Effect of cerivastatin on proteinuria and urinary podocytes in patients with chronic glomerulonephritis.

BACKGROUND: We previously reported urinary podocytes to be a marker of glomerular injury. The aim of the present study was to determine whether cerivastatin, a newly developed, potent synthetic statin, affects proteinuria and urinary podocyte excretion in patients with chronic glomerulonephritis (CGN). METHODS: We randomly assigned 40 normotensive hypercholesterolemic patients with CGN to receive either cerivastatin 0.15 mg/day (n=20) or placebo (n=20). Subjects comprised 24 men and 16 women, with a mean age of 40.8+/-14.4 years; 27 had IgA nephropathy and 13 had non-IgA proliferative glomerulonephritis. Treatment was continued for 6 months. Plasma total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides, urinary protein excretion and the number of podocytes were measured before treatment and at 3 and 6 months after treatment. RESULTS: After 6 months, a significant reduction in total cholesterol (P<0.001), LDL-cholesterol (P<0.001) and triglycerides (P<0.05), and a significant increase in HDL-cholesterol (P<0.001) were observed in the group treated with cerivastatin. Urinary protein excretion decreased from 1.8+/-0.6 to 0.8+/-0.4 g/day, (P<0.01) in this group, and urinary podocyte excretion decreased from 1.6+/-0.6 to 0.9+/-0.4 cells/ml (P<0.01). However, placebo showed little effect on these lipid levels, urinary protein excretion and urinary podocyte excretion. The differences between the cerivastatin group and the placebo group were significant (cholesterol, P<0.001; LDL-cholesterol, P<0.001; triglycerides, P<0.05; HDL-cholesterol, P<0.001; urinary protein, P<0.01; and urinary podocytes, P<0.01). CONCLUSION: Statins such as cerivastatin may be beneficial for restoration of injured podocytes in patients with CGN and hypercholesterolaemia.     

Ketamine Suppresses Platelet Aggregation Possibly by Suppressed Inositol Triphosphate Formation and Subsequent Suppression of Cytosolic Calcium Increase

Background: Ketamine has been shown to suppress platelet aggregation, but its mechanisms of action have not been defined. The purpose of the current study is to clarify the effects of ketamine on human platelet aggregation and to elucidate the underlying mechanisms of its action.

Methods: Platelet aggregation was measured using an eight-channel aggregometer, and cytosolic free calcium concentration was measured in Fura-2/AM-loaded platelets using a fluorometer. Inositol 1,4,5-triphosphate (IP3) was measured with use of a commercially available IP3 assay kit. To estimate thromboxane A2 (TXA2) receptor binding affinity and expression, Scatchard analysis was performed using [3H]S145, a specific TXA2 receptor antagonist. TXA2 agonist binding assay was also performed. The membrane-bound guanosine 5'-triphosphatase activity was determined using [[gamma]-32P]guanosine triphosphate by liquid scintillation analyzer.

Results: Ketamine (500 [mu]m) suppressed aggregation induced by adenosine diphosphate (0.5 [mu]m), epinephrine (1 [mu]m), (+)-9,11-epithia-11,12-methano-TXA2 (STA2) (0.5 [mu]m), and thrombin (0.02 U/ml) to 39.1 +/- 30.9, 46.3 +/- 4.3, -2.0 +/- 16.8, and 86.6 +/- 1.4% of zero-control, respectively. Ketamine (250 [mu]m-1 mm) also suppressed thrombin- and STA2-induced cytosolic free calcium concentration increase dose dependently. Although ketamine (2 mm) had no effect on TXA2 receptor expression and its binding affinity, it (1 mm) suppressed intracellular peak IP3 concentrations induced by thrombin and STA2 from 6.60 +/- 1.82 and 4.39 +/- 2.41 to 2.41 +/- 0.98 and 1.90 +/- 0.86 pmol/109 platelets, respectively, and it suppressed guanosine triphosphate hydrolysis induced by thrombin (0.02 units/ml) and STA2 (0.5 [mu]m) to 50.3 +/- 3.2 and 67.5 +/- 5.5%versus zero-control, respectively.     

Glucagon acutely inhibits but chronically activates Na(+)/H(+) antiporter 3 activity in OKP cells.

