Wnt signaling in liver regeneration, disease, and cancer

The liver exhibits the highest recovery rate from acute injuries. However, in chronic liver disease, the long-term loss of hepatocytes often leads to adverse consequences such as fibrosis, cirrhosis, and liver cancer. The Wnt signaling plays a pivotal role in both liver regeneration and tumorigenesis. Therefore, manipulating the Wnt signaling has become an attractive approach to treating liver disease, including cancer. Nonetheless, given the crucial roles of Wnt signaling in physiological processes, blocking Wnt signaling can also cause several adverse effects. Recent studies have identified cancer-specific regulators of Wnt signaling, which would overcome the limitation of Wnt signaling target approaches. In this review, we discussed the role of Wnt signaling in liver regeneration, precancerous lesion, and liver cancer. Furthermore, we summarized the basic and clinical approaches of Wnt signaling blockade and proposed the therapeutic prospects of cancer-specific Wnt signaling blockade for liver cancer treatment.

Ultrasonographic Diagnosis of the Knee

Knee ultrasonography is a feasible and useful diagnostic method not only for the evaluation of periarticular soft tissues but also for intra-articular lesions and for the diagnosis of tumorous disease. Joint effusion, synovial thickening, intra-articular loose bodies, bursal and/or other fluid collection, ganglionic cysts, ligament and tendon injuries, tendinosis, osteomyelitis, and symptoms related to metallic hardware can be diagnosed using ultrasonography.

Icodextrin Improves the Serum Potassium Profile with the Enhancement of Nutritional Status in Continuous Ambulatory Peritoneal Dialysis Patients

The impact of glucose-free icodextrin (ID) for overnight dwell as compared to conventional glucose-containing dialysate (GD) on potassium (K+) metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients has not yet been investigated. Serum K+ in a total of 255 stable patients (116 on GD and 139 on ID) on CAPD for more than 6 months and in 139 patients on ID before and after ID use (Pre-ID and Post-ID) were observed along with nutritional markers in a 2-year study period (Jan. 2006 to Dec. 2007). The prevalence of hypokalemia was similar between patients on GD and ID (16.7% vs 17.3%), but was lower on Post-ID than Pre-ID (17.3% vs 20.5%) without statistic significance. The mean serum K+ level was higher on ID than on GD (P<0.05) as well as Post-ID than Pre-ID (P<0.001). In the multivariate analysis, serum K+ levels were positively correlated with serum albumin, and creatinine in all patients (P<0.05), and ID-use in younger patients (age< or =56, P<0.001). Serum albumin, creatinine, total CO2, and body mass index were significantly higher on Post-ID than Pre-ID. Icodextrin dialysate for chronic overnight dwell could increase serum K+ levels and lower the prevalence of hypokalemia compared to conventional glucose-containing dialysate. The improved chronic K+ balance in CAPD patients on icodextrin could be related to enhanced nutritional status rather than its impact on acute intracellular K+ redistribution.

Recurrent Symptomatic Hyperglycemia on Maintenance Hemodialysis is not Necessarily Related to Hypertonicity: A Case Report

On view of the absent or minimal osmotic diuresis in end stage renal disease, hyperglycemia on maintenance hemolysis as compared to nonketotic hyperosmolar status without underlying advanced renal failure has been noted to show a wide clinical spectrum form severe manifestations by hypertonicity to no clinical manifestations at all. We experienced a 60-year-old man with a known history of type 2 diabetes mellitus on maintenance hemodialysis for 2 years, who was admitted 4 times within 1 year with hyperglycemia (>500 mg/dL) accompanied by recurrent nausea and vomiting at each admission. However, the calculated effective osmolality (tonicity) in this case ranged only from 286 to 303 mOsm/kg H2O. During the past 6 months following meticulous education for the importance of compliance to medication, especially prokinetics for diabetic gastroparesis, he developed no further episode of hyperglycemia or nausea and vomiting.

A Case of Sustained Hypoglycemia due to Nateglinide in a Maintenance Hemodialysis Patient / 대한신장학회지

The risk of development of hypoglycemia increases during glycemic control in end-stage renal disease (ESRD) patients. We report the case that an ESRD patient on maintenance hemodialysis has experienced sustained hypoglycemia with a nateglinide. A 73-year old male ESRD patient on hemodialysis was admitted with exertional dyspnea and increased liver function test. On the 4th day after admission, he had mental change with his blood glucose level of 41 mg/dL. His mental state improved promptly after intravenous injection of 25 g of glucose. To prevent rebound hypoglycemia 10% glucose solution was continuously infused and nateglinide was discarded. However, he has had recurrent hypoglycemic attacks until the 6th day after admission, and thereafter there was no further hypoglycemic attack. On the 5th day of admission, when there was second hypoglycemic attack, the fasting insulin level was 31.62 U/mL, indicating that hypoglycemia was accompanied by insulin hypersecretion. In conclusion, we suggest that nateglinide may provoke a severe and sustained hypoglycemia in an ESRD patient on maintenance hemodialysis and its use might be avoided.

