Superoxide signaling and cell death in retinal ganglion cell axotomy: effects of metallocorroles

Injury to retinal ganglion cell (RGC) axons within the optic nerve causes apoptosis of the soma. We previously demonstrated that in vivo axotomy causes elevation of superoxide anion within the RGC soma, and that this occurs 1-2 days before annexin-V positivity, a marker of apoptosis. Pegylated superoxide dismutase delivery to the RGC prevents the superoxide elevation and rescues the soma. Together, these results imply that superoxide is an upstream signal for apoptosis after axonal injury in RGCs. We then studied metallocorroles, potent superoxide dismutase mimetics, which we had shown to be neuroprotective in vitro and superoxide scavengers in vivo for RGCs. RGCs were retrograde labeled with the fluorescent dye 4Di-10Asp, and then axotomized by intraorbital optic nerve transection. Iron(III) 2,17-bis-sulfonato-5,10,15-tris(pentafluorophenyl)corrole (Fe(tpfc)(SO(3)H)(2)) (Fe-corrole) was injected intravitreally. Longitudinal imaging of RGCs was performed and the number of surviving RGCs enumerated. There was significantly greater survival of labeled RGCs with Fe-corrole, but the degree of neuroprotection was relatively less than that predicted by their ability to scavenge superoxide-This implies an unexpected complexity in signaling of apoptosis by reactive oxygen species.     

CMS: An adapter molecule involved in cytoskeletal rearrangements

Cas ligand with multiple Src homology (SH) 3 domains (CMS) is an ubiquitously expressed signal transduction molecule that interacts with the focal adhesion protein p130(Cas). CMS contains three SH3 in its NH2 terminus and proline-rich sequences in its center region. The latter sequences mediate the binding to the SH3 domains of p130(Cas), Src-family kinases, p85 subunit of phosphatidylinositol 3-kinase, and Grb2. The COOH-terminal region contains putative actin binding sites and a coiled-coil domain that mediates homodimerization of CMS. CMS is a cytoplasmic protein that colocalizes with F-actin and p130(Cas) to membrane ruffles and leading edges of cells. Ectopic expression of CMS in COS-7 cells resulted in alteration in arrangement of the actin cytoskeleton. We observed a diffuse distribution of actin in small dots and less actin fiber formation. Altogether, these features suggest that CMS functions as a scaffolding molecule with a specialized role in regulation of the actin cytoskeleton.     

Pregnancy Dermatoses

Some aspects regarding the etiology and the nosologic classification of various pregnancy dermatoses are highly controversial. While some authors highlight the existence of premises allowing several skin disorders to be re-grouped within broader disease concepts, others underline the absence of clear, undisputed etiopathogenetic data that could support such classifications. This review exhaustively analyzes the various pregnancy dermatoses (pemphigoid gestationis, intrahepatic cholestasis of pregnancy, impetigo herpetiformis, polymorphic eruption of pregnancy, and the papular dermatoses of pregnancy [prurigo of pregnancy, pruritic folliculitis of pregnancy, and the new classification, atopic eruption of pregnancy]) in an attempt to shed light over this confusing and disputed domain, while subsequently offering an algorithmic approach to their diagnosis and management. While for pemphigus gestationis, intrahepatic cholestasis of pregnancy, and impetigo herpetiformis, specific diagnostic tests such as histopathology, immunofluorescence, or laboratory investigations will confirm the diagnosis, the identification of the other types of pregnancy dermatoses is based only on clinical criteria. In this context, the review argues for the inclusion of the whole group represented by the papular dermatoses of pregnancy within the broad spectrum of polymorphic eruption of pregnancy, separating each of these entities by focusing on their onset: early-onset polymorphic eruption of pregnancy (comprising prurigo of pregnancy, pruritic folliculitis of pregnancy, and atopic eruption of pregnancy) and late-onset polymorphic eruption of pregnancy. In light of the same practical approach guiding it, the review provides updated treatment strategies for each of these conditions.     

NHERF1: molecular brake on the PI3K pathway in breast cancer

The adaptor protein NHERF1/EBP50 (Na/H exchanger regulatory factor 1/ezrin-radixin-moesin-binding phosphoprotein 50) emerged recently as an important player in breast cancer progression. Consisting of two tandem PDZ domains linked to a carboxyl-terminal ezrin-binding region, NHERF1 assembles macromolecular complexes at the apical membrane of epithelial cells in many epithelial tissues, including the mammary gland. Involved initially in trafficking and regulation of transmembrane ion transporters and G protein-coupled receptors, NHERF1 also couples molecules involved in cell growth, such as the platelet-derived growth factor receptor (PDGFR) and PTEN (phosphatase and tensin homolog deleted on chromosome 10). In the previous issue of Breast Cancer Research, Pan and colleagues show an inhibitory action of NHERF1 on the phosphoinositide-3 kinase (PI3K)/Akt pathway in breast cancer cells via interaction of NHERF1 with PTEN, the physiological antagonist of the PI3K. Additionally, they show that NHERF1 expression confers susceptibility to PDGFR pharmacological inhibition depending on the presence of PTEN tumor suppressor.     

Eating Habits in Patients with Familial Hypercholesterolemia from North-Eastern Romania

(1) Background: Familial hypercholesterolemia (FH) is a genetic autosomal dominant disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL) that develops deposits of lipids in the arterial wall. Since it is underdiagnosed and undertreated, the disease has a high risk of premature cardiovascular disease and death. Patients are not always aware of the changes they should make in their diet. Thus, our study aimed to evaluate through a food frequency questionnaire their eating habits. (2) Methods: We included 70 patients with FH and 20 subjects in a control group that were evaluated through a physical examination and blood tests. They also completed a food frequency questionnaire. (3) Results: Throughout our study, we observed several aspects: regardless of age, patients with FH had higher carbohydrate intakes compared to the control group; from the same group, a positive correlation was observed between salami intake and the levels of glucose and glycated hemoglobin. Moreover, the sour cream preference was associated with higher liver function tests. In the control group, we observed a higher intake of pasta and fast food and fewer fruit portions. (4) Conclusions: As far as we know, this is the first study from Romania that evaluated the eating habits of patients diagnosed with FH. Our study reveals that, although patients with FH avoid junk food, they still have a high intake of carbohydrates when compared to the control group. Further research is needed in order to get a comprehensive nutritional evaluation of these patients.