Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases

Nonalcoholic fatty liver disease (NAFLD) is a major public health problem and the most common form of chronic liver disease, affecting 25% of the global population. Although NAFLD is closely linked with obesity, insulin resistance, and type 2 diabetes mellitus, knowledge on its pathogenesis remains incomplete. Emerging data have underscored the importance of Rho-kinase (Rho-associated coiled-coil-containing kinase [ROCK]) action in the maintenance of normal hepatic lipid homeostasis. In particular, pharmacological blockade of ROCK in hepatocytes or hepatic stellate cells prevents the progression of liver diseases such as NAFLD and fibrosis. Moreover, mice lacking hepatic ROCK1 are protected against obesity-induced fatty liver diseases by suppressing hepatic de novo lipogenesis. Here we review the roles of ROCK as an indispensable regulator of obesity-induced fatty liver disease and highlight the key cellular pathway governing hepatic lipid accumulation, with focus on de novo lipogenesis and its impact on therapeutic potential. Consequently, a comprehensive understanding of the metabolic milieu linking to liver dysfunction triggered by ROCK activation may help identify new targets for treating fatty liver diseases such as NAFLD.

Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases

Nonalcoholic fatty liver disease (NAFLD) is a major public health problem and the most common form of chronic liver disease, affecting 25% of the global population. Although NAFLD is closely linked with obesity, insulin resistance, and type 2 diabetes mellitus, knowledge on its pathogenesis remains incomplete. Emerging data have underscored the importance of Rho-kinase (Rho-associated coiled-coil-containing kinase [ROCK]) action in the maintenance of normal hepatic lipid homeostasis. In particular, pharmacological blockade of ROCK in hepatocytes or hepatic stellate cells prevents the progression of liver diseases such as NAFLD and fibrosis. Moreover, mice lacking hepatic ROCK1 are protected against obesity-induced fatty liver diseases by suppressing hepatic de novo lipogenesis. Here we review the roles of ROCK as an indispensable regulator of obesity-induced fatty liver disease and highlight the key cellular pathway governing hepatic lipid accumulation, with focus on de novo lipogenesis and its impact on therapeutic potential. Consequently, a comprehensive understanding of the metabolic milieu linking to liver dysfunction triggered by ROCK activation may help identify new targets for treating fatty liver diseases such as NAFLD.

Combined Aerobic and Resistance Exercise Training Reduces Circulating Apolipoprotein J Levels and Improves Insulin Resistance in Postmenopausal Diabetic Women

BACKGROUND: Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in patients with type 2 diabetes mellitus.METHODS: Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeostatic model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed.RESULTS: In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P<0.05 and P<0.001, respectively). In the EXE group, 12 weeks of exercise resulted in significant decreases in body weight, percent body fat, and HOMA-IR indices. Concurrently, weight-adjusted appendicular skeletal muscle mass (ASM/wt) was increased in the EXE group compared with the CON group. Importantly, changes in the ApoJ level were significantly correlated with changes in ASM/wt.CONCLUSION: Exercise training resulted in a significant decrease in the circulating ApoJ level, with changes in ApoJ associated with an improvement in some insulin resistance indices. These data suggest that circulating ApoJ may be a useful metabolic marker for assessing the effects of exercise on insulin resistance.

Metformin Ameliorates Lipotoxic β-Cell Dysfunction through a Concentration-Dependent Dual Mechanism of Action

