Adipsic Hypernatremia after Clipping of a Ruptured Aneurysm in the Anterior Communicating Artery:A Case Report

Adipsia is a rare disorder that occurs due to damage to the osmoreceptor and not feeling thirst despite hyperosmolality. Adipsic hypernatremia can occur when there is damage to the anterior communicating artery that supplies blood to osmoreceptors, and the level of arginine vasopressin secretion varies widely. A 37-year-old woman, suffering from severe headache, was consulted to the nephrology department for hypernatremia and polyuria after clipping of a ruptured aneurysm in the anterior communicating artery. Despite her hypernatremic hyperosmolar state, she denied thirst and did not drink spontaneously. She was diagnosed adipsic hypernatremia by evaluating the osmoregulatory and baroregulatory function tests.Because adipsic hypernatremia is caused by not enough drinking water even for hyperosmolality due to the lack of thirst stimulus, the strategies of treatment are that setting the target body weight when serum osmolality is normal and have the patient drink water until patient reach the target body weight. Adipsic hypernatremia should be considered to be a rare complication of subarachnoid hemorrhage associated with an anterior communicating artery aneurysm.

Hepatopulmonary Syndrome with Finger Clubbing / 대한내과학회지

Hepatopulmonary syndrome is a rare lung complication of liver cirrhosis, caused by pulmonary microvascular vasodilation that induces abnormal arterial oxygenation. Typical findings on physical examination are finger clubbing and cyanosis. Dyspnea is a common symptom and is worse in the upright position. Contrast echocardiography is a useful diagnostic test. Currently, the only effective treatment is liver transplantation. We report the case of a woman with cirrhosis who has hepatopulmonary syndrome with finger clubbing, confirmed by contrast echocardiography. The patient is waiting for a liver transplant.

SP-8356, a (1S)-(-)-Verbenone Derivative, Inhibits the Growth and Motility of Liver Cancer Cells by Regulating NF-κB and ERK Signaling

Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.

SP-8356, a (1S)-(-)-Verbenone Derivative, Inhibits the Growth and Motility of Liver Cancer Cells by Regulating NF-κB and ERK Signaling

Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.

Hepatopulmonary Syndrome with Finger Clubbing / 대한내과학회지

Hepatopulmonary syndrome is a rare lung complication of liver cirrhosis, caused by pulmonary microvascular vasodilation that induces abnormal arterial oxygenation. Typical findings on physical examination are finger clubbing and cyanosis. Dyspnea is a common symptom and is worse in the upright position. Contrast echocardiography is a useful diagnostic test. Currently, the only effective treatment is liver transplantation. We report the case of a woman with cirrhosis who has hepatopulmonary syndrome with finger clubbing, confirmed by contrast echocardiography. The patient is waiting for a liver transplant.

Contrast-Induced Acute Kidney Injury after Coil Embolization for Aneurysmal Subarachnoid Hemorrhage

PURPOSE: Contrast-induced acute kidney injury (CI-AKI) is associated with poor outcomes after percutaneous coronary intervention. However, CI-AKI has rarely been evaluated within the neurovascular field. The aim of this study was to investigate the incidence and clinical implication of CI-AKI after coil embolization in patients with an aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: Between January 2005 and March 2016, 192 patients who underwent coil embolization were enrolled in this study. CI-AKI was defined as an increase from baseline serum creatinine concentration of >25% or >0.5 mg/dL within 72 hours after coil embolization. A poor clinical outcome was defined as a score of ≥3 on the modified Rankin Scale at one-year post-treatment. RESULTS: A total of 16 patients (8.3%) died as a result of medical problems within one year. CI-AKI was identified in 14 patients (7.3%). Prominent risk factors for one-year mortality included CI-AKI [odds ratio (OR): 16.856; 95% confidence interval (CI): 3.437–82.664] and an initial Glasgow Coma Scale (GCS) score ≤8 (OR: 5.565; 95% CI: 1.703–18.184). A poor clinical outcome was associated with old age (≥65 years) (OR: 7.921; 95% CI: 2.977–21.076), CI-AKI (OR: 11.281; 95% CI: 2.138–59.525), an initial GCS score ≤8 (OR 31.02; 95% CI, 10.669–90.187), and a ruptured aneurysm (p=0.016, OR: 4.278) in posterior circulation. CONCLUSION: CI-AKI seems to be an independent predictor of the overall outcomes of aSAH after endovascular treatment.

