Publications

Leptin regulates energy balance. However, knowledge of the critical intracellular transducers of leptin signaling remains incomplete. We found that Rho-kinase 1 (ROCK1) regulates leptin action on body weight homeostasis by activating JAK2, an initial trigger of leptin receptor signaling. Leptin promoted the physical interaction of JAK2 and ROCK1, thereby increasing phosphorylation of JAK2 and downstream activation of Stat3 and FOXO1. Mice lacking ROCK1 in either pro-opiomelanocortin (POMC) or agouti-related protein neurons, mediators of leptin action, displayed obesity and impaired leptin sensitivity. In addition, deletion of ROCK1 in the arcuate nucleus markedly enhanced food intake, resulting in severe obesity. Notably, ROCK1 was a specific mediator of leptin, but not insulin, regulation of POMC neuronal activity. Our data identify ROCK1 as a key regulator of leptin action on energy homeostasis.

OBJECTIVE: The aims of this study were to investigate the long-term effect of complex decongestive therapy (CDT) on lymphedema volume reduction, especially considering the proximal and distal parts of the leg, and to evaluate the utility of pre-therapy lymphoscintigraphy in predicting the response to CDT in patients with lower-limb lymphedema after surgery for gynecologic cancer.

METHODS: Medical records of 158 patients with secondary lymphedema of unilateral leg after surgery for gynecological cancer were reviewed retrospectively. They were treated with two weeks of CDT along with self-administered home therapy and were followed up for 24 months. Whole, proximal and distal leg volume was serially measured by using an optoelectric volumeter prior to and immediately after therapy, and follow-up visits at months 3, 6, 12 and 24. Lymphoscintigraphy was performed prior to therapy.

RESULTS: The percent volume reduction was 22.1% in the whole leg, 30.9% in the distal leg and 18.4% in the proximal leg immediately after CDT. The volume reduction was maintained for 24 months, but the distal leg was significantly well maintained better than the proximal leg. Extremity radioisotope uptake ratio (EUR) among lymphoscintigraphic findings could predict the improvement of lymphedema volume in the distal, proximal and whole leg.

CONCLUSIONS: This study suggests that the long-term edema reducing effects of CDT are better maintained in the distal leg than in the proximal part, and initial lymphoscintigraphic quantitative finding may usefully predict the short and long-term response to CDT.

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.

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.