Inhibition of cAMP/PKA Pathway Protects Optic Nerve Head Astrocytes against Oxidative Stress by Akt/Bax Phosphorylation-Mediated Mfn1/2 Oligomerization.

Glaucoma is characterized by a progressive optic nerve degeneration and retinal ganglion cell loss, but the underlying biological basis for the accompanying neurodegeneration is not known. Accumulating evidence indicates that structural and functional abnormalities of astrocytes within the optic nerve head (ONH) have a role in glaucomatous neurodegeneration. Here, we investigate the impact of activation of cyclic adenosine 3',5'-monophosphate (cAMP)/protein kinase A (PKA) pathway on mitochondrial dynamics of ONH astrocytes exposed to oxidative stress. ONH astrocytes showed a significant loss of astrocytic processes in the glial lamina of glaucomatous DBA/2J mice, accompanied by basement membrane thickening and collagen deposition in blood vessels and axonal degeneration. Serial block-face scanning electron microscopy data analysis demonstrated that numbers of total and branched mitochondria were significantly increased in ONH astrocytes, while mitochondrial length and volume density were significantly decreased. We found that hydrogen peroxide- (H2O2-) induced oxidative stress compromised not only mitochondrial bioenergetics by reducing the basal and maximal respiration but also balance of mitochondrial dynamics by decreasing dynamin-related protein 1 (Drp1) protein expression in rat ONH astrocytes. In contrast, elevated cAMP by dibutyryl-cAMP (dbcAMP) or isobutylmethylxanthine treatment significantly increased Drp1 protein expression in ONH astrocytes. Elevated cAMP exacerbated the impairment of mitochondrial dynamics and reduction of cell viability to oxidative stress in ONH astrocytes by decreasing optic atrophy type 1 (OPA1), and mitofusin (Mfn)1/2 protein expression. Following combined treatment with H2O2 and dbcAMP, PKA inhibition restored mitochondrial dynamics by increasing mitochondrial length and decreasing mitochondrial number, and this promoted cell viability in ONH astrocytes. Also, PKA inhibition significantly promoted Akt/Bax phosphorylation and Mfn1/2 oligomerization in ONH astrocytes. These results suggest that modulation of the cAMP/PKA signaling pathway may have therapeutic potential by activating Akt/Bax phosphorylation and promoting Mfn1/2 oligomerization in glaucomatous ONH astrocytes

Elevated intracellular cAMP exacerbates vulnerability to oxidative stress in optic nerve head astrocytes.

Glaucoma is characterized by a progressive loss of retinal ganglion cells and their axons, but the underlying biological basis for the accompanying neurodegeneration is not known. Accumulating evidence indicates that structural and functional abnormalities of astrocytes within the optic nerve head (ONH) have a role. However, whether the activation of cyclic adenosine 3',5'-monophosphate (cAMP) signaling pathway is associated with astrocyte dysfunction in the ONH remains unknown. We report here that the cAMP/protein kinase A (PKA) pathway is critical to ONH astrocyte dysfunction, leading to caspase-3 activation and cell death via the AKT/Bim/Bax signaling pathway. Furthermore, elevated intracellular cAMP exacerbates vulnerability to oxidative stress in ONH astrocytes, and this may contribute to axonal damage in glaucomatous neurodegeneration. Inhibition of intracellular cAMP/PKA signaling activation protects ONH astrocytes by increasing AKT phosphorylation against oxidative stress. These results strongly indicate that activation of cAMP/PKA pathway has an important role in astrocyte dysfunction, and suggest that modulating cAMP/PKA pathway has therapeutic potential for glaucomatous ONH degeneration

Atypical iliac vein compression in patients with symptomatic May–Thurner syndrome

