Effect of Pioglitazone on Perihematomal Edema in Intracerebral Hemorrhage Mouse Model by Regulating NLRP3 Expression and Energy Metabolism

Objective@#: Cerebral edema is the predominant mechanism of secondary inflammation after intracerebral hemorrhage (ICH). Pioglitazone, peroxisome proliferator-activated receptor gamma agonist has been shown to play a role in regulation of central nervous system inflammation. Here, we examined the pharmacological effects of pioglitazone in an ICH mouse model and investigated its regulation on NLRP3 inflammasome and glucose metabolism. @*Methods@#: The ICH model was established in C57 BL/6 mice by the stereotactical inoculation of blood (30 µL) into the right frontal lobe. The treatment group was administered i.p. pioglitazone (20 mg/kg) for 1, 3, and 6 days. The control group was administered i.p. phosphate-buffered saline for 1, 3, and 6 days. We investigated brain water contents, NLRP3 expression, and changes in the metabolites in the ICH model using liquid chromatography-tandem mass spectrometry. @*Results@#: On day 3, brain edema in the mice treated with pioglitazone was decreased more than that in the control group. Expression levels of NLRP3 in the ICH model treated with pioglitazone were decreased more than those of the control mice on days 3 and 7. The pioglitazone group showed higher levels of glycolytic metabolites than those in the ICH mice. Lactate production was increased in the ICH mice treated with pioglitazone. @*Conclusion@#: Our results demonstrated less brain swelling following ICH in mice treated with pioglitazone. Pioglitazone decreased NLRP3-related brain edema and increased anaerobic glycolysis, resulting in the production of lactate in the ICH mice model. NLRP3 might be a therapeutic target for ICH recovery.

Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy

Background@#Ceramides are associated with metabolic complications including diabetic nephropathy in patients with diabetes.Recent studies have reported that podocytes play a pivotal role in the progression of diabetic nephropathy. Also, mitochondrial dysfunction is known to be an early event in podocyte injury. Thus, we tested the hypothesis that ceramide accumulation in podocytes induces mitochondrial damage through reactive oxygen species (ROS) production in patients with diabetic nephropathy. @*Methods@#We used Otsuka Long Evans Tokushima Fatty (OLETF) rats and high-fat diet (HFD)-fed mice. We fed the animals either a control- or a myriocin-containing diet to evaluate the effects of the ceramide. Also, we assessed the effects of ceramide on intracellular ROS generation and on podocyte autophagy in cultured podocytes. @*Results@#OLETF rats and HFD-fed mice showed albuminuria, histologic features of diabetic nephropathy, and podocyte injury, whereas myriocin treatment effectively treated these abnormalities. Cultured podocytes exposed to agents predicted to be risk factors (high glucose, high free fatty acid, and angiotensin II in combination [GFA]) showed an increase in ceramide accumulation and ROS generation in podocyte mitochondria. Pretreatment with myriocin reversed GFA-induced mitochondrial ROS generation and prevented cell death. Myriocin-pretreated cells were protected from GFA-induced disruption of mitochondrial integrity. @*Conclusion@#We showed that mitochondrial ceramide accumulation may result in podocyte damage through ROS production.Therefore, this signaling pathway could become a pharmacological target to abate the development of diabetic kidney disease.

The Use of the Bethesda System for Reporting Thyroid Cytopathology in Korea: A Nationwide Multicenter Survey by the Korean Society of Endocrine Pathologists

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has standardized the reporting of thyroid cytology specimens. The objective of the current study was to evaluate the nationwide usage of TBSRTC and assess the malignancy rates in each category of TBSRTC in Korea. METHODS: Questionnaire surveys were used for data collection on the fine needle aspiration (FNA) of thyroid nodules at 74 institutes in 2012. The incidences and follow-up malignancy rates of each category diagnosed from January to December, 2011, in each institute were also collected and analyzed. RESULTS: Sixty out of 74 institutes answering the surveys reported the results of thyroid FNA in accordance with TBSRTC. The average malignancy rates for resected cases in 15 institutes were as follows: nondiagnostic, 45.6%; benign, 16.5%; atypical of undetermined significance, 68.8%; suspicious for follicular neoplasm (SFN), 30.2%; suspicious for malignancy, 97.5%; malignancy, 99.7%. CONCLUSIONS: More than 80% of Korean institutes were using TBSRTC as of 2012. All malignancy rates other than the SFN and malignancy categories were higher than those reported by other countries. Therefore, the guidelines for treating patients with thyroid nodules in Korea should be revisited based on the malignancy rates reported in this study.

