Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Protective Role of Transduced Tat-Thioredoxin1 (Trx1) against Oxidative Stress-Induced Neuronal Cell Death via ASK1-MAPK Signal Pathway

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Transduced Tat-aldose Reductase Protects Hippocampal Neuronal Cells against Oxidative Stress-induced Damage

Aldose reductase (AR) protein, a member of the NADPH-dependent aldo-keto reductase family, reduces a wide range of aldehydes and enhances cell survival by inhibition of oxidative stress. Oxidative stress is known as one of the major pathological factor in ischemia. Since the precise function of AR protein in ischemic injury is fully unclear, we examined the function of AR protein in hippocampal neuronal (HT-22) cells and in an animal model of ischemia in this study. Cell permeable Tat-AR protein was produced by fusion of protein transduction domain in Tat for delivery into the cells. Tat-AR protein transduced into HT-22 cells and significantly inhibited cell death and regulated the mitogen-activate protein kinases (MAPKs), Bcl-2, Bax, and Caspase-3 under oxidative stress condition. In an ischemic animal model, Tat-AR protein transduced into the brain tissues through the blood-brain barrier (BBB) and drastically decreased neuronal cell death in hippocampal CA1 region. These results indicate that transduced Tat-AR protein has protective effects against oxidative stress-induced neuronal cell death in vitro and in vivo, suggesting that Tat-AR protein could be used as potential therapeutic agent in ischemic injury.

Fatal Intracranial Hemorrhage in a Patient with Disseminated Intravascular Coagulation associated with Sepsis / 대한구급학회지

In critically ill patients, disseminated intravascular coagulation (DIC) is a common and fatal hematological disorder. DIC is a physiological response to a variety of underlying stimuli that provoke generalized activation of the hemostatic mechanism and is common in septic patients and those with hematological or non-hematological malignant neoplasms. Bleeding is a common clinical feature, and diffuse or multiple-site mucocutaneous bleeding, such as petechia, ecchymosis and hemorrhage from gastrointestinal tract, is often seen. A 58-year-old male was recently diagnosed with intracranial hemorrhage (ICH) caused by DIC associated with sepsis. Mortality of ICH caused by DIC is very high because the underlying condition cannot be quickly treated. Awareness of the possibility of DIC developing in a critically ill patient and the need for immediate initiation of plasma or platelet replacement therapy are important. To the best of our knowledge, this is the first reported case of intracranial hemorrhage in a Korean patient with DIC associated with sepsis.

Fatal Intracranial Hemorrhage in a Patient with Disseminated Intravascular Coagulation associated with Sepsis / 대한중환자의학회지

In critically ill patients, disseminated intravascular coagulation (DIC) is a common and fatal hematological disorder. DIC is a physiological response to a variety of underlying stimuli that provoke generalized activation of the hemostatic mechanism and is common in septic patients and those with hematological or non-hematological malignant neoplasms. Bleeding is a common clinical feature, and diffuse or multiple-site mucocutaneous bleeding, such as petechia, ecchymosis and hemorrhage from gastrointestinal tract, is often seen. A 58-year-old male was recently diagnosed with intracranial hemorrhage (ICH) caused by DIC associated with sepsis. Mortality of ICH caused by DIC is very high because the underlying condition cannot be quickly treated. Awareness of the possibility of DIC developing in a critically ill patient and the need for immediate initiation of plasma or platelet replacement therapy are important. To the best of our knowledge, this is the first reported case of intracranial hemorrhage in a Korean patient with DIC associated with sepsis.

Methazolamide-induced toxic epidermal necrolysis confirmed by lymphocyte activation test

Among various dermatological entities, toxic epidermal necrolysis (TEN) is a rare but potentially fatal delayed hypersensitivity reaction to numerous medications. A 38-year-old male presented with systemic hypersensitivity reaction, such as high fever, pain in the eyes, and diffuse pruritic erythematous maculopapular eruptions with multiple targetoid plaques that became vesicular and bullous. Oral mucosa and conjunctivae were involved. The first sign appeared about 1 week after taking methazolamide (50 mg twice a day) for the management of glaucomatous eyes. Although methazolamide was discontinued, blistering and skin denudation progressed to affect up to 80% of the body surface area and a positive Nikolsky sign was noted. High fever also persisted. Skin lesions started to improve after 2 weeks of management and fever subsided. Cutaneous lesions improved with minimal permanent sequele 2 months later. HLA-B*5901 was found by high-resolution genotyping. The lymphocyte activation test performed 6 months after remission showed a positive response to methazolamide challenge. This is the first case of methazolamide-induced TEN in which methazolamide was confirmed as a culprit drug by the lymphocyte activation test.

