Radiofrequency ablation of superficial and perforator veins for venous insufficiency has emerged as a leading alternative to traditional vein stripping operations. This percutaneous technique can be ...performed in less than an hour using local anesthetic or sedation. The VNUS Closure catheters (VNUS Medical Technologies, San Jose, California) work by resistive heating in the vein wall that is constantly monitored through a feedback loop to the VNUS Closure generator. Side effects are less than with other endovenous ablation techniques and patients resume normal activity immediately. The new ClosureFAST catheter is an important advancement that combines the speed of endovenous laser ablation with the expected fewer side effects of radiofrequency ablation.
Retinal ischemia is a major cause of vision loss and impairment and a common underlying mechanism associated with diseases such as glaucoma, diabetic retinopathy, and central retinal artery ...occlusion. The regenerative capacity of the diseased human retina is limited. Our previous studies have shown the neuroprotective effects of intravitreal injection of mesenchymal stem cells (MSC) and MSC-conditioned medium in retinal ischemia in rats. Based upon the hypothesis that the neuroprotective effects of MSCs and conditioned medium are largely mediated by extracellular vesicles (EVs), MSC derived EVs were tested in an in-vitro oxygen-glucose deprivation (OGD) model of retinal ischemia. Treatment of R28 retinal cells with MSC-derived EVs significantly reduced cell death and attenuated loss of cell proliferation. Mechanistic studies on the mode of EV endocytosis by retinal cells were performed in vitro. EV endocytosis was dose- and temperature-dependent, saturable, and occurred via cell surface heparin sulfate proteoglycans mediated by the caveolar endocytic pathway. The administration of MSC-EVs into the vitreous humor 24 h after retinal ischemia in a rat model significantly enhanced functional recovery, and decreased neuro-inflammation and apoptosis. EVs were taken up by retinal neurons, retinal ganglion cells, and microglia. They were present in the vitreous humor for four weeks after intravitreal administration, with saturable binding to vitreous humor components. Overall, this study highlights the potential of MSC-EV as biomaterials for neuroprotective and regenerative therapy in retinal disorders.
Nylon 6/clay nanocomposites were studied by dielectric relaxation spectroscopy (DRS) to correlate morphology and microstructure with relaxation behavior of the polymer matrix at the molecular level. ...Partially exfoliated clay microstructure was achieved by extruding nylon 6 with surfactant-treated montmorillonite clays. A new on-line dielectric slit die sensor was used to examine the melt state properties during extrusion compounding. Solid state properties were probed by off-line DRS over a temperature range from −50 to 180
°C in a frequency range from 10
−3 to 10
6
Hz. Using non-linear regression methods in conjunction with the temperature–frequency positions of relaxations observed in the dielectric loss data, the experimental data were fit with the Havriliak–Negami and Cole–Cole dielectric relaxation functions corrected for electrode polarization and DC conductivity. Characteristic frequency, relaxation strength, and DC conductivities were extracted from curves with overlapping relaxation modes. Two dielectric relaxations were observed in the composite melt: the
α relaxation associated with molecular segmental motion, and a Maxwell–Wagner relaxation (MW) resulting from interfacial polarization at the resin/clay interface. Analysis of the solid-state data yielded a comprehensive master plot of dielectric relaxations attributed to segmental and local molecular dynamics and other relaxations resulting from water and Maxwell–Wagner interfacial polarization. The impact of clay fillers is seen in nearly all relaxation processes changing both characteristic frequency and strength of the relaxation.
We previously described the phenomenon of retinal ischemic pre-conditioning (IPC) and we have shown the role of various signaling proteins in the protective pathways, including the mitogen-activated ...protein kinase p38. In this study we examined the role in IPC of mitogen-activated protein kinase phosphatase-1 (MKP-1), which inactivates p38. Ischemia was produced by elevation of intraocular pressure above systolic arterial blood pressure in adult Wistar rats. Preconditioning was produced by transient retinal ischemia for 5 min, 24 h prior to ischemia. Small interfering RNA (siRNA) to MKP-1 or a control non-silencing siRNA, was injected into the vitreous 6 h prior to IPC. Recovery was assessed by electroretinography (ERG) and histology. The a-and b-waves, and oscillatory potentials (OPs), measured before and 1 week after ischemia, were then normalized relative to pre-ischemic baseline, and corrected for diurnal variation in the normal non-ischemic eye. The P2, or post-photoreceptor component of the ERG (which reflects function of the rod bipolar cells in the inner retina), was derived using the Hood-Birch model. MKP-1 was localized in specific retinal cells using immunohistochemistry; levels of mitogen-activated protein kinases were measured using Western blotting. Injection of siRNA to MKP-1 significantly attenuated the protective effect of IPC as reflected by decreased recovery of the electroretinogram a and b-waves and the P2 after ischemia. The injection of siRNA to MKP-1 reduced the number of cells in the retinal ganglion cell and outer nuclear layers after IPC and ischemia. Blockade of MKP-1 by siRNA also increased the activation of p38 at 24 h following IPC. MKP-1 siRNA did not alter the levels of phosphorylated jun N-terminal kinase (JNK) or extracellular signal-regulated kinase (ERK) after IPC. The results suggest the involvement of dual-specificity phosphatase MKP-1 in IPC and that MKP-1 is involved in IPC by regulating levels of activated MAPK p38.
► Ischemic pre-conditioning dramatically protects the retina from ischemic injury. ► We showed the involvement of MKP-1 in ischemic preconditioning. ► The results suggest that MKP-1 regulates levels of p38.