Benefits of Thromboelastography and Thrombin Generation Assay for Bleeding Prediction in Patients With Thrombocytopenia or Hematologic Malignancies

BACKGROUND: Thromboelastography (TEG) provides comprehensive information on the whole blood clot formation phases, whereas thrombin generation assay (TGA) reveals the endogenous thrombin levels in plasma. We investigated the potential significance of TEG and TGA parameters for prediction of clinical bleeding in hematologic patients on the basis of the patient's platelet levels. METHODS: TEG and TGA were performed in 126 patients with thrombocytopenia or hematologic malignancies. The bleeding tendencies were stratified on the basis of the World Health Organization bleeding grade. RESULTS: Maximum amplitude (MA) and clot formation in TEG and endogenous thrombin potential (ETP) in TGA showed significant associations with high bleeding grades (P=0.001 and P=0.011, respectively). In patients with platelet counts ≤10×10⁹/L, low MA values were strongly associated with a high bleeding risk. For bleeding prediction, the area under the curve (AUC) of MA (0.857) and ETP (0.809) in patients with severe thrombocytopenia tended to be higher than that of platelets (0.740) in all patients. Patients with platelet counts ≤10×10⁹/L displayed the highest AUC of the combined MA and ETP (0.929). CONCLUSIONS: Both TEG and TGA were considered to be good predictors of clinical bleeding in patients with severe thrombocytopenia. Combination of the ETP and MA values resulted in a more sensitive bleeding risk prediction in those with severe thrombocytopenia.

High-dose tenofovir is not effective in suppressing hepatitis B virus replication in patients with hepatocellular carcinoma progression: a preliminary result

BACKGROUNDS/AIMS: Nucleos(t)ide analogues (NUCs) effectively suppress hepatitis B virus (HBV) replication, but hepatocellular carcinoma (HCC) recurrence often leads to HBV replication despite NUC therapy. The aim of this study was to determine whether high-dose tenofovir (TNF) therapy can suppresses HCC recurrence-associated HBV replication. METHODS: We performed a single-arm prospective study to assess the clinical feasibility of high-dose TNF (hdTNF). We recruited 10 patients during September 2015 and followed up for 3 months or early drop-out. RESULTS: All 10 patients had HCC of advanced stages due to HCC recurrence and gradual progression. The average age of patients was 51.2+/-4.7 years and 9 were male. Three patients did not tolerate the increased TNF dosage and were dropped out early. The other 7 patients were relatively tolerable to the increased dosage of TNF 5 tablets per day. One patient had mild gastrointestinal symptoms and another patient complained of insomnia. Increased HBV replication and HCC progression was observed despite hdTNF for 4-8 weeks. All 7 patients showed tumor progression during the 3 month follow-up. In these patients, blood HBV DNA before hdTNF was 50-200 copies/ml; and 4-8 weeks after hdTNF, the HBV replication status was not improved with blood HBV DNA of 50-300 copies/ml. This clinical study was terminated early after these negative results were confirmed. CONCLUSIONS: The results of this study indicated that high dose of TNF up to 5-fold the recommended dosage is not tolerated by a considerable proportion of patients and also ineffective in suppressing HCC progression-associated HBV replication.

Understanding Metabolomics in Biomedical Research

The term "omics" refers to any type of specific study that provides collective information on a biological system. Representative omics includes genomics, proteomics, and metabolomics, and new omics is constantly being added, such as lipidomics or glycomics. Each omics technique is crucial to the understanding of various biological systems and complements the information provided by the other approaches. The main strengths of metabolomics are that metabolites are closely related to the phenotypes of living organisms and provide information on biochemical activities by reflecting the substrates and products of cellular metabolism. The transcriptome does not always correlate with the proteome, and the translated proteome might not be functionally active. Therefore, their changes do not always result in phenotypic alterations. Unlike the genome or proteome, the metabolome is often called the molecular phenotype of living organisms and is easily translated into biological conditions and disease states. Here, we review the general strategies of mass spectrometry-based metabolomics. Targeted metabolome or lipidome analysis is discussed, as well as nontargeted approaches, with a brief explanation of the advantages and disadvantages of each platform. Biomedical applications that use mass spectrometry-based metabolomics are briefly introduced.

Multiple Apocrine Hidrocystoma / 대한피부과학회지

No abstract available.

A Case of Muir-Torre Syndrome Confirmed by Genetic Mutation Analysis / 대한피부과학회지

No abstract available.