BACKGROUND: Chronic exposure to elevated levels of free fatty acids contributes to pancreatic β-cell dysfunction. Although it is well known that metformin induces cellular energy depletion and a concomitant activation of AMP-activated protein kinase (AMPK) through inhibition of the respiratory chain, previous studies have shown inconsistent results with regard to the action of metformin on pancreatic β-cells. We therefore examined the effects of metformin on pancreatic β-cells under lipotoxic stress.METHODS: NIT-1 cells and mouse islets were exposed to palmitate and treated with 0.05 and 0.5 mM metformin. Cell viability, glucose-stimulated insulin secretion, cellular adenosine triphosphate, reactive oxygen species (ROS) levels and Rho kinase (ROCK) activities were measured. The phosphorylation of AMPK was evaluated by Western blot analysis and mRNA levels of endoplasmic reticulum (ER) stress markers and NADPH oxidase (NOX) were measured by real-time quantitative polymerase chain reaction analysis.RESULTS: We found that metformin has protective effects on palmitate-induced β-cell dysfunction. Metformin at a concentration of 0.05 mM inhibits NOX and suppresses the palmitate-induced elevation of ER stress markers and ROS levels in a AMPK-independent manner, whereas 0.5 mM metformin inhibits ROCK activity and activates AMPK.CONCLUSION: This study suggests that the action of metformin on β-cell lipotoxicity was implemented by different molecular pathways depending on its concentration. Metformin at a usual therapeutic dose is supposed to alleviate lipotoxic β-cell dysfunction through inhibition of oxidative stress and ER stress.

Effects of the Elderly's Health Statuses, Health Behavior, and Social Relations on Their Health-related Quality of Life: Focusing on Family Types

PURPOSE: The purpose of this study is to identify the effects of the elderly's health statuses, health behavior, and social relations on their health-related quality of life (HRQoL) according to their family types. METHODS: The subjects of this study were 1000 elderly persons (298 living alone, 420 living with their spouses, and 282 living with their family)living in C city in Gangwon Province. Data were collected through structured questionnaires from July 20 to September 30, 2015. The SPSS/WIN program was used for data analysis. RESULTS: The HRQoL of the elderly living alone was much lower than the other groups. The most influential factors on the HRQoL include self-rated health and depressive symptoms in all three groups. Social activities and skipping meals were associated with the HRQoL of the elderly living alone and living with their spouses, while marital status, number of chronic disease, and instrumental activities of daily living were associated with the HRQoL of the elderly living with their family. CONCLUSION: Nurses should take into account family types when designing interventions for improving the HRQoL of the elderly.

A Case of Pancreatitis Associated with Hyperfunctioning Intrathyroidal Parathyroid Adenoma / 대한이비인후과학회지

Both intrathyroidal parathyroid adenoma and acute pancreatitis from hyperparathyroidism are rare disorders. We report a case of acute pancreatitis from hyperfunctioning intrathyroidal parathyroid adenoma in a 40-year-old man with severe abdominal pain. Serum chemistry values show-ed high amylase, lipase, calcium and intact parathyroid hormone level, and abdominal CT revealed acute pancreatitis. A 7 mm lesion was detected inside the left upper pole of thyroid on neck ultrasonography and confirmed to be a parathyroid lesion based on fine needle aspiration cytology. After exploratory parathyroidectomy, symptoms subsided. In patients who present with acute pancreatitis, hyperparathyroidism should also be considered if risk factors such as alcohol ingestion, gallstone, previous endoscopic retrograde cholangiopancreatography, and abdominal trauma do not exist. Exploratory parathyroidectomy should be performed in a case of acute pancreatitis from primary hyperparathyroidism.

A Case of Parathyroid Carcinoma Presenting as Brown Tumors / 대한이비인후과학회지

Carcinoma of the parathyroid gland has been reported as a rare disease occurring in 0.5 to 4% of patients with the primary hyperparathyroidism. Brown tumor is characterized as the terminal stage of remodeling processes during the primary or secondary hyperparathyroidism. Brown tumor induced by the primary hyperparathyroidism can commonly occur in the ribs, clavicle, and pelvic bone. We experienced a case of a 29-year old female patient, who had parathyroid carcinoma leading to primary hyperparathyroidism, followed by multiple Brown tumor. We present this case of parathyroid carcinoma with Brown tumors with a brief review of literature.