Dielectric and optical transmission measurements obtained during processing of polymer/clay composites yielded quantitative information about the extent of clay exfoliation in the polymer matrix. ...Measurements were made using an instrumented slit die that was situated at the exit of a twin screw extruder. Nylon 6, 11 and 12 resins were compounded with several organo modified montmorillonite clays. Dielectric and optical data were correlated with off-line transmission electron microscopy. Dielectric observations revealed a large Maxwell–Wagner (MW) relaxation whose characteristic frequency reflects an
RC time constant associated with the conduction of ions and the polarization of the resin/clay interface. Optical transmission measurements showed that transmission increased with increasing extent of exfoliation because light scattering due to aggregate clay particles is reduced as the particles exfoliate nanosize silicate flakes. Extent of exfoliation models, based on MW relaxation time and its relationship to interfacial polarization, and based on optical transmission measurements, are developed.
5-aminolevulinic acid (ALA) is used during resection of malignant gliomas due to its fluorescence properties and has been shown to render resection more effective than resection without ALA guidance. ...The aim of this narrative review is to categorize the adverse effects of ALA relevant to anesthesia providers. Intraoperative hypotension, porphyria-related side effects, alterations in blood chemistry and coagulation, photosensitivity, and increased levels of liver enzymes have all been reported. We also sought to examine the impact of dosage and timing of oral administration on efficacy of ALA and on these side effects. Twenty-seven studies met our inclusion criteria of patients undergoing craniotomy for glioma resection using ALA and occurrence of at least one adverse effect. The results of these studies showed that there was heterogeneity in levels of intraoperative hypotension, with some reporting an incidence as high as 32%, and that hypotension was associated with antihypertensive medication use. Clinical symptoms of porphyria, such as gastrointestinal disturbance, were less commonly reported. Photosensitivity of the skin after 5-ALA administration was well documented particularly in patients exposed to light; however, adverse effects on the eye were not adequately studied. Elevation in liver enzymes was a common finding postoperatively but was often clinically insignificant. The timing of oral administration presents practical issues for the preoperative management of patients undergoing resection with ALA. We provide guidance for perioperative management of patients who receive ALA for brain tumor resection. Controlled studies with adequate statistical power are required to further understand and prevent the adverse effects of ALA.
After an acute ischemia/reperfusion of the rat retina, the activation of cytotoxic proteases, including calpain, results in necrosis and apoptosis of retinal ganglion cells resulting in their ...degeneration. Using a systemically administered calpain inhibitor that crosses the blood-retinal barrier would provide for novel systemic intervention that protects the retina from acute injury and loss of function. Herein, we study a novel calpain peptide inhibitor, cysteic-leucyl-argininal (CYLA), in an in-vivo rat model of retinal ischemia to determine functional protection using electroretinography. The CYLA prodrug was administered intraperitoneally before and/or after ischemia-reperfusion at concentrations of 20-40 mg/kg. We found that administering 20 mg/kg of CYLA only after ischemia provides significant preservation of retinal function.
Nitric oxide synthase (NOS), the enzyme that catalyzes the formation of nitric oxide from L-arginine, exists in three major isoforms, neuronal, endothelial, and immunologic. Neuronal and endothelial ...isoforms are constitutively expressed, and require calcium for activation. Both of these isoforms can be induced (i.e., new protein synthesis occurs) under appropriate conditions. The immunologic isoform is not constitutively expressed, and requires induction usually by immunologic activation; calcium is not necessary for its activation. Neuronal and immunologic NOS have been detected in the retina. Neuronal NOS may be responsible for producing nitric oxide in photoreceptors and bipolar cells. Nitric oxide stimulates guanylate cyclase of photoreceptor rod cells and increases calcium channel currents. In the retina of cats, NOS inhibition impairs phototransduction as assessed by the electroretinogram. Inducible nitric oxide synthase, found in Müller cells and in retinal pigment epithelium, may be involved in normal phagocytosis of the retinal outer segment, in infectious and ischemic processes, and in the pathogenesis of diabetic retinopathy. Nitric oxide contributes to basal tone in the retinal circulation. To date, findings are conflicting with respect to its role in retinal autoregulation. During glucose and oxygen deprivation, nitric oxide may increase blood flow and prevent platelet aggregation, but it may also mediate the toxic effects of excitatory amino acid release. This reactive, short-lived gas is involved in diverse processes within the retina, and its significance continues to be actively studied.
Melt state properties of nylon-11 and its exfoliated silicate nanocomposite were monitored during extrusion compounding using an on-line dielectric slit die sensor, and solid-state properties were ...probed off-line below the melting temperature by a dielectric spectrometer. A comprehensive relaxation master map for nylon-11 and its exfoliated clay nanocomposite featuring six relaxation modes in both melt and semicrystalline states revealed changes in molecular dynamics upon the addition of nanofillers. α relaxation was observed in the neat resin as well as the composite, and a Maxwell−Wagner−Sillars (MWS) relaxation was detected in the composite melt yet absent from the neat molten nylon. The MWS relaxation mode, which exhibited a broader relaxation time distribution and a much greater dielectric intensity compared to the α relaxation, resulted from polarization at the filler/polymer interfaces. MWS can be used to distinguish the neat polymer from the composite during real-time processing. The presence of exfoliated clay particles accelerated the α relaxation dynamics in the semicrystalline state as delaminated silicate platelets diminished the intermolecular cooperativity of the amorphous chains. Randomization of molecular dipoles upon increasing temperature was only observed in the neat nylon. Hindered molecular dipole orientation due to the rigid silicate fillers in the nanocomposite was observed.
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