Umbelliferone Ameliorates Hepatic Steatosis and Lipid-Induced ER Stress in High-Fat Diet-Induced Obese Mice

Purpose@#Among the characteristics of non-alcoholic fatty liver disease (NAFLD), hepatic steatosis is due to excessive fat accumulation and causes liver damage and lipotoxicity, which are associated with insulin resistance, endoplasmic reticulum (ER) stress, and apoptosis. Umbelliferone (UMB) has various powerful pharmacological properties, such as antioxidant, anti-hyperglycemic, anti-viral, and anti-inflammatory effects. However, the mechanism of action in hepatic steatosis and lipid-induced ER stress is still unclear. Thus, the efficacy of UMB in hepatic steatosis and palmitate (PA)-induced hepatocellular lipotoxicity was evaluated in the present study. @*Materials and Methods@#Male C57BL/6J mice (n=40) were divided into four groups: regular diet (RD), UMB-supplemented RD, high-fat diet (HFD), and UMB-supplemented HFD. All mice were fed orally for 12 weeks. In addition, the effects of UMB on lipotoxicity were investigated in AML12 cells treated with PA (250 μM) for 24 h; Western blot analysis was used to evaluate the changes in ER stress and apoptotic-associated proteins. @*Results@#Administration with UMB in HFD-fed mice reduced lipid accumulation and hepatic triglyceride (TG) as well as serum insulin and glucose levels. In AML12 cells, UMB treatment reduced lipid accumulation as indicated by decreases in the levels of lipogenesis markers, such as SREBP1, FAS, PPAR-γ, and ADRP. Furthermore, UMB reduced both oxidative stress and ER stress-related cellular apoptosis. @*Conclusion@#UMB supplementation ameliorated hepatic steatosis and improved insulin resistance by inhibiting lipid accumulation and regulating ER stress. These findings strongly suggest that UMB may be a potential therapeutic compound against NAFLD.

Association with Combined Occupational Hazards Exposure and Risk of Metabolic Syndrome: A Workers' Health Examination Cohort 2012–2021

Background@#This study aimed to evaluate the association between exposure to occupational hazards and the metabolic syndrome. A secondary objective was to analyze the additive and multiplicative effects of exposure to risk factors. @*Methods@#This retrospective cohort was based on 31,615 health examinees at the Pusan National University Yangsan Hospital in Republic of Korea from 2012–2021. Demographic and behavior-related risk factors were treated as confounding factors, whereas three physical factors, 19 organic solvents and aerosols, and 13 metals and dust were considered occupational risk factors. Time-dependent Cox regression analysis was used to calculate hazard ratios. @*Results@#The risk of metabolic syndrome was significantly higher in night shift workers (hazard ratio = 1.45: 95% confidence interval = 1.36–1.54) and workers who were exposed to noise (1.15:1.07–1.24). Exposure to some other risk factors was also significantly associated with a higher risk of metabolic syndrome. They were dimethylformamide, acetonitrile, trichloroethylene, xylene, styrene, toluene, dichloromethane, copper, antimony, lead, copper, iron, welding fume, and manganese. Among the 28 significant pairs, 19 exhibited both positive additive and multiplicative effects. @*Conclusions@#Exposure to single or combined occupational risk factors may increase the risk of developing metabolic syndrome. Working conditions should be monitored and improved to reduce exposure to occupational hazards and prevent the development of the metabolic syndrome.