Bipolar Disorder Associated microRNA, miR-1908-5p, Regulates the Expression of Genes Functioning in Neuronal Glutamatergic Synapses

Bipolar disorder (BD), characterized by recurrent mood swings between depression and mania, is a highly heritable and devastating mental illness with poorly defined pathophysiology. Recent genome-wide molecular genetic studies have identified several protein-coding genes and microRNAs (miRNAs) significantly associated with BD. Notably, some of the proteins expressed from BD-associated genes function in neuronal synapses, suggesting that abnormalities in synaptic function could be one of the key pathogenic mechanisms of BD. In contrast, however, the role of BD-associated miRNAs in disease pathogenesis remains largely unknown, mainly because of a lack of understanding about their target mRNAs and pathways in neurons. To address this problem, in this study, we focused on a recently identified BD-associated but uncharacterized miRNA, miR-1908-5p. We identified and validated its novel target genes including DLGAP4, GRIN1, STX1A, CLSTN1 and GRM4, which all function in neuronal glutamatergic synapses. Moreover, bioinformatic analyses of human brain expression profiles revealed that the expression levels of miR-1908-5p and its synaptic target genes show an inverse-correlation in many brain regions. In our preliminary experiments, the expression of miR-1908-5p was increased after chronic treatment with valproate but not lithium in control human neural progenitor cells. In contrast, it was decreased by valproate in neural progenitor cells derived from dermal fibroblasts of a BD subject. Together, our results provide new insights into the potential role of miR-1908-5p in the pathogenesis of BD and also propose a hypothesis that neuronal synapses could be a key converging pathway of some BD-associated protein-coding genes and miRNAs.

Simvastatin Reduces Lipopolysaccharides-Accelerated Cerebral Ischemic Injury via Inhibition of Nuclear Factor-kappa B Activity

Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusion-evoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-1beta in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-kappaB, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of IkappaB. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.

Amelioration of Cerebral Ischemic Injury by a Synthetic Seco-nucleoside LMT497

Recently, we reported that the A3 adenosine receptor (A3AR) agonist LJ529 (2-chloro-N6-(3-iodobnzyl)-5'-N-methylcarbamoyl-4'-thioadenosine) reduces cerebral ischemic injury via inhibition of recruitment of peripheral inflammatory cells into ischemic brain lesion. A3AR agonists, however, are known to possess anti-platelet activity, which may deter the combination therapy with tissue plasminogen activator for the therapy of cerebral ischemic stroke. Thus, the present study investigates the neuroprotective/anti-ischemic effect of a synthetic seco-nucleoside, LMT497 ((S)-2-((R)-1-(2-chloro-6-(3-iodobenzylamino)-9H-purin-9-yl)-2-hydroxyethoxy)-3-hydroxy-N-methylpropanamide) with little anti-platelet activity. LMT497 neither showed A3AR binding activity nor anti-platelet activity. In our present study LMT497 significantly attenuated the injury/death of cortical neurons exposed to oxygen-glucose deprivation (OGD) followed by re-oxygenation (R). LMT497 significantly reduced the ascending cellular level of reactive oxygen species under ischemic conditions by increasing the superoxide dismutase (SOD) levels. LMT497 also inhibited the migration of microglia which mediates inflammatory responses in ischemia. In rats subjected to middle cerebral artery occlusion (MCAO, 1.5 h) followed by reperfusion, LMT497 largely reduced brain infarction volume, and edema, and improved neurological score. Therapeutic efficacy of LMT497 was obtained by twice treatments even at 10 h and 18 h after the onset of ischemia. Collectively, LMT497 could be a therapeutic drug candidate with a wide therapeutic time window for the treatment of cerebral ischemic stroke.