Performance of Four Anti-Heparin/Platelet Factor 4 Immunoassays for the Diagnosis of Heparin-Induced Thrombocytopenia

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a significant complication of heparin therapy induced by antibodies to heparin/platelet factor 4 (PF4) complexes. We investigated the diagnostic performance of four commercial immunoassays that detect the anti-heparin/PF4 antibody. METHODS: Four different anti-heparin/PF4 antibody assays were performed in 39 patients with suspected HIT: HemosIL AcuStar HIT-IgG, HemosIL AcuStar HIT-total antibody (Ab) (Instrumentation Laboratory, USA), STic Expert HIT (Diagnostica Stago, France), and PF4 Enhanced (Immucor GTI Diagnostics, USA). Patients were diagnosed with HIT when the Chong score was > or =5. RESULTS: The estimated sensitivity and specificity for diagnosis of HIT were 33.3% and 80.0% for AcuStar HIT-IgG, 55.6% and 53.3% for AcuStar HIT-total Ab, 100.0% and 37.9% for STic Expert HIT, and 33.3% and 66.7% for PF4 Enhanced. All specificities significantly increased when 4Ts scores were included in the diagnosis. The areas under the curves (AUCs) for predicting thrombosis in the AcuStar HIT-IgG, AcuStar HIT-total Ab, and PF4 Enhanced assays were 0.639, 0.522, and 0.681, respectively. When the results of each assay were analysed along with 4Ts scores, the AUC increased to 0.927 in the AcuStar HIT-IgG assay and 0.944 in the AcuStar HIT-total Ab and PF4 Enhanced assays. CONCLUSIONS: The STic Expert HIT assay had high sensitivity but low specificity for diagnosis of HIT. The performances of the three other immunoassays were comparable to each other. Specificity significantly increased when assay data were combined with 4Ts scores. Differences in the diagnostic performance of the four immunoassays were not evident, and simultaneous consideration of clinical scoring systems improved performance.

Activation of the Intrinsic Coagulation Pathway in Patients With Chronic Urticaria

PURPOSE: Although coagulation activation has been reported in chronic urticaria, data pertaining to detailed changes in coagulation factors and global coagulation status are lacking. The current study evaluated global coagulation status in patients with chronic urticaria using thrombin generation assay (TGA) and the levels of individual coagulation factors. METHODS: Patients with chronic urticaria (n=57) and 20 healthy controls were enrolled. TGA was performed under stimulation with 2 concentrations of tissue factor (TF). Coagulation factors and conventional coagulation assays were also analyzed. RESULTS: Although patients with chronic urticaria showed prolonged activated partial thromboplastin time, prothrombin time did not differ significantly between patients and controls. In both 1 pM and 5 pM TF-stimulated TGA, peak thrombin and endogenous thrombin potential (ETP) levels were markedly decreased in patients with chronic urticaria. As expected, intrinsic coagulation factors (VIII, IX, and XII), as well as coagulation factors of the common pathway (II, V, and X), were consistently decreased. Additionally, D-dimer was significantly increased in patients as compared to controls. In multivariate regression analysis, the presence of chronic urticaria was the only significant independent contributor to the low ETP value. CONCLUSIONS: Chronic urticaria is characterized by in vivo coagulation activation through the intrinsic coagulation pathway, which can be measured with sensitivity using TGA.

A Case of Congenital Mucinous Nevus on the Back / 대한피부과학회지

Mucinous nevus is a rare entity classified as either cutaneous mucinosis or connective tissue nevi. Clinically, grouped papules or plaques grow to form a verrucous or nevoid feature usually on the trunk. It can be present since birth or early childhood. Histologically, it consists of mucin deposits localized in the superficial dermis with or without epidermal changes. An 18-year-old boy presented with asymptomatic multiple grouped brown papules and coalescent plaques on his lower back that had been present since birth. Histological examination showed a band-like mucin deposit in the papillary dermis. To our knowledge, there have been only few reports of mucinous nevus in the literature. Here, we report a case of mucinous nevus present since birth, including a review of relevant literature.

A Case of Microvenular Hemangioma on the Scalp / 대한피부과학회지

Microvenular hemangioma is a relatively rare, acquired, and slow-growing benign vascular lesion that usually arises as a small, reddish papule or plaque in young to middle-aged individuals. It commonly occurs on the arms, trunk, or legs. Histologically, it consists of irregular branching capillaries and venules involving the full thickness of the reticular dermis. A 38-year-old woman presented for 3 years with a solitary reddish nodule on the scalp. Histological examination showed irregular venules throughout the dermis. We report this case of microvenular hemangioma developing on the scalp, an unusual location.