Beneficial Effects of a Curcumin Derivative and Transforming Growth Factor-β Receptor I Inhibitor Combination on Nonalcoholic Steatohepatitis

Background@#Curcumin 2005-8 (Cur5-8), a derivative of curcumin, improves fatty liver disease via AMP-activated protein kinase activation and autophagy regulation. EW-7197 (vactosertib) is a small molecule inhibitor of transforming growth factor β (TGF-β) receptor I and may scavenge reactive oxygen species and ameliorate fibrosis through the SMAD2/3 canonical pathway. This study aimed to determine whether co-administering these two drugs having different mechanisms is beneficial. @*Methods@#Hepatocellular fibrosis was induced in mouse hepatocytes (alpha mouse liver 12 [AML12]) and human hepatic stellate cells (LX-2) using TGF-β (2 ng/mL). The cells were then treated with Cur5-8 (1 μM), EW-7197 (0.5 μM), or both. In animal experiments were also conducted during which, methionine-choline deficient diet, Cur5-8 (100 mg/kg), and EW-7197 (20 mg/kg) were administered orally to 8-week-old C57BL/6J mice for 6 weeks. @*Results@#TGF-β-induced cell morphological changes were improved by EW-7197, and lipid accumulation was restored on the administration of EW-7197 in combination with Cur5-8. In a nonalcoholic steatohepatitis (NASH)-induced mouse model, 6 weeks of EW-7197 and Cur5-8 co-administration alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) activity score. @*Conclusion@#Co-administering Cur5-8 and EW-7197 to NASH-induced mice and fibrotic hepatocytes reduced liver fibrosis and steatohepatitis while maintaining the advantages of both drugs. This is the first study to show the effect of the drug combination against NASH and NAFLD. Similar effects in other animal models will confirm its potential as a new therapeutic agent.

EW-7197 Attenuates the Progression of Diabetic Nephropathy in db/db Mice through Suppression of Fibrogenesis and Inflammation

Background@#Diabetic nephropathy (DN) is characterized by albuminuria and accumulation of extracellular matrix (ECM) in kidney. Transforming growth factor-β (TGF-β) plays a central role in promoting ECM accumulation. We aimed to examine the effects of EW-7197, an inhibitor of TGF-β type 1 receptor kinase (ALK5), in retarding the progression of DN, both in vivo, using a diabetic mouse model (db/db mice), and in vitro, in podocytes and mesangial cells. @*Methods@#In vivo study: 8-week-old db/db mice were orally administered EW-7197 at a dose of 5 or 20 mg/kg/day for 10 weeks. Metabolic parameters and renal function were monitored. Glomerular histomorphology and renal protein expression were evaluated by histochemical staining and Western blot analyses, respectively. In vitro study: DN was induced by high glucose (30 mM) in podocytes and TGF-β (2 ng/mL) in mesangial cells. Cells were treated with EW-7197 (500 nM) for 24 hours and the mechanism associated with the attenuation of DN was investigated. @*Results@#Enhanced albuminuria and glomerular morphohistological changes were observed in db/db compared to that of the nondiabetic (db/m) mice. These alterations were associated with the activation of the TGF-β signaling pathway. Treatment with EW-7197 significantly inhibited TGF-β signaling, inflammation, apoptosis, reactive oxygen species, and endoplasmic reticulum stress in diabetic mice and renal cells. @*Conclusion@#EW-7197 exhibits renoprotective effect in DN. EW-7197 alleviates renal fibrosis and inflammation in diabetes by inhibiting downstream TGF-β signaling, thereby retarding the progression of DN. Our study supports EW-7197 as a therapeutically beneficial compound to treat DN.

Tetrahydrocurcumin Ameliorates Kidney Injury and High Systolic Blood Pressure in High-Fat Diet-Induced Type 2 Diabetic Mice