BACKGROUND: We previously found that the Na(+)/H(+) exchanger 3 (NHE3) is localized in the apical membrane of the rat renal proximal tubule and thick ascending limb of Henle. In the present study, we examined the direct effect of glucagon on the opossum kidney P (OKP) cell Na(+)/H(+) antiporter, encoded by NHE3. METHODS: Na(+)/H(+) antiporter activity was measured as the rate of cell pH recovery from an acid load using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Northern blot and Western blot analyses were performed using OKP NHE3 cDNA and anti-OKP-NHE3 antibodies. RESULTS: Glucagon (1 ng/ml) acutely (1 h) inhibited, but chronically (24 h) activated NHE3 activity in OKP cells. These effects were blocked by either KT5720 or RpcAMP [protein kinase A (PKA) inhibitors], and mimicked by 10(-4) M dibutyryl-cAMP. Both NHE3 mRNA and protein abundance increased with the 24-hour incubation in glucagon or dibutyryl-cAMP. Cycloheximide did not prevent a significant increase in NHE3 activity at 24 h. We therefore examined NHE3 protein abundance in the surface membrane by the biotinylation method. cAMP or glucagon significantly increased NHE3 protein abundance in the surface membrane when incubated with cycloheximide for 24 h. CONCLUSIONS: Glucagon acutely inhibits but chronically activates NHE3 activity in OKP cells via a PKA-dependent pathway. Both protein-synthesis-dependent and -independent mechanisms play important roles in the chronic activation of NHE3.     

Surgical Resection of Hilar Cholangiocarcinoma: Analysis of Survival and Postoperative Complications

Background Surgery is the only potentially curative treatment for hilar bile duct cancer. This study sought to evaluate the efficacy and feasibility of surgical management of hilar bile duct carcinoma, including radical hepatectomy, at a single institution. Methods We performed a retrospective review of 49 consecutive patients who underwent surgery at our hospital between 1990 and 2003. Results Altogether, 44 of 49 patients underwent radical hepatectomy combined with caudate lobectomy and lymphadenectomy. One and four patients underwent partial hepatectomy or bile duct resection, respectively. No patients underwent preoperative portal vein embolization. The 5-year survival rate was 39.7%, with a median survival time of 3.75 years. The postoperative morbidity and mortality rates were 46.8% and 2.0%, respectively. Cox’s proportional hazard model revealed that lymph node status and the residual tumor factor were independent prognostic factors. Multivariate analysis revealed that preoperative hyperbilirubinemia, postoperative complications, and extended surgical procedures were independently associated with postoperative hyperbilirubinemia. After potentially curative resection, 39.4% of patients suffered from disease recurrence. In 60% of the total cases, the sites of recurrence were distant metastases. Conclusion Surgery, including radical hepatectomy combined with caudate lobectomy and lymph node dissection, is a feasible, effective treatment for hilar bile duct cancer.     

Enzymatic synthesis of no-carrier-added 6-[18F]fluoro-L-dopa with beta-tyrosinase.

An enzymatic synthesis of nca 6-[18F]fluoro-L-dopa has been developed. The process consists of a chemical synthesis of 4-[18F]fluorocatechol and its enzymatic reaction with beta-tyrosinase. The 4-[18F]fluorocatechol was prepared by nucleophilic aromatic substitution of the NO2 group on 6-nitroveratoraldehyde with [K/222]+18F-, followed by decarbonylation with tris(triphenylphosphine) rhodium(I) chloride and hydrolysis with hydroiodic acid. By C18 Sep-Pak purification, 4-[18F]fluorocatechol was obtained in ethanol with a radiochemical yield of 9.2%. An enzymatic reaction of 4-[18F]fluorocatechol, ammonium and pyruvate catalyzed by beta-tyrosinase in an ethanolic Tris-HCl buffer (pH 9.0) containing ascorbate gave within 5 min 6-[18F]fluoro-L-dopa with an approximate radiochemical yield of 60% without any isomers. The deproteinized reaction mixture was applied to a preparative reverse phase column, and the radiochemically and enantiomerically pure 6-[18F]fluoro-L-dopa was obtained with a radiochemical yield of 2.0% based on [18F]F- (decay-corrected). The synthesis time was 150 min from the EOB and the specific activity was > 200 GBq/micromol.     