4-hydroxy-2(E)-Nonenal facilitates NMDA-Induced Neurotoxicity via Triggering Mitochondrial Permeability Transition Pore Opening and Mitochondrial Calcium Overload

N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity is one of the major causes for neuronal cell death during cerebral ischemic insult. Previously, we reported that the final product of lipid membrane peroxidation 4-hydroxy-2E-nonenal (HNE) synergistically increased NMDA receptor-mediated excitotoxicity (J Neurochem., 2006). In this study, we investigated the mechanism involved in the synergistic neuronal cell death induced by co-treatment with HNE and NMDA. Although neither HNE (1 microM) nor NMDA (2 microM) alone induced the death of cortical neurons, simultaneous treatment of neuronal cells with HNE and NMDA synergistically evoked the death of the cells. However, the synergistic effect on neuronal death was observed only in the presence of calcium. HNE neither increased the cytosolic calcium level ([Ca2+]i) nor altered the NMDA-induced intracellular calcium influx. However, HNE together with NMDA elevated the mitochondrial calcium level and depolarized the mitochondrial transmembrane potential. Furthermore, HNE evoked damage of isolated mitochondria at the cytosolic calcium level (200 nM), which is maximally induced by 2 microM NMDA. Consistently, ATP was depleted in neurons when treated with both HNE and NMDA together. Ciclopirox, a potent inhibitor of mitochondrial permeability transition pore opening (Br. J. Pharmacol., 2005), largely prevented the synergistic damage of mitochondria and death of cortical neurons. Therefore, although low concentrations of HNE and NMDA cannot individually induce neuronal cell death, they can evoke the neuronal cell death by synergistically accelerating mitochondrial dysfunction.

Role of TGF-beta in Survival of Phagocytizing Microglia: Autocrine Suppression of TNF-alpha Production and Oxidative Stress

Microglia are recognized as residential macrophageal cells in the brain. Activated microglia play a critical role in removal of dead or damaged cells through phagocytosis activity. During phagocytosis, however, microglia should survive under the harmful condition of self-producing ROS and pro-inflammatory mediators. TGF-beta has been known as a classic anti-inflammatory cytokine and controls both initiation and resolution of inflammation by counter-acting inflammatory cytokines. In the present study, to understand the self-protective mechanism, we studied time-dependent change of TNF-alpha and TGF-beta production in microglia phagocytizing opsonized-beads (i.e., polystyrene microspheres). We found that microglia phagocytized opsonized-bead in a time-dependent manner and simultaneously produced both TNF-alpha and TGF-beta. However, while TNF-alpha production gradually decreased after 6 h, TGF-beta production remained at increased level. Microglial cells pre-treated with lipopolysaccharides (a strong immunostimulant, LPS) synergistically increased the production of TNF-alpha and TGF-beta both. However, LPS-pretreated microglia produced TNF-alpha in a more sustained manner and became more vulnerable, probably due to the marked and sustained production of TNF-alpha and reduced TGF-beta. Intracellular oxidative stress appears to change in parallel with the microglial production of TNF-alpha. These results indicate TGF-beta contributes for the survival of phagocytizing microglia through autocrine suppression of TNF-alpha production and oxidative stress.

Calcifying epithelial odontogenic tumor associated with the left mandibular first premolar: a case report and literature review

Calcifying epithelial odontogenic tumor (CEOT) is a rarely reported benign tumor, accounting for 0.4-3% of all odontogenic tumors. Approximately 150 cases have been reported in the literature between 1958 and 2003. The age range of CEOT varies from 8 to 92 years with mean of 36.9 years, and the occurrence of the lesion in both genders is almost equal. It has 2 clinico-topographic variants: the intraosseous (94%) and the extraosseous (6%) type. The intraosseous type has a predilection for mandible (maxilla : mandible ratio of 1 : 2). The intraosseous CEOT commonly associated with non-erupted teeth accounts for more than half (52%) of the cases and usually appears as painless swelling that causes bony expansion. The location of diffused round-shaped calcifying material is inside the connective tissue stroma and epithelial islands. The tumors tend to be located toward the tooth crown, which usually has a unilocular radiolucent region containing variant radiopaque materials radiologically. In this paper, we report a case of CEOT occurring in the left mandibular first premolar of a 23-year-old female and present a brief review of the literature.