Background@#Activation of the intrarenal renin-angiotensin system (RAS) is implicated in the pathogenesis of kidney injury and hypertension. We aimed to investigate the protective effect of tetrahydrocurcumin (THU) on intrarenal RAS expression, kidney injury, and systolic blood pressure (SBP) in high-fat diet (HFD)-induced type 2 diabetic mice. @*Methods@#Eight-week-old male mice were fed a regular diet (RD) or HFD for 12 weeks, and THU (50 or 100 mg/kg/day) was intragastrically administered with HFD. Physiological and metabolic changes were monitored and the expression of RAS components and markers of kidney injury were assessed. @*Results@#HFD-fed mice exhibited hyperglycemia, insulin resistance, and dyslipidemia compared to those in the RD group (P<0.05). Kidney injury in these mice was indicated by an increase in the ratio of albumin to creatinine, glomerular hypertrophy, and the effacement of podocyte foot processes. Expression of intrarenal angiotensin-converting enzyme, angiotensin II type I receptor, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-4, and monocyte chemoattractant protein-1 was also markedly increased in HFD-fed mice. HFD-fed mice exhibited elevated SBP that was accompanied by an increase in the wall thickness and vascular cross-sectional area (P<0.05), 12 weeks post-HFD consumption. Treatment with THU (100 mg/kg/day) suppressed intrarenal RAS activation, improved insulin sensitivity, and reduced SBP, thus, attenuating kidney injury in these mice. @*Conclusion@#THU alleviated kidney injury in mice with HFD-induced type 2 diabetes, possibly by blunting the activation of the intrarenal RASicotinamide adenine dinucleotide phosphate oxidase IV (NOX4)/monocyte chemoattractant protein 1 (MCP-1) axis and by lowering the high SBP.

Tetrahydrocurcumin Ameliorates Kidney Injury and High Systolic Blood Pressure in High-Fat Diet-Induced Type 2 Diabetic Mice

Background@#Activation of the intrarenal renin-angiotensin system (RAS) is implicated in the pathogenesis of kidney injury and hypertension. We aimed to investigate the protective effect of tetrahydrocurcumin (THU) on intrarenal RAS expression, kidney injury, and systolic blood pressure (SBP) in high-fat diet (HFD)-induced type 2 diabetic mice. @*Methods@#Eight-week-old male mice were fed a regular diet (RD) or HFD for 12 weeks, and THU (50 or 100 mg/kg/day) was intragastrically administered with HFD. Physiological and metabolic changes were monitored and the expression of RAS components and markers of kidney injury were assessed. @*Results@#HFD-fed mice exhibited hyperglycemia, insulin resistance, and dyslipidemia compared to those in the RD group (P<0.05). Kidney injury in these mice was indicated by an increase in the ratio of albumin to creatinine, glomerular hypertrophy, and the effacement of podocyte foot processes. Expression of intrarenal angiotensin-converting enzyme, angiotensin II type I receptor, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-4, and monocyte chemoattractant protein-1 was also markedly increased in HFD-fed mice. HFD-fed mice exhibited elevated SBP that was accompanied by an increase in the wall thickness and vascular cross-sectional area (P<0.05), 12 weeks post-HFD consumption. Treatment with THU (100 mg/kg/day) suppressed intrarenal RAS activation, improved insulin sensitivity, and reduced SBP, thus, attenuating kidney injury in these mice. @*Conclusion@#THU alleviated kidney injury in mice with HFD-induced type 2 diabetes, possibly by blunting the activation of the intrarenal RASicotinamide adenine dinucleotide phosphate oxidase IV (NOX4)/monocyte chemoattractant protein 1 (MCP-1) axis and by lowering the high SBP.

Delayed Diagnosis Due to Septal Perforation in Patient with Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type / 대한이비인후과학회지

Extranodal natural killer (NK)/T-cell lymphoma, nasal type is a rare non-Hodgkin lymphoma originating in the nasal cavity or in the paranasal sinuses, and is etiologically closely related with the Epstein Barr Virus infection. It is more commonly found in East Asia, South America, and Mexico than in Europe or North America. Extranodal NK/T-cell lymphoma, nasal type typically shows a crust on the nasal mucosal surface, necrosis, and inflammation. Pathologically, it presents as significant vascular damage and destruction, with apparent tissue necrosis and cytotoxicity. These neoplasms are very aggressive and can show septal perforation, diffuse ulcer lesion on the nasal mucosa, fistula or epistaxis. We experienced a case of the extranodal NK/T-cell lymphoma, nasal type at the nasal septum, which was delayed in diagnosis due to septal perforation, which occurred after septoplasty in a 47-year-old female. Thus, we report this case with a review of literatures.

