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

Efficacy of endoscopic third ventriculostomy in old aged patients with normal pressure hydrocephalus

Normal pressure hydrocephalus (NPH) is a chronic disorder caused by interrupted CSF absorption or flow. Generally, shunt placement is first option for NPH treatment. Due to complications of ventriculo-peritoneal (VP) shunt placement, endoscopic third ventriculostomy (ETV) can be considered as an alternative treatment option. Here we report the efficacy of ETV especially in old aged patients with normal pressure hydrocephalus. Total 21 old aged patients with communicating hydrocephalus with opening pressure, measured via lumbar puncture, less than 20cm H2O underwent ETV. 15 patients had primary/idiopathic NPH and 6 patients had secondary NPH. All patients were studied with a MRI to observe the flow void at aqueduct and the fourth ventricle outflow. And all of them underwent ETV. In a group with peak velocity was higher than 5cm/s, nine patients (75%) were evaluated was ‘favorable’ and three of them (25%) was scored ‘poor’. In another group with peak velocity less than 5cm/s, three of them were scored ‘poor’ and two of them were scored ‘stable’. None of them was evaluated as ‘favorable’. We also evaluated the outcomes according to etiology: 12 patients (80% of the patients with primary NPH) were evaluated with ‘favorable’ after ETV treatment. Two patients (13.3%) were as ‘stable’. And one patient was as ‘poor’ evaluated. Five patients (83.3%) among patients with secondary NPH were as ‘poor’ evaluated and one of them was stable and no patient was as ‘favorable’ evaluated. 4 patients, which was as ‘poor’ evaluated in the group with the secondary NPH, underwent additional VP shunt implantation. Overall, the outcomes of the group with the idiopathic NPH after ETV treatment were more favorable than of the group with the secondary NPH. Our study suggest that ETV can be effective for selected elderly patients with primary/idiopathic NPH, when they satisfy criteria including positive aqueduct flow void on T2 Sagittal MRI and the aqueductal peak velocity, which is greater than 5cm/s on cine MRI

Reversible Lansoprazole-Induced Interstitial Lung Disease Showing Improvement after Drug Cessation

Lansoprazole is an acid proton-pump inhibiting drug that is used for the treatment of duodenal or gastric ulcers, H. pylori infection, gastroesophageal reflux disease or Zollinger-Ellison syndrome. Although lansoprazole is well known for its gastrointestinal and dermatologic adverse effects, mild pulmonary symptoms are also known to develop from taking this drug. There have been no reports about lansoprazole-induced interstitial lung disease. We report here a case of lansoprazole-induced interstitial lung disease that developed in a 66-year-old man

Congenital Cavernous Sinus Cystic Teratoma

Teratomas represent 0.5% of all intracranial tumors. These benign tumors contain tissue representative of the three germinal layers. Most teratomas are midline tumors located predominantly in the sellar and pineal regions. The presence of a teratoma in the cavernous sinus is very rare. Congenital teratomas are also rare, especially those of a cystic nature. To our knowledge, this would be the first case report of a congenital, rapidly growing cystic teratoma within the cavernous sinus. A three-month-old boy presented with a past medical history of easy irritability and poor oral intake. A magnetic resonance image (MRI) scan of the head disclosed a large expanding cystic tumor filling the right cavernous sinus and extending into the pterygopalatine fossa through the foramen rotundum. These scans also demonstrated a small area of mixed signal intensity, the result of the different tissue types conforming to the tumor. Heterogeneous enhancement was seen after the infusion of contrast medium. However, this was a cystic tumor with a large cystic portion. Thus, a presumptive diagnosis of cystic glioma was made. With the use of a right frontotemporal approach, extradural dissection of the tumor was performed. The lesion entirely occupied the cavernous sinus, medially displacing the Gasserian ganglion and trigeminal branches (predominantly V1 and V2). The lesion was composed of different tissues, including fat, muscle and mature, brain-like tissue. The tumor was completely removed, and the pathological report confirmed the diagnosis of a mature teratoma. There was no evidence of recurrence. Despite the location of the lesion in the cavernous sinus, total removal can be achieved with the use of standard microsurgical techniques

Primary Adenosquamous Cell Carcinoma of the Pancreas: A Case Report with a Review of the Korean Literature