Add-on Therapy of Potassium-exchange Resin for Hrkalemia in Chronic Kidney Disease Patients on Renin-angiotensin System Blockers / 대한신장학회지

PURPOSE: This prospective study aimed to evaluate the safety and efficacy of potassium-exchange resin (PER, Kalimate(R) or Argamate(R)) for managing hyperkalemia induced by Renin-Angiotensin System (RAS) blockers in chronic kidney disease (CKD) patients without their discontinuation. METHODS: Besides conservative remedies including low-potassium diet, all hyperkalemic CKD patients (n=21, [K] > or =5.6 mEq/L) received PER added on angiotensin-converting enzyme inhibitor (Moexipril, n=2) or angiotensin-receptor blocker (Irbesartan, n=19) with, at least, weekly monitoring of serum [K] if its level remains more than 5.5 mEq/L for more than 2 months (mean+/-SD, 6.8+/-5.9 mon; range, 2-26 mon). RESULTS: Baseline serum [K] on RAS blocker alone (5.1+/-0.4 mEq/L; 4.2-6.3 mEq/L) increased to 6.0 +/-0.4 mEq/L (p<0.05) before adding PER, and then it was significantly decreased to 5.3+/-0.6 mEq/L at the first clinic visit (p<0.05) and to 5.0+/-0.7 mEq/L at the last clinic visit (p<0.05) following the administration of PER added on RAS blocker. During the study period, GFR, serum creatinine and urinary protein excretion didn't change significantly. CONCLUSION: The development of hyperkalemia on RAS blockers in CKD patients doesn't necessarily lead to withdrawal of RAS blockers when the cautious add-on therapy of potassium-exchange resin with other conservative remedies launches, unless severe refractory hyperkalemia persists.

Propylthiouracil-associated p-ANCA Positive Vasculitis with Focal Segmental Glomerulosclerosis / 대한신장학회잡지

Antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis has been reported in Graves' disease patients treated with propylthiouracil (PTU). In most cases, it's renal involvements has been known as crescentic glomerulonephritis. A 41-year-old female patient with hyperthyroidism has been treated with PTU for 3 years. The patient had developed isolated hematuria and polyarthralgia with p-ANCA positivity, 6 months and 10 months after PTU treatment, respectively. She had been continuously treated with PTU until she was admitted at our hospital. Three months before admission, polyarthralgia was aggravated and purpura in both lower legs and hands was developed. Urinalysis revealed hematuria, proteinuria. Serologic evaluation showed p-ANCA positive. Skin biopy showed leukocytoclastic vasculitis and renal biopsy showed focal segmental glomerulosclerosis (FSGS). She was diagnosed as PTU-associated vasculitis with FSGS. Polyarthralgia and purpura were improved after discontinuing the PTU with prednisolone treatment but hematuria, proteinuria were not changed. We suggest that progression of PTU-associated focal segmental necrotizing glomerulonephritis to FSGS over two years might be due to continued PTU medication.

Outbreak of Hepatitis by Orientia tsutsugamushi in the Early Years of the New Millenium / 대한간학회지

BACKGROUND/AIMS: Orientia -tsutsugamushi infection is an acute febrile disease due to the accidental transmission through human skin of forest dwelling vector Leptotrombidium larva. The authors observed liver dysfunctions in patients diagnosed with tsutsugamushi disease (Scrub typhus) in the past 3 years and report the data in the hope of bringing attention to this disease in the differential diagnosis of autumn-season hepatitis, especially of non-A, non-B and non-C hepatitis. METHODS: Medical records of 22 patients diagnosed with tsutsugamushi disease by the hemagglutinin method between October 2000 and November 2002 were reviewed. RESULTS: Female gender was dominant in the ratio of 3.4:1. Mean age was 56.4 +/- 2.6. Admission was between 23rd September and 15th November with the peak between mid October and early November. Fever, being the most common symptom, was observed in 21 cases, myalgia in 13, arthralgia in 12, chills in 6, and skin rash in 6. An incubation period of 7-9 days was most common (10 cases), 13-15 days (4), 10-12 days (3), within 3 days (3), and 4-6 days (2). Average ALT, AST and GGTP were increased to 93.2 +/- 17.3 IU/L (18 +/- 345 IU/L), 92.5 +/- 11.7 IU/L (34-255 IU/L) and 132.2 +/- 14.5 IU/L (19-251 IU/L), respectively, but total bilirubin was normal. All the patients improved with doxycycline therapy. CONCLUSIONS: Since it usually shows liver dysfunction, it is important to take Orientia tsutsugamushi into consideration in differential diagnosis of autumn-season, febrile hepatic disease.