Background:The regulation of glucose metabolism by estradiol is poorly defined. Results: We find that estradiol stimulates glucose metabolism in part by stimulating the production of fructose 2,6-bisphosphate by PFKFB3. Conclusion: PFKFB3 is a downstream target of estradiol required to stimulate glucose metabolism. Significance: Combined targeting of PFKFB3 and the estrogen receptor may prove beneficial to ER ϩ stage IV breast cancer patients.

Dendrimers are highly customizable nanopolymers with qualities that make them ideal for drug delivery. The high binding affinity of biotin/avidin provides a useful approach to fluorescently label synthesized dendrimer-conjugates in cells and tissues. In addition, biotin may facilitate delivery of dendrimers through the blood-brain barrier (BBB) via carrier-mediated endocytosis. The purpose of this research was to: (1) measure toxicity using lactate dehydrogenase (LDH) assays of generation (G)4 biotinylated and non-biotinylated poly(amidoamine) (PAMAM) dendrimers in a co-culture model of the BBB, (2) determine distribution of dendrimers in the rat brain, kidney, and liver following systemic administration of dendrimers, and (3) conduct atomic force microscopy (AFM) on rat brain sections following systemic administration of dendrimers. LDH measurements showed that biotinylated dendrimers were toxic to cell co-culture after 48 h of treatment. Distribution studies showed evidence of biotinylated and non-biotinylated PAMAM OPEN ACCESSMolecules 2013, 18 11538 dendrimers in brain. AFM studies showed evidence of dendrimers only in brain tissue of treated rats. These results indicate that biotinylation does not decrease toxicity associated with PAMAM dendrimers and that biotinylated PAMAM dendrimers distribute in the brain. Furthermore, this article provides evidence of nanoparticles in brain tissue following systemic administration of nanoparticles supported by both fluorescence microscopy and AFM.

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The interaction of biotinylated G4 poly (amidoamine) (PAMAM) dendrimer conjugates and G4 PAMAM dendrimers with in vitro models of the blood brain barrier (BBB) was evaluated using Langmuir Blodgett monolayer techniques, atomic force microscopy (AFM) and lactate dehydrogenase measures of cell membrane toxicity. Results indicate that both G4 and G4 biotinylated PAMAM dendrimers disrupt the composition of the liquid condensed (LC) and liquid expanded (LE) phases of the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid monolayer. The disruption is concentration dependent and more marked for G4 biotinylated PAMAMs. Lactate dehydrogenase (LDH) assays using endothelial cell culture models of the BBB indicate that biotinylation results in higher levels of toxicity than non-biotinylation. This approach provides valuable information to assess nanoparticle toxicity for drug delivery to the brain.

A 33-year old woman delivered a boy at 38 weeks via cesarean delivery. The neonate had diffuse erosions present at birth. Further evaluation revealed superficial annular erosions with central granulation tissue and desquamating borders on the occipital scalp, postauricular region, nape, and right calf (Figure 1). The mother had a 5-year history of pemphigus vulgaris and originally presented with erosions of the buccal mucosa, palate, nare, and conjunctival injection (Figure 2). Indirect immunofluorescence was positive for IgG cell surface antibodies (1:1260) and anti-desmoglein-3 antibodies on enzyme-linked immunosorbent assay (196 units). At the time of delivery, the mother exhibited erosions at the proximal nail folds of the feet. Neonatal pemphigus vulgaris was suspected. Serum testing of the neonate supported the diagnosis with positive IgG cell surface antibodies (1:320) and anti-desmoglein-3 antibodies (146 units).Pemphigus vulgaris is a blistering disease of the mucous membranes and skin secondary to autoantibodies directed towards desmoglein-1anddesmoglein-3. 1 Desmogleinsaretransmembraneproteins that function as a structural component of the desmosome and facilitate cell-to-cell adhesion. 1,2 Neonatal pemphigus vulgaris is a transient blistering disorder caused by passive transfer of maternal IgG autoantibodies across the placenta during pregnancy. 1 The risk of an infant developing neonatal pemphigus exists independently of levels of maternal antibody titers and/or mucocutaneous presentation at time ofgestation. [2][3][4] Thedistributionofulcerativelesionsintheneonatefailed to reflect the pattern visible in the mother. [1][2][3][4] Widespread disease in the neonate was a result of desmoglein-3 expression in the neonatal mucosal and cutaneous surfaces. Despite the severity of symptoms, the prognosis was favorable.Immunoglobulin levels transferred from mother to fetus are reduced by age 3 to 6 months. 2 Often, undetectable levels of antibody titers are seen in the infant shortly postdelivery; resolution of symptoms can be seen by age 3 weeks. 3 Therapy aims to support reepithelization of the skin and mucous membranes and prevent concomitant infection. 2,4 Treatment comprises emollients, topical corticosteroids, and anitbiotics. 4 Follow-up with monitoring of symptoms and levels of antibodies is recommended until age 1 year. 1 Although the literature fails to associate the degree of disease in the mother with that of the infant, efforts to reduce antibody levels in pregnant women is recommended. 3,4 This can be achieved with oral prednisone, intravenous immunoglobulin, or plasmapheresis. 1,4