The most common pancreatic cancer is adenocarcinoma. Primary adenosquamous cell carcinoma of the pancreas is very rare and aggressive. A 46-year-old man presented with a 3-month history of dyspepsia and a 7-kg weight loss. The physical examination showed tenderness of the right upper quadrant of the abdomen. There was no jaundice. Amylase and lipase were elevated. CA 19-9 was elevated to 566.7 U/mL. Gastroduodenoscopy showed a hard ulceroinfiltrative mass with a yellowish exudate that bled readily on touch in the second portion of the duodenum. Abdominal computed tomography showed a 7.1 × 6.3-cm heterogeneously enhancing mass in the pancreatic head. The pancreatic mass had invaded the duodenum wall, gastric antrum, and gastroduodenal artery sheath. Fine-needle aspiration biopsy of the pancreatic mass revealed adenosquamous cell carcinoma, anaplastic type. We concluded that an adenosquamous cell carcinoma of pancreas had invaded the duodenal mucosa causing ulceration

Infectious Mononucleosis Hepatitis in Young Adults: Two Case Reports

Infectious mononucleosis due to Epstein-Barr virus (EBV) infection sometimes causes acute hepatitis, which is usually self-limiting with mildly elevated transaminases, but rarely with jaundice. Primary EBV infection in children is usually asymptomatic, but in a small number of healthy individuals, typically young adults, EBV infection results in a clinical syndrome of infectious mononucleosis with hepatitis, with typical symptoms of fever, pharyngitis, lymphadenopathy, and hepatosplenomegaly. EBV is rather uncommonly confirmed as an etiologic agent of acute hepatitis in adults. Here, we report two cases: the first case with acute hepatitis secondary to infectious mononucleosis and a second case, with acute hepatitis secondary to infectious mononucleosis concomitantly infected with hepatitis A. Both cases involved young adults presenting with fever, pharyngitis, lymphadenopathy, hepatosplenomegaly, and atypical lymphocytosis confirmed by serologic tests, liver biopsy and electron microscopic study

The Utility of Multi-detector Row Spiral CT for Detection of Coronary Artery Stenoses

Contrast-enhanced multi-detector row spiral computed tomography (MDCT) was introduced as a promising noninvasive method for vascular imaging. This study examined the accuracy of this technique for detecting significant coronary artery stenoses. Both MDCT(Sensation 16, Siemens, Germany, 12 × 0.75 mm collimation and 0.42 sec rotation speed, 120 kV, 500 effective mA, and 2.7 mm/rotation table-feed) and invasive coronary angiography (CAG) were performed on 61 patients (mean age 59.2 ± 10, 44 men) who were suspected of having coronary artery disease. All patients were treated with atenolol (25 - 50 mg) prior to imaging and the heart rate was maintained below 65 beats per minutes during image acquisition. The images were reconstructed in the diastole around TI - 400 ms with a 0.5 mm increment and a 1.0 mm thickness. All coronary arteries with a diameter of 2.0 mm or more were assessed for the presence of a stenosis (> 50% luminal narrowing). Two independent radiologists who were unaware of the results of the invasive CAG evaluated the MDCT data, and the results were compared with those from the invasive CAG (interval 1- 27, mean 11 days). An evaluation of the CT coronary angiogram (CTCA) was possible in 58 of the 61 patients (95%). Image acquisition of the major coronary arteries including the left main trunk was available in 229 out of 244 arteries. Invasive CAG showed that 35 out of 58 patients had significant coronary artery stenoses by. patient analysis of those who could be evaluated showed that CT coronary angiography correctly classified 30 out of 35 patients as having at least 1 coronary stenosis (sensitivity 85.7%, specificity 91.3%, positive predictive value 93.8%, negative predictive value 80.8%). By analyzing each coronary artery, CAG found 62 stenotic coronary arteries in the 229 coronary arteries that could be evaluated. MDCT correctly detected 50 out of 62 stenotic coronary arteries and an absence of stenosis was correctly identified in 156 out of 167 normal coronary arteries (sensitivity 80.6%, specificity 93.4%, positive predictive value 81.9%, negative predictive value 92.8%). The non-invasive technique of MDCT for examining the coronary artery appears to be a useful method for detecting coronary artery stenoses with a high accuracy particularly with the proximal portion and large arteries