A Case of Retropharyngeal Abscess Resulting from Infected Paratracheal Cyst / 대한이비인후과학회지

A paratracheal cyst is an air-filled cyst lined by a ciliated epithelium, commonly referred to as a tracheal diverticulum. The most common location of paratracheal cysts is the right side of posterolateral tracheal wall. It occurs in 0.3% to 8.1% of the total population. Most paratracheal cysts are asymptomatic and discovered incidentally on routine radiologic examination. Rarely, however, symptoms such as cough or fever are encountered and chronic infection of the paratracheal cyst usually present itself like a tucoberculosis or a tumor. There are few case reports of deep neck infection caused by a paratracheal cyst. We report a case of retropharyngeal abscess resulting from an infected paratracheal cyst.

Effects of Oxytocin on Cell Proliferation in a Corticotroph Adenoma Cell Line

BACKGROUND: Oxytocin (OXT) has been reported to act as a growth regulator in various tumor cells. However, there is a paucity of data on the influence of OXT on cell proliferation of corticotroph adenomas. This study aimed to examine whether OXT affects cell growth in pituitary tumor cell lines (AtT20 and GH3 cells) with a focus on corticotroph adenoma cells. METHODS: Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were conducted with AtT20 cells to confirm the effects of OXT on hormonal activity; flow cytometry was used to assess changes in the cell cycle after OXT treatment. Moreover, the impact of OXT on proliferating cell nuclear antigen (PCNA), nuclear factor κB, and mitogen-activated protein kinase signaling pathway was analyzed by Western blot. RESULTS: OXT treatment of 50 nM changed the gene expression of OXT receptor and pro-opiomelanocortin within a short time. In addition, OXT significantly reduced adrenocorticotropic hormone secretion within 1 hour. S and G2/M populations of AtT20 cells treated with OXT for 24 hours were significantly decreased compared to the control. Furthermore, OXT treatment decreased the protein levels of PCNA and phosphorylated extracellular-signal-regulated kinase (P-ERK) in AtT20 cells. CONCLUSION: Although the cytotoxic effect of OXT in AtT20 cells was not definite, OXT may blunt cell proliferation of corticotroph adenomas by altering the cell cycle or reducing PCNA and P-ERK levels. Further research is required to investigate the role of OXT as a potential therapeutic target in corticotroph adenomas.

Mannosylerythritol lipids ameliorate ultraviolet A-induced aquaporin-3 downregulation by suppressing c-Jun N-terminal kinase phosphorylation in cultured human keratinocytes

Mannosylerythritol lipids (MELs) are glycolipids and have several pharmacological efficacies. MELs also show skin-moisturizing efficacy through a yet-unknown underlying mechanism. Aquaporin-3 (AQP3) is a membrane protein that contributes to the water homeostasis of the epidermis, and decreased AQP3 expression following ultraviolet (UV)-irradiation of the skin is associated with reduced skin moisture. No previous study has examined whether the skin-moisturizing effect of MELs might act through the modulation of AQP3 expression. Here, we report for the first time that MELs ameliorate the UVA-induced downregulation of AQP3 in cultured human epidermal keratinocytes (HaCaT keratinocytes). Our results revealed that UVA irradiation decreases AQP3 expression at the protein and messenger RNA (mRNA) levels, but that MEL treatment significantly ameliorated these effects. Our mitogen-activated protein kinase inhibitor analysis revealed that phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38, mediates UVA-induced AQP3 downregulation, and that MEL treatment significantly suppressed the UVA-induced phosphorylation of JNK. To explore a possible mechanism, we tested whether MELs could regulate the expression of peroxidase proliferator-activated receptor gamma (PPAR-γ), which acts as a potent transcription factor for AQP3 expression. Interestingly, UVA irradiation significantly inhibited the mRNA expression of PPAR-γ in HaCaT keratinocytes, whereas a JNK inhibitor and MELs significantly rescued this effect. Taken together, these findings suggest that MELs ameliorate UVA-induced AQP3 downregulation in HaCaT keratinocytes by suppressing JNK activation to block the decrease of PPAR-γ. Collectively, our findings suggest that MELs can be used as a potential ingredient that modulates AQP3 expression to improve skin moisturization following UVA irradiation-induced damage.