Study on bone healing process following cyst enucleation using fractal analysis

INTRODUCTION: Bone regeneration of cystic defects of the jaws after a cyst treatment requires lengthy healing periods. Generally, the bony changes are observed periodically through a visual radiographic reading as well as by the clinical opinion and radiographic images (panorama, periapical view), but it is difficult to compare the objective bony changes using only the radiographic density. In addition, it is difficult to observe minute bony changes through a visual radiographic reading, which can lead to a subjective judgment. This study exmined the bone density after the enucleation of a jaw cyst by fractal analysis. MATERIALS AND METHODS: Eighteen patients with a cystic lesion on the jaw were assessed. Panoramic radiographs were taken preoperatively, immediately postoperatively, and 1, 3, 6 and 12 months after cyst enucleation. The images were analyzed by fractal analysis. RESULTS: The mean fractal dimensions increased immediately after surgery and 3, 6 and 12 months postoperatively. The postoperative 6 and 12 months fractal dimension was similar to the controls. CONCLUSION: Fractal analysis was used to overcome the limit of a subjective reading during an assessment of bone regeneration after cyst enucleation.

Effect on complications associated with its position and angulation following mandibular third molar extraction

INTRODUCTION: Mandibular third molar extraction is one of the most common procedures performed in oral and maxillofacial surgery units. Although the overall complication rate is low with most complications being minor, mandibular third molar removal is so common that the population morbidity of complications might be significant. Therefore, efforts to limit intraoperative or postoperative complications might have a significant impact in terms of enhancing the patient outcome. The aims of this study were to identify the position and angulation associated complications after mandibular third molar extractions. MATERIALS AND METHODS: This study surveyed 568 patients who had a mandibular third molar extracted, showed clinical complications and underwent a radiographic measurement of the available space, depth and spatial relationship. RESULTS: The results obtained were as follows: 1. The complications were a dry socket, nerve injury, root rest, infection, bleeding, hamatoma, and adjacent teeth injury. 2. There were no significant differences between the complication and ramus relationship (available space) of the mandibular third molar. 3. There were no significant differences between the complications and depth of the mandibular third molar. 4. There were no significant differences between the complications and spatial relationship of the mandibular third molar. CONCLUSION: There were no significant differences in the complication rate, ramus relationship, depth and spatial relationship of the mandibular third molar. This suggests that the position and angulation of the mandibular third molar may not have an impact on the complications. The relationship between the position and angulation of the mandibular third molar, and complications deserves a further study using longitudinal data.

Etoposide Reduces Peroxynitrite-Induced Cytotoxicity via Direct Scavenging Effect

Previously, we reported that glucose-deprived astrocytes are more vulnerable to the cytotoxicity of peroxynitrite, the reaction product of nitric oxide and superoxide anion. The augmented vulnerability of glucose-deprived astrocytes to peroxynitrite cytotoxicity was dependent on their proliferation rate. Inhibition of cell cycle progression has been shown to inhibit the apoptotic cell death occurring in cerebral ischemia-reperfusion. In the present study, we demonstrate that the increased death of glucose-deprived astrocytes by peroxynitrte was largely blocked by the cell cycle phase G2/M transition blocker etoposide. However, the cytoprotective effect of etoposide was not associated with its inhibition of cell cycle progression. Instead, etoposide effectively scavenged peroxynitrite. However, etoposide did not scavenge individual nitric oxide and superoxide anion and it did not prevent the hydrogen peroxide-induced cytotoxicity. The present results indicate that etoposide prevents the toxicity of peroxynitrite in astrocytes by directly scavenging peroxynitrite, not by inhibiting cell cycle progression.

