Use of intravitreal bevacizumab in a patient with a Von Hippel-Lindau-associated retinal haemangioblastoma of the optic nerve head: a case report

<p>Abstract</p> <p>Introduction</p> <p>The optimum management of a capillary haemangioblastoma affecting the optic nerve head is not clear. A number of treatment modalities have been used to treat the tumours and their consequences. Ocular haemangioblastomas express high levels of vascular endothelial growth factor and levels have been correlated with tumour growth and activity. Treatment with vascular endothelial growth factor inhibitors would therefore seem a logical approach.</p> <p>Case presentation</p> <p>We describe a 23-year-old man with an exophytic capillary haemangioblastoma of the optic nerve head that was treated with intravitreal bevacizumab injections.</p> <p>Conclusion</p> <p>Unfortunately, treatment with intravitreal bevacizumab on three occasions had no effect on either tumour size or exudation in this patient.</p

Limb-girdle muscular dystrophy 1F is caused by a microdeletion in the transportin 3 gene

In 2001, we reported linkage of an autosomal dominant form of limb-girdle muscular dystrophy, limb-girdle muscular dystrophy 1F, to chromosome 7q32.1-32.2, but the identity of the mutant gene was elusive. Here, using a whole genome sequencing strategy, we identified the causative mutation of limb-girdle muscular dystrophy 1F, a heterozygous single nucleotide deletion (c.2771del) in the termination codon of transportin 3 (TNPO3). This gene is situated within the chromosomal region linked to the disease and encodes a nuclear membrane protein belonging to the importin beta family. TNPO3 transports serine/arginine-rich proteins into the nucleus, and has been identified as a key factor in the HIV-import process into the nucleus. The mutation is predicted to generate a 15-amino acid extension of the C-terminus of the protein, segregates with the clinical phenotype, and is absent in genomic sequence databases and a set of >200 control alleles. In skeletal muscle of affected individuals, expression of the mutant messenger RNA and histological abnormalities of nuclei and TNPO3 indicate altered TNPO3 function. Our results demonstrate that the TNPO3 mutation is the cause of limb-girdle muscular dystrophy 1F, expand our knowledge of the molecular basis of muscular dystrophies and bolster the importance of defects of nuclear envelope proteins as causes of inherited myopathies

Forest hydrology in Chile: Past, present, and future

This paper reviews the current knowledge of hydrological processes in Chilean temperate forests which extend along western South America from latitude 29° S to 56 ° S. This geographic region includes a diverse range of natural and planted forests and a broad sweep of vegetation, edaphic, topographic, geologic, and climatic settings which create a unique natural laboratory. Many local communities, endangered freshwater ecosystems, and downstream economic activities in Chile rely on water flows from forested catchments. This review aims to (i) provide a comprehensive overview of Chilean forest hydrology, to (ii) review prior research in forest hydrology in Chile, and to (iii) identify knowledge gaps and provide a vision for future research on forest hydrology in Chile. We reviewed the relation between native forests, commercial plantations, and other land uses on water yield and water quality from the plot to the catchment scale. Much of the global understanding of forests and their relationship with the water cycle is in line with the findings of the studies reviewed here. Streamflow from forested catchments increases after timber harvesting, native forests appear to use less water than plantations, and streams draining native forest yield less sediment than streams draining plantations or grassland/shrublands. We identified 20 key knowledge gaps such as forest groundwater systems, soil–plant-atmosphere interactions, native forest hydrology, and the effect of forest management and restoration on hydrology. Also, we found a paucity of research in the northern geographic areas and forest types (35-36 ° S); most forest hydrology studies in Chile (56 %) have been conducted in the southern area (Los Rios Region around 39-40 ° S). There is limited knowledge of the geology and soils in many forested areas and how surface and groundwater are affected by changes in land cover. There is an opportunity to advance our understanding using process-based investigations linking field studies and modeling. Through the establishment of a forest hydrology science “society” to coordinate efforts, regional and national-scale land use planning might be supported. Our review ends with a vision to advance a cross-scale collaborative effort to use new nation-wide catchment-scale networks Long-term Ecosystem Research (LTER) sites, to promote common and complementary techniques in these studies, and to conduct transdisciplinary research to advance sound and integrated planning of forest lands in Chile

Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy:Results of the EUROCONDOR Clinical Trial

The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and an Early Treatment of Diabetic Retinopathy Study (ETDRS) level of ≤35 were randomly assigned to one of three arms: placebo, somatostatin, or brimonidine. The primary outcome was the change in implicit time (IT) assessed by multifocal electroretinography between baseline and at the end of follow-up (96 weeks). There were 449 eligible patients allocated to brimonidine (n = 152), somatostatin (n = 145), or placebo (n = 152). When the primary end point was evaluated in the whole population, we did not find any neuroprotective effect of brimonidine or somatostatin. However, in the subset of patients (34.7%) with preexisting retinal neurodysfunction, IT worsened in the placebo group (P < 0.001) but remained unchanged in the brimonidine and somatostatin groups. In conclusion, the topical administration of the selected neuroprotective agents appears useful in preventing the worsening of preexisting retinal neurodysfunction. This finding points to screening retinal neurodysfunction as a critical issue to identify a subset of patients in whom neuroprotective treatment might be of benefit

Branch Retinal Vein Occlusion: Pathogenesis, Visual Prognosis, and Treatment Modalities

In branch retinal vein occlusion (BRVO), abnormal arteriovenous crossing with vein compression, degenerative changes of the vessel wall and abnormal hematological factors constitute the primary mechanism of vessel occlusion. In general, BRVO has a good prognosis: 50–60% of eyes are reported to have a final visual acuity (VA) of 20/40 or better even without treatment. One important prognostic factor for final VA appears to be the initial VA. Grid laser photocoagulation is an established treatment for macular edema in a particular group of patients with BRVO, while promising results for this condition are shown by intravitreal application of steroids or new vascular endothelial growth factor inhibitors. Vitrectomy with or without arteriovenous sheathotomy combined with removal of the internal limiting membrane may improve vision in eyes with macular edema which are unresponsive to or ineligible for laser treatment

A microarray study of MPP(+)-treated PC12 Cells: Mechanisms of toxicity (MOT) analysis using bioinformatics tools

BACKGROUND: This paper describes a microarray study including data quality control, data analysis and the analysis of the mechanism of toxicity (MOT) induced by 1-methyl-4-phenylpyridinium (MPP(+)) in a rat adrenal pheochromocytoma cell line (PC12 cells) using bioinformatics tools. MPP(+ )depletes dopamine content and elicits cell death in PC12 cells. However, the mechanism of MPP(+)-induced neurotoxicity is still unclear. RESULTS: In this study, Agilent rat oligo 22K microarrays were used to examine alterations in gene expression of PC12 cells after 500 μM MPP(+ )treatment. Relative gene expression of control and treated cells represented by spot intensities on the array chips was analyzed using bioinformatics tools. Raw data from each array were input into the NCTR ArrayTrack database, and normalized using a Lowess normalization method. Data quality was monitored in ArrayTrack. The means of the averaged log ratio of the paired samples were used to identify the fold changes of gene expression in PC12 cells after MPP(+ )treatment. Our data showed that 106 genes and ESTs (Expressed Sequence Tags) were changed 2-fold and above with MPP(+ )treatment; among these, 75 genes had gene symbols and 59 genes had known functions according to the Agilent gene Refguide and ArrayTrack-linked gene library. The mechanism of MPP(+)-induced toxicity in PC12 cells was analyzed based on their genes functions, biological process, pathways and previous published literatures. CONCLUSION: Multiple pathways were suggested to be involved in the mechanism of MPP(+)-induced toxicity, including oxidative stress, DNA and protein damage, cell cycling arrest, and apoptosis