Endovascular Treatment of Transverse-Sigmoid Sinus Dural Arteriovenous Malformations Presenting as Pulsatile Tinnitus

Transverse-sigmoid sinus dural arteriovenous malformations (DAVM) are uncommon vascular lesions for which complete cure may be difficult to obtain. A wide variety of treatments for these lesions include observation, arterial compression, surgical resection, and endovascular embolization. We propose that transverse-sigmoid sinus DAVM can be completely cured by occluding the ipsilateral dural sinus with detachable balloon and Guglielmi detachable coils (GDC) coils before arterial feeder embolization with histoacryl. Three patients who presented with pulsatile tinnitus and normal magnetic resonance imaging (MRI) studies underwent angiography, which demonstrated transverse-sigmoid sinus DAVM. All three patients wer treated with retrograde transvenous sinus embolization with complete occlusion of the transverse-sigmoid sinus with detachable balloons and GDC coils with preservation of the vein of Labbé. Subsequently, the various feeders from the external carotid artery were embolized. The tentorial arteries arising from the ipsilateral internal carotid arteries were not embolized in any of the cases, which were still contributing to the DAVM. Complete cure with thrombosis of the tentorial branch of the internal carotid artery (ICA) was seen on follow-up angiogram 1 day after embolization in one patient and on 4-week and 6-week follow-up angiograms in the other two patients. Complete occlusion of the transverse sinus proximal to the vein of Labbé, in spite of incomplete arterial feeder embolization, can result in complete cure of the transversesinus dural AVF if adequate time is given for the remaining feeders to occlude, once the fistula is obliterated.     

Tonicity response element binding protein associated with neuronal cell death in the experimental diabetic retinopathy

AIM:To studythe contribution of tonicity response element binding protein (TonEBP) in retinal ganglion cell (RGC) death of diabetic retinopathy (DR).METHODS:Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin (STZ). Control mice received vehicle (phosphate-buffered saline). All mice were killed 2mo after injections, and the extent of cell death and the protein expression levels of TonEBP and aldose reductase (AR) were examined.RESULTS:The TonEBP and AR protein levels and the death of RGC were significantly increased in the retinas of diabetic mice compared with controls 2mo after the induction of diabetes. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL)-positive signals co-localized with TonEBP immunoreactive RGC. These changes were increased in the diabetic retinas compared with controls.CONCLUSION:The present data show that AR and TonEBP are upregulated in the DR and TonEBP may contribute to apoptosis of RGC in the DR.     

Sphingomyelinase-Like Phosphodiesterase 3b Expression Levels Determine Podocyte Injury Phenotypes in Glomerular Disease

Diabetic kidney disease (DKD) is the most common cause of ESRD in the United States. Podocyte injury is an important feature of DKD that is likely to be caused by circulating factors other than glucose. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating factor found to be elevated in the serum of patients with FSGS and causes podocyte αVβ₃ integrin-dependent migration in vitro. Furthermore, αVβ₃ integrin activation occurs in association with decreased podocyte-specific expression of acid sphingomyelinase-like phosphodiesterase 3b (SMPDL3b) in kidney biopsy specimens from patients with FSGS. However, whether suPAR-dependent αVβ₃ integrin activation occurs in diseases other than FSGS and whether there is a direct link between circulating suPAR levels and SMPDL3b expression in podocytes remain to be established. Our data indicate that serum suPAR levels are also elevated in patients with DKD. However, unlike in FSGS, SMPDL3b expression was increased in glomeruli from patients with DKD and DKD sera-treated human podocytes, where it prevented αVβ₃ integrin activation by its interaction with suPAR and led to increased RhoA activity, rendering podocytes more susceptible to apoptosis. In vivo, inhibition of acid sphingomyelinase reduced proteinuria in experimental DKD but not FSGS, indicating that SMPDL3b expression levels determined the podocyte injury phenotype. These observations suggest that SMPDL3b may be an important modulator of podocyte function by shifting suPAR-mediated podocyte injury from a migratory phenotype to an apoptotic phenotype and that it represents a novel therapeutic glomerular disease target.     

Protective effects of Korean red ginseng against radiation-induced apoptosis in human HaCaT keratinocytes

Radiation-induced oral mucositis is a dose-limiting toxic side effect for patients with head and neck cancer. Numerous attempts at improving radiation-induced oral mucositis have not produced a qualified treatment. Ginseng polysaccharide has multiple immunoprotective effects. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in the human keratinocyte cell line HaCaT and in an in vivo zebrafish model. Radiation inhibited HaCaT cell proliferation and migration in a cell viability assay and wound healing assay, respectively. KRG protected against these effects. KRG attenuated the radiation-induced embryotoxicity in the zebrafish model. Irradiation of HaCaT cells caused apoptosis and changes in mitochondrial membrane potential (MMP). KRG inhibited the radiation-induced apoptosis and intracellular generation of reactive oxygen species (ROS), and stabilized the radiation-induced loss of MMP. Western blots revealed KRG-mediated reduced expression of ataxia telangiectasia mutated protein (ATM), p53, c-Jun N-terminal kinase (JNK), p38 and cleaved caspase-3, compared with their significant increase after radiation treatment. The collective results suggest that KRG protects HaCaT cells by blocking ROS generation, inhibiting changes in MMP, and inhibiting the caspase, ATM, p38 and JNK pathways.