Collagenoma in Brother and Sister / 대한피부과학회지

No abstract available.

Mitochondrial dysfunction and activation of iNOS are responsible for the palmitate-induced decrease in adiponectin synthesis in 3T3L1 adipocytes

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are considered the key determinants of insulin resistance. Impaired mitochondrial function in obese animals was shown to induce the ER stress response, resulting in reduced adiponectin synthesis in adipocytes. The expression of inducible nitric oxide synthase (iNOS) is increased in adipose tissues in genetic and dietary models of obesity. In this study, we examined whether activation of iNOS is responsible for palmitate-induced mitochondrial dysfunction, ER stress, and decreased adiponectin synthesis in 3T3L1 adipocytes. As expected, palmitate increased the expression levels of iNOS and ER stress response markers, and decreased mitochondrial contents. Treatment with iNOS inhibitor increased adiponectin synthesis and reversed the palmitate-induced ER stress response. However, the iNOS inhibitor did not affect the palmitate-induced decrease in mitochondrial contents. Chemicals that inhibit mitochondrial function increased iNOS expression and the ER stress response, whereas measures that increase mitochondrial biogenesis (rosiglitazone and adenoviral overexpression of nuclear respiratory factor-1) reversed them. Inhibition of mitochondrial biogenesis prevented the rosiglitazone-induced decrease in iNOS expression and increase in adiponectin synthesis. These results suggest that palmitate-induced mitochondrial dysfunction is the primary event that leads to iNOS induction, ER stress, and decreased adiponectin synthesis in cultured adipocytes.

Huge Gastric Schwannoma Characterized by a Gastric Ulcer During Endoscopy / 대한소화기내시경학회지

Gastric schwannomas are very rare mesenchymal tumors that can occur throughout the gastrointestinal tract, but are most commonly found in the stomach. The majority of patients have no symptoms, while others may complain of epigastric pain or upper gastrointestinal ulcer bleeding. Endoscopic examination of a gastric schwannoma commonly reveals a protrusive mass, but, as in this case, many types of ulceration can be observed with central necrosis. We report on a 62-year-old woman with endoscopic findings of 1 cm sized necrotizing ulceration and an 11 cm sized submucosal mass on radiological examinations. The patient underwent a wedge-shaped resection of the stomach and segmental resection of the transverse colon. Both histological and immunohistochemical staining revealed a gastric schwannoma.

A case of eosinophilic gastroenteritis with eosinophilic ascites / 대한내과학회지

Eosinophilic gastroenteritis is an uncommon disease of unknown cause characterized by eosinophilic infiltration in various areas of the gastrointestinal tract with gastrointestinal symptoms. It is generally classified according to the layer of the gastrointestinal tract involved. Eosinophilic infiltration of the serosa is the rarest form of presentation and may manifest eosinophilic ascites. We report a case of a 29-year-old woman who experienced rapidly progressing abdominal distension and pain. A diffuse erythematous change of the gastric mucosa was observed on gastroscopy. An abdominal computed tomography and colonoscopy showed diffuse wall thickening of the small bowel and colon with a large amount of ascites. Eosinophilic infiltration was confirmed by multiple biopsies of the gastrointestinal tract and peritoneal fluid analysis. The patient was treated with corticosteroid and responded dramatically.

A Case of Ureteral Endometriosis associated with Hydronephrosis / 대한산부인과학회지

Endometriosis affecting the urinary tract is very rare disease. The ureteral endometriosis is mostly asymptomatic for a long time, and associated with nonspecific symptoms such as abdominal or flank pain, renal colic, voiding difficulty and gross hematuria. Radiologic and laboratory findings show nonspecific findings, and the diagnosis is difficult. We report a case of obstructive ureteral endometriosis associated with right hydronephorsis. This case is operated under the impression of direct compression of ureter by uterine myoma. Total abdominal hysterectomy and ureteroureterostomy were performed. Final diagnosis of ureteral endometriosis is documented by pathologic findings.