Protective Effects of Curcumin on Renal Oxidative Stress and Lipid Metabolism in a Rat Model of Type 2 Diabetic Nephropathy

PURPOSE: Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy. MATERIALS AND METHODS: Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys. RESULTS: Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling. CONCLUSION: Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway.

Polarized and Stage-Dependent Distribution of Immunoreactivity for Novel PDZ-Binding Protein Preso1 in Adult Neurogenic Regions

BACKGROUND: Adult neural stem cells have the potential for self-renewal and differentiation into multiple cell lineages via symmetric or asymmetric cell division. Preso1 is a recently identified protein involved in the formation of dendritic spines and the promotion of axonal growth in developing neurons. Preso1 can also bind to cell polarity proteins, suggesting a potential role for Preso1 in asymmetric cell division. METHODS: To investigate the distribution of Preso1, we performed immunohistochemistry with adult mouse brain slice. Also, polarized distribution of Preso1 was assessed by immunocytochemistry in cultured neural stem cells. RESULTS: Immunoreactivity for Preso1 (Preso1-IR) was strong in the rostral migratory stream and subventricular zone, where proliferating transit-amplifying cells and neuroblasts are prevalent. In cultured neural stem cells, Preso1-IR was unequally distributed in the cell cytosol. We also observed the distribution of Preso1 in the subgranular zone of the hippocampal dentate gyrus, another neurogenic region in the adult brain. Interestingly, Preso1-IR was transiently observed in the nuclei of doublecortin-expressing neuroblasts immediately after asymmetric cell division. CONCLUSION: Our study demonstrated that Preso1 is asymmetrically distributed in the cytosol and nuclei of neural stem/progenitor cells in the adult brain, and may play a significant role in cell differentiation via association with cell polarity machinery.

Effects of ferulic acid on diabetic nephropathy in a rat model of type 2 diabetes

Diabetic nephropathy is the most serious complication in diabetes mellitus. It is known that oxidative stress and inflammation play a central role in the development of diabetic nephropathy. In this study, we investigated that ferulic acid (FA) known as anti-oxidative agent could effect on diabetic nephropathy by anti-oxidative and anti-inflammatory mechanism. We examined the effects of FA in obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats. We treated FA to experimental rats from 26 to 45 weeks of age. We evaluated ACR, MDA and MCP-1 in 24 h urine and examined renal histopathology and morphologic change in extracted kidneys from rats. Also, we evaluated the ROS production and MCP-1 levels in cultured podocyte after FA treatment. In the FA-treated OLETF rats, blood glucose was significantly decreased and serum adiponectin levels were increased. Urinary ACR was significantly reduced in FA-treated OLETF rats compared with diabetic OLETF rats. In renal histopathology, FA-treated OLETF rats showed decreased glomerular basement membrane thickness, glomerular volume, and mesangial matrix expansion. FA treatment decreased oxidative stress markers and MCP-1 levels in 24 h urine of rats and supernatants of cultured podocyte. In conclusion, it was suggested that FA have protective and therapeutic effects on diabetic nephropathy by reducing oxidative stress and inflammation.

Treatment of Type 2 Distal Clavicle Fracture using Wolter Plate

PURPOSE: This study examined the clinical results of the treatment of type 2 distal clavicle fracture with using a Wolter plate. MATERIALS AND METHODS: Between 2004 and 2007, 16 patient treated for type 2 distal clavicle fracture using a Wolter plate were included in this study. Their average age was 32.6 years and the postoperative mean follow-up period was 22.9 months. The reduction and union were qualified according to the immediate post-operative and final radiographs. The functional outcome was evaluated by Kona's system and the Constant score RESULTS: By Kona's functional evaluation, there were 12 cases with excellent results, 3 cases with good results and 1 case of fair results and the average Constant score was 90. All 16 cases showed bony union. As complications, there was 1 case in which the protruded hook of the plate could be palpated at the skin, and 1 case showed an acromial fracture, but all the cases dispalyed successful bony union and there was no acromioclavicular joint arthritis, infection or any other complications. CONCLUSION: Wolter plate fixation for type 2 distal clavicle fracture is a reliable surgical method for satisfactory reduction and rigid fixation, a lower incidence of nonunion and excellent clinical result

