaxel up to 72 hours. In addition, the oral relative bioavailability of paclitaxel when loaded in nanoparticles pegylated with poly(ethylene glycol) 2000 (PEG) was found to be 85%. In a subcutaneous model of tumour in mice, these pegylated nanoparticles administered orally every 3 days have demonstrated a similar efficacy than Taxol® administered intravenously every day during 9 days. All of these results suggested that these pegylated nanoparticles were capable to cross the mucus layer of the gut and, then, reach the surface of the enterocytes. The PEG molecules would facilitate the adhesion of nanoparticles to this epithelial surface, minimise the pre-systemic metabolism of paclitaxel and, thus, promote its absorption

Relationship of runoff, erosion and sediment yield to weather types in the Iberian Peninsula

Precipitation has been recognized as one of the main factors driving soil erosion and sediment yield (SY), and its spatial and temporal variability is recognized as one of themain reasons for spatial and temporal analyses of soil erosion variability. The weather types (WTs) approach classifies the continuumof atmospheric circulation into a small number of categories or types and has been proven a good indicator of the spatial and temporal variability of precipitation. Thus, themain objective of this study is to analyze the relationship betweenWTs, runoff, soil erosion (measured in plots), and sediment yield (measured in catchments) in different areas of the Iberian Peninsula (IP) with the aimof detecting spatial variations in these relationships. To this end, hydrological and sediment information covering the IP from several Spanish research teams has been combined, and related with daily WTs estimated by using the NMC/NCAR 40-Year Reanalysis Project. The results showthat, in general, a fewWTs (particularly westerly, southwesterly and cyclonic) provide the largest amounts of precipitation; and southwesterly, northwesterly and westerly WTs play an important role in runoff generation, erosion and sediment yield as they coincide with the wettest WTs. However, this study highlights the spatial variability of erosion and sediment yield in the IP according to WT, differentiating (1) areas under the influence of north and/or north-westerly flows (the north coast of Cantabria and inland central areas), (2) areas under the influence of westerly, southwesterly and cyclonic WTs (western and southwestern IP), (3) areas in which erosion and sediment yield are controlled by easterly flows (Mediterranean coastland), and (4) lastly, a transitional zone in the inland northeast Ebro catchment,wherewe detected a high variability in the effects ofWTs on erosion. Overall results suggest that the use of WTs derived fromobserved atmospheric pressure patterns could be a useful tool for inclusion in future projections of the spatial variability of erosion and sediment yield, as models capture pressure fields reliably