The Studies of bcl-2 Oncoprotein and Epstein-Barr Virus Expression in Malignant Lymphomas: Immunohistochemical and in situ hybridization analysis on 66 cases

Bcl-2 oncoprotein is being localized to mitochondria and interfering with programmed cell death (apoptosis) independent of promoting cell division in the lymphoid and nonlymphoid cells. The bcl-2 oncoprotein expression has been reported in follicular lymphomas as well as in diffuse non-Hodgkin's lymphoma, leukemia and a variable propotion of Hodgkin's lymphoma cases. Recent evidence suggests that some lymphomas protected from apoptosis is conferred through expression of Epstein-Barr virus(EBV) latent membrane protein which turn to cause upregulation of bcl-2. To define the role of the bcl-2 oncoprotein and EBV in lymphoid malignancy, we tried immunohistochemical studies with anti-bcl-2 antibody and In situ hybridization (ISH) with EBV-encoded small nuclear RNAs(EBER) in the paraffin embedded sections of 46 non-Hodgkin's lymphoma (NHL) cases and 20 Hodgkin's lymphoma (HL) cases. Bcl-2 oncoprotein expression was found in 37 of 46 cases (80%) of NHL with relatively strong cytoplasmic staining, and in 14 of 20 cases (70%) of HL with weak cytoplasmic staining in limited small numbers of RS, Hodgkin and lacunar cells. The widespread presence of bcl-2 oncogene in many different types of both NHL and HL supports that the extended cell survival through overexpression of bcl-2 gene protein may be a growth advantage of neoplastic lymphoid cells. In the ISH analysis for EBV, the presence of EBV was detected in 17 of 20 cases (85%) of HL, compared to 6 of 44 cases(13.6%) of NHL. It appears to be no direct correlation between overexpression of bcl-2 oncoprotein by neoplastic lymphoid cells and the presence of EBV in NHL but it seems to be a definite association between EBV and HL.

Incidence of Acute Placental Inflammation through Histopathological Analysis: One year experience in 1995 at Seoul National University Hospital

The diagnosis of acute inflammation of the placenta, represented as acute chorioamnionitis, is important in that it is associated with a poor clinical outcome for both the mother and the fetus, including major perinatal morbidities such as sepsis, respiratory distress syndrome, and CNS damage. However, current medical trends in Korea seem to overlook the significance of a histopathological diagnosis of acute placental inflammation, mainly due to the indifferences of clinicians and pathologists. Since late 1993, histopathological examinations have been performed on preterm placentas at Seoul National University. These examinations have demonstrated acute placental inflammation in a significant number of cases. In the present study the incidence of acute placental inflammation was analyzed in 521 placentas which were submitted for pathological examinations in 1995. Examinations were performed to provide basic information on the incidence and profile of acute placental inflammation in this hospital and, thereby, to emphasize the significance of histopathological examinations of the placenta in the routine surgical pathology service. Among the 521 placentas, acute inflammation was found in 194 cases (37.2%). In preterm placentas acute inflammation was found in 39.6% of the cases (67/169), while 36.1% (127/352) of term placentas showed acute inflammation. Taking the delivery mode into account, 26.3% (49/186) of the placentas delivered by cesarean section showed acute inflammation, while 43.3% (145/335) of the transvaginally delivered placentas showed inflammation. The present analysis demonstrates the existence of acute inflammation in a significant proportion of placentas with different clinical settings. The importance of a histopathological examination in routine hospital practice should be emphasized.

Clear Cell Sarcoma of the Kidney: A case in 39 year old man

Clear cell sarcoma of kidney(CCSK) is a rare pediatric neoplasm characterized by a predominating component of clear cells, a predilection for metastases to bone, and a poor prognosis. The incidence of CCSK peaks during the 2nd year of life and adult cases are very rare. We report a case of CCSK encountered in the right kidney of a 39-year-old man. Grossly, it was a lobulated mass showing infiltrative margin, measured 7x5.5x5cm and had a homogeneous gray-tan color with a soft, fish-flesh consistency. Microscopically, about half of the tumor revealed the classic pattern of CCSK, having tumor cell cords or nests separated by the characteristic alveolar capillary networks. The tumor cells had clear pale cytoplasm, bland looking round nuclei and inconspicuous nucleoli. The other half showed the epithelioid-trabecular pattern forming pseudorosette or cord-like structures. Immunohistochemically, there was only a focal positive reaction to vimentin. Ultrastructurally, the tumor cells showed the primitive nephrogenic mesenchymal differentiation such as electron lucent cytoplasm, a small amount of organelles, scanty heterochromatin, inconspicuous nucleoli, and a lack of flocculant basal lamina material around the cytoplasmic membrane. We consider that this is a case of CCSK occuring in the oldest patient ever reported, confirmed by both immunohistochemistry and electron microscopy.