Formation and Stability of Synaptic Receptor Domains

Neurotransmitter receptor molecules, concentrated in postsynaptic domains along with scaffold and a number of other molecules, are key regulators of signal transmission across synapses. Employing experiment and theory, we develop a quantitative description of synaptic receptor domains in terms of a reaction-diffusion model. We show that interactions between only receptor and scaffold molecules, together with the rapid diffusion of receptors on the cell membrane, are sufficient for the formation and stable characteristic size of synaptic receptor domains. Our work reconciles long-term stability of synaptic receptor domains with rapid turnover and diffusion of individual receptors.Comment: 5 pages, 3 figures, Supplementary Materia

Endovascular Treatment of Renal Artery Bifurcation Stenoses with Branched Balloon Angioplasty

An 85-year-old man with left sided single kidney presented with end-stage renal failure after an acute intestinal bleeding. A complex bifurcational stenoses distally to a 6 months previously implanted ostial stent in the left renal artery was found on duplex imaging and angiogram. These two de-novo stenoses in the distal main renal artery and the proximal segment of the lower branch were simultaneously treated with a ultra-low profile, monorail bifurcation balloon catheter system (Avion Bifurcation RX2™, Invatec, Italy) that consists of a main vessel balloon (20/3.5mm) and a side vessel balloon (20/2.75mm). One day and three months postinterventionally, duplex ultrasound demonstrated no recurrent stenoses. Bifurcation balloon catheter systems for complex renal artery stenosis are discussed

Dynamics of glycine receptor insertion in the neuronal plasma membrane

The exocytosis site of newly synthesized glycine receptor was defined by means of a morphological assay to characterize its export from the trans-Golgi Network to the plasma membrane. This was achieved by expressing in transfected neurons an alpha1 subunit bearing an N-terminal tag selectively cleavable from outside the cell by thrombin. This was combined with a transient temperature-induced block of exocytic transport that creates a synchronized exocytic wave. Immunofluorescence microscopy analysis of the cell surface appearance of newly synthesized receptor revealed that exocytosis mainly occurred at nonsynaptic sites in the cell body and the initial portion of dendrites. At the time of cell surface insertion, the receptors existed as discrete clusters. Quantitative analysis showed that glycine receptor clusters are stable in size and subsequently appeared in more distal dendritic regions. This localization resulted from diffusion in the plasma membrane and not from exocytosis of transport vesicles directed to dendrites. Kinetic analysis established a direct substrate-product relationship between pools of somatic and dendritic receptors. This indicated that clusters represent intermediates between newly synthesized and synaptic receptors. These results support a diffusion-retention model for the formation of receptor-enriched postsynaptic domains and not that of a vectorial intracellular targeting to synapses

A Rare Case of Jejunal Arterio-Venous Fistula: Treatment with Superselective Catheter Embolization with a Tracker-18 Catheter and Microcoils

Arterio-venous fistulas may develop spontaneously, following trauma or infection, or be iatrogenic in nature. We present a rare case of a jejunal arterio- venous fistula in a 35-year-old man with a history of pancreatic head resection that had been performed two years previously because of chronic pancreatitis. The patient was admitted with acute upper abdominal pain, vomiting and an abdominal machinery-type bruit. The diagnosis of a jejunal arterio-venous fistula was established by MR imaging. Transfemoral angiography was performed to assess the possibility of catheter embolization. The angiographic study revealed a small aneurysm of the third jejunal artery, abnormal early filling of dilated jejunal veins and marked filling of the slightly dilated portal vein (13-14 mm). We considered the presence of segmental portal hypertension. The patient was treated with coil embolization in the same angiographic session. This case report demonstrates the importance of auscultation of the abdomen in the initial clinical examination. MR imaging and color Doppler ultrasound are excellent noninvasive tools in establishing the diagnosis. The role of interventional radiological techniques in the treatment of early portal hypertension secondary to jejunal arterio-venous fistula is discussed at a time when this condition is still asymptomatic. A review of the current literature is include