Treatment of Chronic Ankle Lateral Instability using Modified Brostrom Procedure with Anchor suture&Arthroscopy / 대한족부족관절학회지

PURPOSE: To evaluate the result of modified Brostrom procedure with anchor suture and explore associate lesion under arthroscopy for chronic lateral instability. MATERIALS AND METHODS: From May 2005 to March 2009, Retrospective analysis of 126 patients with chronic lateral instability who underwent modified Brostrom procedure with anchor suture and arthroscopic procedure was done. Mean follow-up period was 13 months. RESULTS: Chronic lateral instability of the ankle almost had local synovitis by arthroscopic examination. There were osteochondral lesion of talus on the anteromedial aspect in 63 cases, on the anterolateral aspect in 25 cases, osteochondral lesion of tibia side in 8 cases, fat hypertrophy of tibiofibular space in 120 cases, anterior fat impingement in 26 cases, intra-articular loose body in 13 cases. Mean Karlsson scoring scale was improve from 53 preoperatively to 91 postoperatively, There were 70 cases excellent, 27 cases good, 26 cases fair, 3 cases poor result according to the Sefton procedure. CONCLUSION: Modified Brostrom procedure with anchor suture and arthroscopic procedure are reliable treatment method for chronic ankle lateral instability which has intraarticular pathology.

Differential Methylation Pattern of ID4, SFRP1, and SHP1 between Acute Myeloid Leukemia and Chronic Myeloid Leukemia

To gain insight into the differential mechanism of gene promoter hypermethylation in acute and chronic leukemia, we identified the methylation status on one part of 5'CpG rich region of 8 genes, DAB2IP, DLC-1, H-cadherin, ID4, Integrin alpha4, RUNX3, SFRP1, and SHP1 in bone marrows from acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) patients. Also, we compared the methylation status of genes in AML and CML using methylation-specific PCR (MSP). The frequencies of DNA methylation of ID4, SFRP1, and SHP1 were higher in AML patients compared to those in CML patients. In contrast, no statistical difference between AML and CML was detected for other genes such as DLC-1, DAB2IP, H-cadherin, Integrin alpha4, and RUNX3. Taken together, these results suggest that these methylation-controlled genes may have different roles in AML and CML, and thus, may act as a biological marker of AML.

Differential Methylation Pattern of ID4, SFRP1, and SHP1 between Acute Myeloid Leukemia and Chronic Myeloid Leukemia

To gain insight into the differential mechanism of gene promoter hypermethylation in acute and chronic leukemia, we identified the methylation status on one part of 5'CpG rich region of 8 genes, DAB2IP, DLC-1, H-cadherin, ID4, Integrin alpha4, RUNX3, SFRP1, and SHP1 in bone marrows from acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) patients. Also, we compared the methylation status of genes in AML and CML using methylation-specific PCR (MSP). The frequencies of DNA methylation of ID4, SFRP1, and SHP1 were higher in AML patients compared to those in CML patients. In contrast, no statistical difference between AML and CML was detected for other genes such as DLC-1, DAB2IP, H-cadherin, Integrin alpha4, and RUNX3. Taken together, these results suggest that these methylation-controlled genes may have different roles in AML and CML, and thus, may act as a biological marker of AML.