Clinical Characteristics of Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Diffuse sclerosing variant (DSV) is a rare variant of papillary thyroid carcinoma (PTC) and has been adopted as a histologic variant. Due to the limited number of cases and the heterogeneity of the tumor's clinical behavior, there is no consensus for DSV's optimal treatment and post-operative follow-up. The purpose of this study is to evaluate the clinical manifestation, recurrence and prognosis of 10 patients with DSV. SUBJECTS AND METHOD: We retrospectively reviewed ten consecutive patients in whom DSV was first observed between 2000 and 2012. All patients are presently under active follow-up at Korea Cancer Center Hospital. Patients underwent a total thyroidectomy with central compartment and laterocervical lymph node dissection only when this involvement was documented by pre-surgery ultrasound examination with fine needle aspiration biopsy. RESULTS: The mean observation interval was 41.6 months. The ratio of male to female was 1 : 9, and the age of incidence was 34.2+/-11.4. The average size of mass was measured 2.9+/-1.9 cm. Upon the diagnosis, eight cases had central and lateral neck lymph nodal metastasis, which was confirmed during the operation. There was no distant metastasis, but one case was confirmed with lung metastasis during the follow-up period. There was no mortality during the follow-up periods in all ten cases. CONCLUSION: DSV of PTC has high risk characteristics of large tumor size, extrathyroidal extension, and multiple lymph nodes metastasis. We may expect comparable outcome with classical PTC by proper surgical treatment and postoperative radioactiveiodine ablation.

CYP2C9 Mutation Affecting the Individual Variability of Warfarin Dose Requirement

Warfarin is a frequently prescribed anticoagulant in rehabilitation patients. Adverse drug reactions of warfarin were reported as bleeding and cutaneous microvascular thrombosis. Major bleeding, such as intracranial hemorrhage and psoas hematoma, in patients receiving anticoagulation therapy is a rare condition, but sometimes very serious complication that can even be fatal. Patient-specific factors (eg, age, body size, race, concurrent diseases, and medications) explain some of the individual variability in warfarin dose, but genetic factors, which influence warfarin response, explain a significantly higher proportion of the variability in the dose. There are two identified genes that are responsible for the main proportion of the genetic effect: CYP2C9, which codes for the enzyme cytochrome P450 2C9 that metabolizes S-warfarin, and VKORC1, which codes for warfarin's target, vitamin K epoxide reductase. We report a case of intolerance to warfarin dosing, due to impaired drug metabolism in a patient with CYP2C9*1/*3 and VKORC 1173TT. Fortunately, there are no severe complications.

A Case of Delayed Onset Nephrogenic Systemic Fibrosis After Gadolinium Based Contrast Injection

Nephrogenic systemic fibrosis (NSF) is a rare fibrosing disorder of the skin and joints that occurs in patients with advanced renal insufficiency. This condition is progressive and can be seriously disabling. Gadolinium based contrast agent (GBCA) has been identified as a potential cause of this condition. A 56-years-old man in hemodialysis developed stiffness and contracture of the whole limbs eight years after frequent GBCA exposure for cervical magnetic resonance imaging. For the first time in Korea, we report late-onset nephrogenic systemic fibrosis after GBCA exposure and performed an electrophysiologic study of this condition.

Immediate Clinical and Biomechanical Effects of Low-dye Taping in Patients with Plantar Heel Pain / 대한스포츠의학회지

Plantar heel pain is common musculoskeletal disorder of the foot related to sports activity. Treatment of the plantar heel pain is usually conservative including low-dye (LD) taping. We evaluated the immediate clinical and biomechanical effect of LD taping. 19 patients who had plantar heel pain with fat pad tenderness or tenderness on plantar fascia insertion area participated in this study. We assessed plantar pressure change with foot pressure analysis system, fat pad depth changes with ultrasonography, pain improvement with visual analogue scale before and after LD taping. Patient treated with LD taping showed the decrease in maximum peak pressure and pressure time integral, and there was not a significant difference between pre and post maximal velocity, average velocity, distance of center of pressure. Fat pad depth increase (mean 1.67 mm, p<0.05) and pain improvement (mean 1.91 on visual analog scale, p<0.05). LD taping restrict midtarsal joint, correct hindfoot pronation, and provide fat pad depth increase and pain improvement, immediately.