O-Vanillin attenuates the TLR2 mediated tumor-promoting phenotype of microglia

Malignant gliomas are primary brain tumors with poor prognoses. These tumors are infiltrated by brain intrinsic microglia and peripheral monocytes which promote glioma cell invasion. In our previous studies, we discovered that the activation of Toll-like receptor 2 (TLR2) on microglia/brain macrophages converts them into a protumorigenic phenotype through the induction of matrix metalloproteinases (MMP) 9 and 14. In the present study, we used in vitro and in situ microglia-glioma interaction experimental models to test the impact of a novel inhibitor of TLR 2, ortho vanillin (O-Vanillin) to block TLR2 mediated microglia protumorigenic phenotype. We demonstrate that O-Vanillin inhibits the TLR2 mediated upregulation of MMP 9, MMP 14, IL 6 and iNOS expression. Similarly, the glioma supernatant induced MMP 9 and MMP 14 expression in murine and human microglia is abrogated by O-Vanillin treatment. O-Vanillin is not toxic for microglia, astrocytes or oligodendrocytes. Glioma growth in murine brain slice cultures is significantly reduced after treatment with O-Vanillin, and this reduced glioma growth depends on the presence of microglia. In addition, we also found that O-Vanillin inhibited the glioma induced proliferation of murine primary microglia. In summary, O-Vanillin attenuates the pro-tumorigenic phenotype of microglia/brain macrophages and thus qualifies as a candidate for glioma therapy

Evaluation of Adaptive Changes by Non-Invasive Imaging in Hepatic Vein Outflow Obstruction

Hepatic vein outflow obstruction induces remarkable changes of intra–hepatic blood circulation; the significance of these changes remains uncertain. Six patients with obstruction of the hepatic veins were evaluated by duplex Doppler ultrasound and computed tomography. The adaptive changes secondary to obstruction were analyzed and their significance was correlated with the clinical findings. Four patients presenting unilateral hepatic vein occlusion had unilateral reversed portal flow. Two of them, with lobar liver atrophy and contralateral compensatory hypertrophy required operation; the other two, with normal appearance of the liver, benefitted from conservative treatment. Two patients with bilateral hepatic vein occlusion, intra-hepatic bypasses, bilateral lobar atrophy and caudate lobe hypertrophy, received operations. Intrahepatic unilateral portal flow reversal compensates for unilateral hepatic outflow obstruction. The combination of complete or subtotal hepatic vein obstruction and atrophy–hypertrophy complex predicates advanced disease despite flow reversal or spontaneous shunt

Rectal Bleeding Associated With Chronic Pancreatitis

Pseudocyst formation, with its attendant complications of compression, rupture, bleeding and fistula formation, is a well known complication of chronic pancreatitis. In 1966 Berne and Edmondson drew attention to the often fatal outcome of pancreatico-colonic fistula complicated by hemorrhage. We present two cases of this rare complication of chronic pancreatitis as defined by the Marseille classification

Wound healing and hyper-hydration - a counter intuitive model

Winters seminal work in the 1960s relating to providing an optimal level of moisture to aid wound healing (granulation and re-epithelialisation) has been the single most effective advance in wound care over many decades. As such the development of advanced wound dressings that manage the fluidic wound environment have provided significant benefits in terms of healing to both patient and clinician. Although moist wound healing provides the guiding management principle confusion may arise between what is deemed to be an adequate level of tissue hydration and the risk of developing maceration. In addition, the counter-intuitive model ‘hyper-hydration’ of tissue appears to frustrate the moist wound healing approach and advocate a course of intervention whereby tissue is hydrated beyond what is a normally acceptable therapeutic level. This paper discusses tissue hydration, the cause and effect of maceration and distinguishes these from hyper-hydration of tissue. The rationale is to provide the clinician with a knowledge base that allows optimisation of treatment and outcomes and explains the reasoning behind wound healing using hyper-hydration

In situ visualization and dynamics of newly synthesized proteins in rat hippocampal neurons

Protein translation has been implicated in different forms of synaptic plasticity, but direct in situ visualization of new proteins is limited to one or two proteins at a time. Here we describe a metabolic labeling approach based on incorporation of noncanonical amino acids into proteins followed by chemoselective fluorescence tagging by means of 'click chemistry'. After a brief incubation with azidohomoalanine or homopropargylglycine, a robust fluorescent signal was detected in somata and dendrites. Pulse-chase application of azidohomoalanine and homopropargylglycine allowed visualization of proteins synthesized in two sequential time periods. This technique can be used to detect changes in protein synthesis and to evaluate the fate of proteins synthesized in different cellular compartments. Moreover, using strain-promoted cycloaddition, we explored the dynamics of newly synthesized membrane proteins using single-particle tracking and quantum dots. The newly synthesized proteins showed a broad range of diffusive behaviors, as would be expected for a pool of labeled proteins that is heterogeneous