Effects of Deafferented Sensory Inputs on c-fos mRNA Expression in Medial Vestibular Nucleus of Rats Following Unilateral Labyrinthectomy / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Fos is a protein product of proto-oncogene c-fos, which is induced by various kinds of stimulations such as noxious, physiologic and electrical stimulations. In the vestibular system, there have been several evidences that c-fos was expressed in the brainstem vestibular nuclei during vestibular compensation following unilateral labyrinthectomy (ULX). In this study, the author evaluated the effect of deafferented sensory inputs on the c-fos mRNA expression in the medial vestibular nucleus of unilaterally labyrinthectomized rats. MATERIALS AND METHODS: Animals in the experimental group underwent tarsorraphy and cervical dorsal ganglionectomy to deprive them of visual and proprioceptive sensory inputs immediately after ULX, whereas the experimental group II did not receive any procedure after ULX. Expression of c-fos mRNA was demonstrated by in situ hybridization technique. All animals were sacrificed at 1, 3, 6, 9, 24, 48 hours after ULX and frozen sectioned tissues of brainstem were used in situ hybridization. RESULTS: Three hours after ULX, the expression of c- fos mRNA was increased in the dorsal portion of medial vestibular nucleus (dMVN) in both groups and after 6 hours of ULX, it was markedly reduced. In group I (deafferented), however, asymmetric expression was observed in 24 hours after the operation. In group II, the increased expression of c-fos mRNA in the ipsilateral dMVN continued until 9 hours after the operation and thereafter, the asymmetry of c-fos mRNA expressions between the ipsilateral and contralateral dMVN was decreased. CONCLUSION: These findings suggest that vision and proprioception influenced the expression of c-fos mRNA in the brainstem medial vestibular nucleus after ULX and corrected the asymmetric expression between the healthy and lesioned nuclei earlier than the deafferented group.

Role of Superoxide Dismutase in Eustachian Tube of Rat with Acute Otitis Media / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Superoxide dismutase (SOD) is an important protective enzyme against biochemical injury associated with inflammatory reaction. SOD are found in the epithelium of the normal middle ears and lesser amounts are found in infected ears. However, the localization of the SOD in the Eustachian tube in the normal and infected ear has been poorly studied. This study attempted to determine the distribution of SOD and how it changes from normal to infected. MATERIALS AND METHODS:We used fifty male Sprague-Dawley rats to observe the SOD expression and the change of its amount in the Eustachian tube using immunohistochemical method and western blotting. RESULTS: In normal rats, SOD was found in the epithelium of Eustachian tube and lower amounts were found in the connective tissue layers. In the streptococcus-infected ears, SOD was found in the similar pattern, but the infected tubal mucosa showed extensive submucosal edema and stained poorly with SOD, compared to the normal Eustachian tube mucosa. The amounts of SOD was 1.48+/-0.44ng/mg of protein in the normal mucosa and decreased markedly to 0.62+/-0.37ng/mg in the infected cosa. CONCLUSION: SOD was identified in the normal Eustachian tube; the amount decreased during the infected period. This finding suggests that SOD may have a protective role in the pathogenic state.

Expression of Ki-67 and Topoisomerase IIa in Human Middle Ear Cholesteatoma Epithelium / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Cholesteatoma is a destructive lesion of the middle ear or mastoid process. The development of human cholesteatoma is due to the altered control of cellular proliferation in part, which tilts the balance toward the aggressive, invasive growth of squamous epithelium within the middle ear. Many efforts were performed to prove overproliferative characteristics of cholesteatoma using various proliferation markers. Nonetheless, trigger site of overproliferation within the overgrowing epithelium of cholesteatoma is still ill defined. MATERIALS AND METHODS: In this study, we used the monoclonal antibody Ki-67 and Topoisomerase II, a marker of active proliferation, on frozen sections obtained from 12 cholesteatoma samples and observed expression of these markers in three different regions, from normal meatal skin, transitional zone and cholesteatoma sac. RESULTS: The results were interpreted on the basis of nuclear staining and percentage of positively stained cells (labeling index). We found that labeling indices of cholesteatoma and transitional zone were significantly increased compared with that of normal meatal skin. CONCLUSION: This result suggested that initiating of overproliliferation of cholesteatoma epithelium started from the transitional zone.