Perception of Balance Training and Evaluation / 대한스포츠의학회지

The purpose of this study was to survey the athletic trainers' recognition, need and evaluation for balance training and to investigate training and evaluation methods in the actual implementation. One hundred fifty trainers were participated in the survey. The study questionnaire of 24 encompassed five separated issues; basic characteristics of trainers, awareness and the need for balance, balance assessment and training content, assessment and training equipment, and education and need. Balance training were recognized as simple balance training in 20.7% of trainers, and as proprioception in 64.9%. Trainers with high needs of balance training were 69.4%. The percentage of trainers with protocol of balance training were 73.9%, and the trainers with complex equipments including software and hardware were 66.7%. Trainers with needs of education for training protocol, theoretical education for balance, and training equipment were 79.3%, 56.8%, and 63.1%. The results showed that educations for concept of balance training and sports injury rehabilitation, and research opportunities had to be provided to athlete trainers. We think that the results of this study can help athlete trainers to apply high-quality sports rehabilitation for athletes.

Low Energy Extracorporeal Shock Wave Therapy for Stress Fracture of the Anterior Cortex of the Tibia / 대한스포츠의학회지

Anterior cortex of the tibia is one of the intractable stress fracture sites ocurring in athletes, which are result of repetitive use damage that exceeds the intrinsic ability of the bone to repair itself. It is sometimes difficulty to repair the anterior cortical stress fracture, which result in delayed union or nonunion. Extracorporeal shock wave therapy (ESWT) can be an useful method in the management of stress fracture of the anterior cortex of the tibia. We present a case of an young athlete affected by chronic stress fractures of the anterior cortex of the tibia that received low energy ESWT. The clinical result was excellent and he was able to gradually return to sports activities.

Somatization Symptom and Steroid Myopathy in Cushing Syndrome with Adrenal Adenoma: A case report

We experienced musculoskeletal pain by somatization symptom and steroid myopathy in Cushing syndrome (adrenal adenoma) and hereby report this case. A 53-year old woman visited to clinic with chief complain of severe sole pain and tingling sensation (VAS 8.0) and multiple arthralgia (VAS 6.0) since 3 years ago. On examination, she showed severe depressive mood disorder, weakness of proximal limbs and other features of Cushing syndrome. The electromyelographic findings showed atypical type of myopathy without peripheral polyneuropathy. On laboratory examination, overnight and low dose dexamethasone suppression test was positive. The adrenal CT showed finding of left adrenal adenoma. After diagnosed of Cushing syndrome, laparoscopic adrenalectomy was done. The patient's severe pain and tingling sensation were immediately improved (VAS 3.0) concurrently with improvement of depressive mood following surgery. We concluded that the pain was originated from somatization symptom.

Molecular Mechanism of Insulin Resistance in Obesity and Type 2 Diabetes

Insulin resistance is a major risk factor for developing type 2 diabetes caused by the inability of insulin-target tissues to respond properly to insulin, and contributes to the morbidity of obesity. Insulin action involves a series of signaling cascades initiated by insulin binding to its receptor, eliciting receptor autophosphorylation and activation of the receptor tyrosine kinase, resulting in tyrosine phosphorylation of insulin receptor substrates (IRSs). Phosphorylation of IRSs leads to activation of phosphatidylinositol 3-kinase (PI3K) and, subsequently, to activation of Akt and its downstream mediator AS160, all of which are important steps for stimulating glucose transport induced by insulin. Although the mechanisms underlying insulin resistance are not completely understood in skeletal muscle, it is thought to result, at least in part, from impaired insulin-dependent PI3K activation and downstream signaling. This review focuses on the molecular basis of skeletal muscle insulin resistance in obesity and type 2 diabetes. In addition, the effects of insulin-sensitizing agent treatment and lifestyle intervention of human insulin-resistant subjects on insulin signaling cascade are discussed. Furthermore, the role of Rho-kinase, a newly identified regulator of insulin action in insulin control of metabolism, is addressed.