PURPOSEWe aimed to investigate the incidence, etiology, treatment, and clinical course of atypical iliac vein compressions (AIVCs) among patients with May–Thurner syndrome (MTS).METHODSA total of 173 patients who presented with MTS were retrospectively analyzed at a single center. Computed tomographic venography (CTV) was used to diagnose MTS. An AIVC was defined as the compression of the left common iliac vein (LCIV) by structures other than the right common iliac artery (RCIA) or the compression of other venous structures in the pelvic cavity instead of the LCIV. The patients with AIVC were categorized into the LCIV compression group (category A) and non-LCIV compression group (category B).RESULTSTen patients with AIVC were identified (5.8%; male/female, 5/5), five in category A and five in category B. The median age of patients was 76 years (range, 51–94 years), and the median follow-up duration was 388 days (range, 12–4694 days). In category A, the LCIVs were compressed by the left common iliac artery (LCIA) (n=2), uterine leiomyoma (n=1), LCIA aneurysm (n=1), and RCIA aneurysm (n=1). In category B, the right common iliac veins were compressed by the RCIA (n=4) and L5 osteophyte (n=1). Endovascular treatment, including balloon angioplasty and stent placement, was performed in six patients, three from each group. Three patients underwent conservative treatment due to their advanced age and comorbidities. Endovascular aneurysm repair was performed in one patient with RCIA aneurysm. Follow-up images were available for six patients, and all of them had patent venous flow.CONCLUSIONThe AIVC had an incidence of 5.8% (10/173) among symptomatic MTS patients and wide spectrum of etiologies. Pathogenesis-tailored endovascular treatments are safe and effective

Spontaneous aortic rupture in a patient with neurofibromatosis type 1

Neurofibromatosis type I (NF-1) is a rare autosomal dominant genetic disorder occurring in 1 in 3,000 individuals. Vasculopathy is a rarely reported finding in patients with NF-1. Here, we report a case of recurrent aortic pseudoaneurysm after endovascular aneurysm repair in a 49-year-old male patient with NF-1. On the sixth postoperative day following a successful open surgical repair of an aortic pseudoaneurysm, he developed hemoperitoneum due to a delayed rupture of the mesenteric artery branch. This was treated with endovascular coil embolization. We report the clinical features and histologic findings of this rare vascular disorder with a review of the relevant literature

New Heteroleptic Cobalt Precursors for Deposition of Cobalt-Based Thin Films

A new series of heteroleptic complexes of cobalt were synthesized using aminoalkoxide and ??-diketonate ligands. The complexes, [Co(dmamp)(acac)]2 (3), [Co(dmamp)(tfac)]2 (4), [Co(dmamp)(hfac)]2 (5), [Co(dmamp)(tmhd)]2 (6), and [Co(dmamb)(tmhd)]2 (7), were prepared by two-step substitution reactions and studied using Fourier transform infrared spectroscopy, mass spectrometry, elemental analysis, and thermogravimetric analysis (TGA). Complexes 3-7 displayed dimeric molecular structures for all of the complexes with cobalt metal centers interconnected by ??2-O bonding by the alkoxy oxygen atom. TGA and a thermal study of the complexes displayed high volatilities and stabilities for complexes 6 and 7, with sublimation temperatures of 120 ??C/0.5 Torr and 130 ??C/0.5 Torr, respectively

Symptomatic epidural gas cyst treated with epidural block and percutaneous needle aspiration -A case report-

A 68-year-old woman suffered from lower back and radiating pain on her right buttock and posterior calf. Axial magnetic resonance imaging showed a 7 × 7 mm nodular lesion (T1 and, T2 low signal intensity) at the epidural space between the L5-S1 level and computed tomography revealed it was an epidural gas cyst. The authors performed an epidural block and percutaneous needle aspiration of the epidural gas cyst. The patient showed almost complete resolution of symptoms one year later. The authors suggest that an epidural nerve block with needle aspiration of a gas cyst could be an alternative treatment option for patients with a symptomatic epidural gas cyst before surgery

The Expression Patterns of FAM83H and PANX2 Are Associated With Shorter Survival of Clear Cell Renal Cell Carcinoma Patients

