Cyclic adenosine monophosphate (cAMP) signaling is critical for regulating metabolic homeostasis in mammals. In particular, transcriptional regulation by cAMP response element-binding protein (CREB) and its coactivator, CREB-regulated transcription coactivator (CRTC), is essential for controlling the expression of critical enzymes in the metabolic process, leading to more chronic changes in metabolic flux. Among the CRTC isoforms, CRTC2 is predominantly expressed in peripheral tissues and has been shown to be associated with various metabolic pathways in tissue-specific manners. While initial reports showed the physiological role of CRTC2 in regulating gluconeogenesis in the liver, recent studies have further delineated the role of this transcriptional coactivator in the regulation of glucose and lipid metabolism in various tissues, including the liver, pancreatic islets, endocrine tissues of the small intestines, and adipose tissues. In this review, we discuss recent studies that have utilized knockout mouse models to delineate the role of CRTC2 in the regulation of metabolic homeostasis.

Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.
Acetyl Coenzyme A/metabolism ; Fatty Acids/metabolism ; Fatty Liver/*metabolism/pathology ; Humans ; Lipogenesis ; Mitochondria/metabolism ; Triglycerides/metabolism

Purpose: Compressive hip dressings have been used to decrease the amount of postoperative bleeding after total hiparthroplasty. However, there is no data showing that a compressive dressing is effective. This study evaluated the effect of compressive dressings on the level of postoperative bleeding after total replacement arthroplasty. Materials and Methods: This prospective randomized clinical trail included 80 consecutive primary total hip arthroplasties in 72 patients. The 80 hips were randomly assigned to a compressive dressing group or a non-compressive dressing group using a table of random numbers. Forty-two hips in 37 patients were treated using the compressive dressing and the remaining 38 hips in 35 patients were treated using a non-compressive dressing. The patients were followed up for an average of 10.3 months. In all patients, a hemovac suction drain was inserted postoperatively. Results: The mean level of bleeding was 626.6 mL in the compressive group and 693.8 mL in the non-compressive group. There was no statistical difference between the two groups (P=0.416). Moreover, the incidence of postoperative complications including dislocation, nerve injury, symptomatic deep vein thrombosis and heterotopic ossification was similar in both groups. Conclusion: These results suggest that the compressive dressing has no significant effect on the amount of postoperative bleeding and clinical results after total hip arthroplasty.
Arthroplasty* ; Arthroplasty, Replacement ; Arthroplasty, Replacement, Hip* ; Bandages ; Dislocations ; Hemorrhage* ; Hip ; Humans ; Incidence ; Ossification, Heterotopic ; Postoperative Complications ; Prospective Studies ; Suction ; Venous Thrombosis

During fasting periods, hepatic glucose production is enhanced by glucagon to provide fuels for other organs. This process is mediated via cAMP-dependent induction of the CREB regulated transcriptional coactivator (CRTC) 2, a critical transcriptional activator for hepatic gluconeogenesis. We have previously shown that CRTC2 activity is regulated by AMP activated protein kinase (AMPK) family members. Here we show that adiponectin and thiazolidinedione directly regulate AMPK to modulate CRTC2 activity in hepatocytes. Adiponectin or thiazolidinedione lowered glucose production from primary hepatocytes. Treatment of both reagents reduced gluconeogenic gene expression as well as cAMP-mediated induction of CRE reporter, suggesting that these reagents directly affect CREB/CRTC2- dependent transcription. Furthermore, adiponectin or thiazolidinedione mediated repression of CRE activity is largely blunted by co-expression of phosphorylation defective mutant CRTC2, underscoring the importance of serine 171 residue of this factor. Taken together, we propose that adiponectin and thiazolidinedione promote the modulation of AMPK-dependent CRTC2 activity to influence hepatic gluconeogenesis.
Adiponectin/*pharmacology ; Animals ; Cells, Cultured ; *Gene Expression Regulation ; Gluconeogenesis/*drug effects ; Glucose/metabolism ; Hepatocytes/drug effects/*metabolism ; Humans ; Liver/cytology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Protein Kinases/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Thiazolidinediones/*pharmacology ; Transcription Factors/genetics/*metabolism

Glucose homeostasis is tightly controlled by the regulation of glucose production in the liver and glucose uptake into peripheral tissues, such as skeletal muscle and adipose tissue. Under prolonged fasting, hepatic gluconeogenesis is mainly responsible for glucose production in the liver, which is essential for tissues, organs, and cells, such as skeletal muscle, the brain, and red blood cells. Hepatic gluconeogenesis is controlled in part by the concerted actions of transcriptional regulators. Fasting signals are relayed by various intracellular enzymes, such as kinases, phosphatases, acetyltransferases, and deacetylases, which affect the transcriptional activity of transcription factors and transcriptional coactivators for gluconeogenic genes. Protein arginine methyltransferases (PRMTs) were recently added to the list of enzymes that are critical for regulating transcription in hepatic gluconeogenesis. In this review, we briefly discuss general aspects of PRMTs in the control of transcription. More specifically, we summarize the roles of four PRMTs: PRMT1, PRMT 4, PRMT 5, and PRMT 6, in the control of hepatic gluconeogenesis through specific regulation of FoxO1- and CREB-dependent transcriptional events.
Acetyltransferases ; Adipose Tissue ; Arginine* ; Brain ; Erythrocytes ; Fasting ; Gluconeogenesis ; Glucose* ; Homeostasis ; Liver ; Metabolism* ; Methyltransferases* ; Muscle, Skeletal ; Phosphoric Monoester Hydrolases ; Phosphotransferases ; Protein-Arginine N-Methyltransferases ; Transcription Factors