Treatment of Spontaneous Psoas Hematoma in a Hemiplegic Patient Undergoing Anticoagulation Therapy: case report

Spontaneous psoas hematoma in patients receiving anticoagulation therapy is a rare condition, but sometimes very serious even fatal, if not properly treated on time. One of our patients developed large spontaneous psoas hematoma while intensive rehabilitation therapy due to recent stroke with global aphasia and right hemiplegia. He had undergone anticoagulation therapy with warfarin and prothrombin time was within therapeutic range. Patient revealed sudden cold sweating with change of vital sign. Because of global aphasia, he could not explain subjective symptoms, but revealed rebound tenderness in right lower quadrant on physical examination. Emergency abdominal & pelvic CT scan showed large hematoma on right iliopsoas area with retroperitoneal extension. Because of unstable hemodynamics and high risks for surgery, transcatheter arterial emboilzation was recommended. Bleeding was controlled successfully after transcatheter arterial embolization, and vital sign was stabilized without other neurologic change.

The level of buccal gingival margin around single and two adjacent implant restorations: a preliminary result

STATEMENT OF PROBLEM: Little information is available about the buccal gingival level of multiple implant restorations. PURPOSE: This study was aimed to evaluate the relationship between width and height of buccal soft tissue around single and 2 adjacent implant restorations. MATERIAL AND METHODS: Four implant restoration groups (first and second molars, single second molars, posterior single restorations between teeth, and anterior single restorations between teeth) were randomly chosen from one dental institute. Each group comprised of 6 patients. After 6 months of function, silicone impressions were taken and stone models were fabricated for each restoration group. The stone models were cut in bucco-lingual direction at the most apical point of buccal gingival margin. The height and width of buccal supra-implant soft tissue were measured. One way ANOVA and Tukey HSD post hoc tests were performed to analyze the data obtained (P < .05). RESULTS: The most unfavorable width-height ratio was noted for the group, which was comprised of the second molar in the multiple adjacent (first and second molar) implant-supported restorations. The group also resulted in the shorter height of buccal supra-implant mucosa rather than that of anterior single implant restorations between natural teeth. CONCLUSION: To achieve a favorable level of buccal gingival margin, greater thickness of buccal supra-implant mucosa is required for the implant restorations without a neighboring natural tooth compared to the implant restorations next to a natural tooth.

Benign Metastasizing Leiomyoma of Lung / 대한흉부외과학회지

Benign metastasizing leiomyoma (BML) is a rare entity, characterized by the occurrence of multiple smooth muscle nodules in the lung with histologically benign leiomyoma. Both the uterine and pulmonary tumors have been found to express estrogen and progesterone receptors, which suggest that the pulmonary lesions represented metastases from leiomyoma. We experienced a 41-year-old female patient with BML and report here with the literature review.

Expression of Vascular Endothelial Growth Factor and Platelet-Derived Endothelial Cell Growth Factor in Head and Neck Squamous Cell Carcinoma and It's Relation to Angiogensis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Tumor angiogenesis is an essential process required for growth and metastasis in cancer. Vascular endothelial growth Factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) are known to be angiogenetic factors. The objectives of this study were to measure the expression of VEGF, PD-ECGF and microvessel density (MVD) in head and neck squamous cell carcinoma (HNSCC) and compare them to normal larynx. We also evaluated relationships of VEGF, PD-ECGF and MVD to clinicopathologic findings in HNSCC. MATERIAL AND METHODS: The expression of VEGF, PD-ECGF and MVD were evaluated by immunohistochemical staining of 26 cases of HNSCC and 6 cases of normal larynx. RESULTS: The expressions of VEGF, PD-ECGF and MVD in HNSCC were significantly higher than in the normal control (p<0.05). MVD were significantly correlated with VEGF and PD-ECGF expressions in HNSCC (p<0.05). The VEGF, PD-ECGF expression and MVD correlated with many clinicopathologic findings in HNSCC. CONCLUSION: These results suggest that VEGF and PD-ECGF are involved in angiogenesis and are related to clinicopathologic findings of HNSCC. Furthermore, we propose that expressions of VEGF, PD-ECGF and MVD to be investigated more in the future as prognostic indicators of HNSCC.

Correlation of Neuropeptide Y Neuron and its Size with Nitric Oxide Synthase in Cerebral Cortex of Aged Rats

No abstract available.