Two Species of Penicillium Associated with Blue Mold of Yam in Korea

During 2007 survey of post-harvest diseases of yam performed in May and June, severe tuber loss caused by blue mold was observed in Iksan, Cheonbuk Province. Two species of Penicillium were isolated from the infected tubers. Based on beta-tubulin gene sequence analysis, and cultural and morphological characteristics, the isolates were identified as Penicillium sclerotigenum and P. polonicum. P. sclerotigenum, which is a novel to Korea, is presently described and illustrated.

Six Species of Penicillium Associated with Blue Mold of Grape

Grape fruits with blue mold symptoms were collected from house storages in different locations in Korea and were investigated for their association with Penicillium species. A total of 12 isolates of Penicillium were isolated from the collected fruits. Based on morphological and cultural characteristics and beta-tublin gene sequence data analysis, they were identified as P. bialowiezense, P. citrinum, P. echinulatum, P. expansum, P. solitum and unidentified Penicillium species. P. solitum was the predominant followed by P. expansum. P. bialowiezense and P. echinulatum were newly recorded in Korea. beta-Tubulin gene sequences could be used to distinguish each species of Penicillium and the molecular groups were correlated well with the morphological species. The unidentified species was supposed to be a new species, not previously reported in literature.

Two New Records of Penicillium Associated with Blue Moldy Bulbs of Lily in Korea

Two new records of Penicillium from blue moldy bulbs of lily are reported in Korea. The Korean isolates of P. albocoremium (Frisvad) Frisvad and P. tulipae Overy and Frisvad were phylogenetically identical to the reference species based on DNA sequence of the beta-tubulin gene. P. albocoremium and P. tulipae are described and illustrated.

Diversity of Endophytic Fungi Associated with Taraxacum coreanum and Their Antifungal Activity

Endophytic fungi were isolated from healthy leaf and root samples of Taraxacum coreanum. Of the 72 isolates recovered, 39 were from leaves and 33 from roots with an isolation frequency of 54% and 46%, respectively. Based on ITS sequence analysis, 72 isolates were classified into 19 genera of which 17 were under the phylum Ascomycota and 2 were under Basidiomycota. Diverse genera were found and Alternaria, Cladosporium, Fusarium and Phoma were dominant. Out of 19 genera, Apodus, Ceriporia, Dothideales, Leptodontidium, Nemania, Neoplaconema, Phaeosphaeria, Plectosphaerella and Terfezia were new to Korea. Seventy two isolates were screened for antifungal activity, of which 10 isolates (14%) were found active at least against one of the tested fungi. Isolate 050603 had the widest antifungal spectra of activity, and isolates 050592 and 050611 were active against three plant pathogenic fungi.

The inhibitory effect of opioid on the hyperpolarization-activated cation currents in rat substantia gelatinosa neurons

The action of opioid on the hyperpolarization-activated cation current (Ih) in substantia gelatinosa neurons were investigated by using whole-cell voltage-clamp recording in rat spinal brain slices. Hyperpolarizing voltage steps revealed slowly activating currents in a subgroup of neurons. The half-maximal activation and the reversal potential of the current were compatible to neuronal Ih. DAMGO (1 muM), a selective-opioid agonist, reduced the amplitude of Ih reversibly. This reduction was dose-dependent and was blocked by CTOP (2 muM), a selective mu-opioid antagonist. DAMGO shifted the voltage dependence of activation to more hyperpolarized potential. Cesium (1 mM) or ZD 7288 (100 muM) blocked Ih and the currents inhibited by cesium, ZD 7288 and DAMGO shared a similar time and voltage dependence. These results suggest that activation of mu-opioid receptor by DAMGO can inhibit Ih in a subgroup of rat substantia gelatinosa neurons.