BACKGROUND: To identify the prevalence and risk factors of poststroke depression(PSD) in patients admitted to department of rehabilitation medicine after stroke, to compare functional recovery of depressed patients and that of non-depressed patients, and to recognize the most useful depression scale that can predict functional recovery. METHOD: Of the hospitalized stroke patients in the department of Rehabilitation Medicine, 24 patients who were communicable were included in this study. To evaluate PSD, Beck depression inventory(BDI) and Korean form of Geriatric depression scale(KGDS) were used as self-rating scales. Hamilton depression scale(HAM-D) was used as an objective scale. Functional Independence measure(FIM) was measured at admission and discharge to evaluate functional recovery. RESULTS: In the 24 subjects, 17 patients(70.8%) and 9 patients(37.5%) were depressive by BDI and HAM-D. Of the 19 elderly patients, 16(84.2%) were depressive by KGDS. Factors such as age, level of education, religion, etiology or location of stroke were not significantly associated with PSD. And FIMscores were not significantly different in the depressed patients and non-depressed patients. The correlation coefficients of BDI, KGDS, HAM-D and FIMgain or efficiency were not statistically significant. CONCLUSION: The prevalence of PSDwas high in our study, but no association was found between PSD and functional recovery.
Aged ; Depression* ; Education ; Hip* ; Humans ; Inpatients* ; Prevalence ; Rehabilitation* ; Risk Factors ; Stroke ; Weights and Measures

Purpose: We evaluated the results of cementless acetabular revisions performed with morselized bone grafting and screw-fixed hemispherical cups with different surface treatments. Materials and Methods: Forty hips, which had been followed for more than 10 years, were included in this study. Reconstruction was performed with 10 hydroxyapatite (HA)-coated cups and 30 porocoated ones. The mean followup time was 12 years and 1 months (range, 10 years to 15 years). Re-revision or radiographic loosening was considered as an endpoint of follow-up. Results: The average Harris hip score improved from 52 points to 75 points. During the follow-up period, radiographic loosening was observed in 17 hips. The loosened implants were HA-coated cups in 8 hips and porocoated ones in 9 hips. In 14 of these, re-revision of the cups was performed. The re-revision rate was 20% for the porocoated cups and 80% for the HA-coated cups. There were 2 hips with liner wear, which had undergone liner and head changes. Bone grafts were united in all the hips. The average time to union was 5.2 months (range, 2 to 9 months), and the average time to incorporation was 12 months (range, 5 to 18 months). Conclusion: Our results imply that HA-coated cups have a significantly higher failure rate compared with the porocoated ones (P<0.05) after a minimum follow-up of 10 years. Morselized bone grafting with use of a porocoated cup is an effective modality, which can restore the bone loss of the acetabulum in revision total hip arthroplasty.
Acetabulum* ; Arthroplasty, Replacement, Hip ; Bone Transplantation ; Durapatite ; Follow-Up Studies* ; Head ; Hip ; Transplants

Spasticity is common stroke in patients, and its management has been considered as one of the major problems in stroke rehabilitation. The goal of this study was to determine if transcutaneous electrical nerve stimulation(TENS) and acupuncture would reduce the muscle spasticity. To estimate the efficacy of electrical stimulation for the treatment of spasticity TENS(100 Hz, asymmetric bipolar pulse current) was applied to the skin over the extensor muscles of spastic limbs for 20 minutes, once a day in six stroke patients. In addition, acupuncture was also applied to the acupoints of extensor muscles of all extremities and face for 20 minutes twice a day to determine the efficacy of acupuncture for the treatment of spasticity in six stroke patients. As controls subjects, six stroke patients were examined without TENS or acupuncture treatment. In experimental groups, the efficacy of treatment was measured 1, 5, 10, 15 days and 20 days after treatment with either TENS or acupuncture using the spasticity measurement methods (modified Ashworth scale, ankle clonus score, and H/M ratio). Based on the results from the present study, we have concluded that the H/M ratios of affected spastic limbs were significantly higher than those of unaffected limbs (p<0.05). TENS and acupuncture therapies lessened the spasticity of affected limbs of stroke patients when measured with the modified Ashworth scale however not with the H/M ratios nor with the ankle clonus scores.
Acupuncture Points ; Acupuncture* ; Ankle ; Electric Stimulation ; Extremities ; Humans ; Muscle Spasticity ; Muscles ; Rehabilitation ; Skin ; Stroke* ; Transcutaneous Electric Nerve Stimulation*