FAM83H is primarily known for its role in amelogenesis; however, recent reports suggest FAM83H might be involved in tumorigenesis. Although the studies of FAM83H in kidney cancer are limited, a search of the public database shows a significant association between FAM83H and pannexin-2 (PANX2) in clear cell renal cell carcinomas (CCRCCs). Therefore, we evaluated the clinicopathological significance of the immunohistochemical expression of FAM83H and PANX2 in 199 CCRCC patients. The expression of FAM83H and PANX2 were significantly associated with each other. In univariate analysis, individual, and co-expression pattern of FAM83H and PANX2 was significantly associated with shorter overall survival (OS) and relapse-free survival (RFS) of CCRCC patients: nuclear expression of FAM83H (OS; P < 0.001, RFS; P < 0.001), cytoplasmic expression of FAM83H (OS; P < 0.001, RFS; P < 0.001), nuclear expression of PANX2 (OS; P < 0.001, RFS; P < 0.001), cytoplasmic expression of PANX2 (OS; P < 0.001, RFS; P < 0.001), co-expression pattern of nuclear FAM83H and nuclear PANX2 (OS; P < 0.001, RFS; P < 0.001). In multivariate analysis, nuclear expression of FAM83H (OS; P < 0.001, RFS; P = 0.003) and the co-expression pattern of nuclear FAM83H and PANX2 (OS; P < 0.001, RFS; P < 0.001) were independent indicators of shorter survival of CCRCC patients. Cytoplasmic expression of FAM83H was associated with shorter RFS (P = 0.030) in multivariate analysis. In Caki-1 and Caki-2 CCRCC cells, knock-down of FAM83H decreased PANX2 expression and cell proliferation, and overexpression of FAM83H increased PANX2 expression and cell proliferation. These results suggest that FAM83H and PANX2 might be involved in the progression of CCRCC in a co-operative manner, and their expression might be used as novel prognostic indicators for CCRCC patients

Lack of Toll-like Receptor 4 and 2 Polymorphisms in Korean Patients with Bacteremia

Toll-like receptors (TLRs) are pattern-recognition receptors that are important in innate immune responses to bacterial infection. The purpose of this study is to describe the prevalence of TLRs genetic variations in the bacteremic patients in Korea. A total of 154 patients with bacteremia and 179 healthy volunteers were included. The Asp299Gly and Thr399Ile allele of the TLR4 gene and Arg753Gln and Arg677Trp allele of the TLR2 gene were tested by PCR-RFLP. The DNA sequences were determined to confirm the PCR-RFLP results. Contrary to the expectation, no genetic polymorphisms were detected in both groups of this study, suggesting that it is very rare in Korean

A Prediction Rule to Identify Severe Cases among Adult Patients Hospitalized with Pandemic Influenza A (H1N1) 2009

The purpose of this study was to establish a prediction rule for severe illness in adult patients hospitalized with pandemic influenza A (H1N1) 2009. At the time of initial presentation, the baseline characteristics of those with severe illness (i.e., admission to intensive care unit, mechanical ventilation, or death) were compared to those of patients with non-severe illnesses. A total of 709 adults hospitalized with pandemic influenza A (H1N1) 2009 were included: 75 severe and 634 non-severe cases. The multivariate analysis demonstrated that altered mental status, hypoxia (PaO2/FiO2 ≤ 250), bilateral lung infiltration, and old age (≥ 65 yr) were independent risk factors for severe cases (all P < 0.001). The area under the ROC curve (0.834 [95% CI, 0.778-0.890]) of the number of risk factors were not significantly different with that of APACHE II score (0.840 [95% CI, 0.790-0.891]) (P = 0.496). The presence of ≥ 2 risk factors had a higher sensitivity, specificity, positive predictive value and negative predictive value than an APACHE II score of ≥ 13. As a prediction rule, the presence of ≥ 2 these risk factors is a powerful and easy-to-use predictor of the severity in adult patients hospitalized with pandemic influenza A (H1N1) 2009