Sarcomatoid Intrahepatic Cholangiocarcinoma: A Rare Case of Primary Liver Cancer

Sarcomatoid carcinoma arising from intrahepatic cholangiocyte, an extremely rare primary liver cancer, has highly invasive and metastatic potential. The pathogenesis of this tumor is unclear, although histogenetic mechanisms, such as transdifferentiation/dedifferentiation (epithelial-mesenchymal transition or metaplastic transformation), biphasic differentiation (combination and collision), and redifferentiation, might be suggested to explain the simultaneous co-existence of carcinoma and sarcoma components in the same tumor. Immunohistochemical staining might be necessary to differentiate whether sarcomatous component is originated from hepatocyte or cholangiocyte. We report a case of sarcomatoid intrahepatic cholangiocarcinoma in a 58 year-old man presenting as an incidentally detected liver mass on regular health examination, which was diagnosed by an application of immunohistochemical methods after surgical resection, with a review of the literature based on 9 cases reported in Korea.

Pulmonary Pneumatocele in a Pneumonia Patient Infected with Extended-Spectrum beta-Lactamase Producing Proteus mirabilis / 결핵및호흡기질환

Pulmonary pneumatoceles are air-filled thin-walled spaces within the lung and are rare in adult cases of pneumonia. We report the case of a 74-year-old male who was admitted with a cough and sputum production. He had been treated with oral dexamethasone since a brain tumorectomy 6 months prior. Contrast-enhanced computed tomography (CT) of the chest revealed a large pneumatocele in the right middle lobe and peripheral pneumonic consolidation. Bronchoalveolar lavage was performed; cultures identified extended-spectrum beta-lactamase (ESBL) producing Proteus mirabilis. A 4-week course of intravenous ertapenem was administered, and the pneumatocele with pneumonia resolved on follow-up chest CT. To the best of our knowledge, this is the first reported case of pulmonary pneumatocele caused by ESBL-producing P. mirabilis associated with pneumonia.

Retraction: Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury

No abstract available.

Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury

Reactive oxygen species (ROS) contribute to the development of a number of neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an important role in transcriptional regulation, acting as molecular chaperone and antioxidant. In the present study, we investigated whether DJ-1 protein shows a protective effect against oxidative stress-induced neuronal cell death in vitro and in ischemic animal models in vivo. To explore DJ-1 protein's potential role in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1 fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a dose- and time-dependent manner. Transduced Tat-DJ-1 protein increased cell survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation induced by H2O2. Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ-1 protein prevented neuronal cell death induced by transient forebrain ischemia in the CA1 region of the hippocampus. These results demonstrate that transduced Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for ischemic injuries related to oxidative stress.

Partial Penetrating Allografts of Rabbit Corneas Stored in M-K Medium

Each three rabbit corneas were stored in McCarey-Kaufman medium at 4 degrees C for 5, 9 and 14 days and used as donor materials in 6mm partial penetrating corneal allografts. These results were compared to that group of penetrating keratoplasties with corneas stored conventional moist chamber at 4 degrees C for 5 days. All the M-K media stored corneas for 5 and 9 days were in clear graft after keratoplasty during the observation period of 6 months but the corneas stored for 14 days were developed eventvally irreversilde opaque after grafts. At 6 months after keratoplasties allthe rabbits eyes were enucleated and sectioned for histopathologic study of endothelia with the light and electron microscopes. Endothelia of the corneas stored for 5 and 9 days showed rarely endothelial degenerative changes. But the corneas stored up to 14 days showed significant changes including of disappearanee of most endothelial membranes and cytoplasms in light microscopies and swelling of nucleus, dispersed chromatin clump, multiple small and large vacuoles in cytoplasm and occasional autolysis of cytoplasm were observed in electron microscopies.