Contemporary outcomes after superficial femoral artery angioplasty and stenting: the influence of TASC classification and runoff score

OBJECTIVE: A recent randomized trial suggested nitinol self-expanding stents (SES) were associated with reduced restenosis rates compared with simple percutaneous transluminal angioplasty (PTA). We evaluated our results with superficial femoral artery (SFA) SES to determine whether TransAtlantic InterSociety Consensus (TASC) classification, indication for intervention, patient risk factors, or Society of Vascular Surgery (SVS) runoff score correlated with patency and clinical outcome, and to evaluate if bare nitinol stents or expanded polytetrafluoroethylene (ePTFE) covered stent placement adversely impacts the tibial artery runoff. METHODS: A total of 109 consecutive SFA stenting procedures (95 patients) at two university-affiliated hospitals from 2003 to 2006 were identified. Medical records, angiographic, and noninvasive studies were reviewed in detail. Patient demographics and risk factors were recorded. Procedural angiograms were classified according to TASC Criteria (I-2000 and II-2007 versions) and SVS runoff scores were determined in every patient; primary, primary-assisted, secondary patency, and limb salvage rates were calculated. Cox proportional hazard model was used to determine if indication, TASC classification, runoff score, and comorbidities affected outcome. RESULTS: Seventy-one patients (65%) underwent SES for claudication and 38 patients (35%) for critical limb ischemia (CLI). Average treatment length was 15.7 cm, average runoff score was 4.6. Overall 36-month primary, primary-assisted, and secondary rates were 52%, 64%, and 59%, respectively. Limb salvage was 75% in CLI patients. No limbs were lost following interventions in claudicants (mean follow-up 16 months). In 24 patients with stent occlusion, 15 underwent endovascular revision, only five (33%) ultimately remained patent (15.8 months after reintervention). In contrast, all nine reinterventions for in-stent stenosis remained patent (17.8 months). Of 24 patients who underwent 37 endovascular revisions for either occlusion or stenosis, eight (35%) had worsening of their runoff score (4.1 to 6.4). By Cox proportional hazards analysis, hypertension (hazard ratio [HR] 0.35), TASC D lesions (HR 5.5), and runoff score > 5 (HR 2.6) significantly affected primary patency. CONCLUSIONS: Self-expanding stents produce acceptable outcomes for treatment of SFA disease. Poorer patency rates are associated with TASC D lesions and poor initial runoff score; HTN was associated with improved patency rates. Stent occlusion and in-stent stenosis were not entirely benign; one-third of patients had deterioration of their tibial artery runoff. Future studies of SFA interventions need to stratify TASC classification and runoff score. Further evaluation of the long-term effects of SFA stenting on tibial runoff is needed.     

Three cases of small cell carcinoma of the urinary bladder: a case report

We report three cases of small cell carcinoma of the urinary bladder. Case 1: A 69-year-old man showed microscopic hematuria during follow up of prostate cancer of stage D2. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage of pT2N0M0. Complete remission was achieved by three courses of chemotherapy consisting of irinotecan and carboplatin. The patient was died by prostate cancer 16 months after the chemotherapy. Case 2: An 83-year-old woman presented with macroscopic hematuria. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage of pT2N0M0 and partial cystectomy was performed. The patient has been alive without any evidence of tumor recurrence at 6 months after surgery. Case 3: An 84-year-old man presented with macroscopic hematuria. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage ofcT3bN0M1 with multiple liver metastases. Complete remission was achieved by three courses of chemotherapy consisting of etoposide and carboplatin.     

Correlation between Hydroxyapatite Crystallite Orientation and Ultrasonic Wave Velocities in Bovine Cortical Bone

The mineral component of bone is mainly composed of calcium phosphate, constituting 70% of total bone mass almost entirely in the form of hydroxyapatite (HAp) crystals. HAp crystals have a hexagonal system and uniaxial elastic anisotropy. The objective of this study was to investigate the effect of HAp crystallite preference on macroscopic elasticity. Ultrasonic longitudinal wave velocity and the orientation of HAp crystallites in bovine cortical bone are discussed, considering microstructure, density, and bone mineral density (BMD). Eighty cube samples of cortical bone were made from two bovine femurs. The orientation of HAp crystallites was evaluated by integrated intensity ratio of (0002) peak using an X-ray diffractometer. Ultrasonic longitudinal wave velocity was investigated with a conventional pulse system. The intensity ratio of HAp crystallites and velocity were measured in three orthogonal directions; most HAp crystallites aligned in the axial direction of the femurs. Our results demonstrate a linear correlation between velocity and intensity ratio in the axial direction. Significant correlation between velocity and BMD values was observed; however, the correlation disappeared if we focused on the identical type of microstructure. In conclusion, differences in microstructure type have an impact on density and BMD, which clearly affects the velocity. In addition, at the nanoscopic level, HAp crystallites aligned in the axial direction also affected the velocity and anisotropy.     

Pulmonary infarction caused by the spontaneous migration of the vena caval tumor thrombus of right renal cell carcinoma: a case report]

A 70-year-old male with right renal mass incidentally found by annual check-up using ultrasound, was referred to Department of Urology, Jikei University Affiliated Kashiwa Hospital. He was diagnosed as having right renal cell carcinoma with vena caval tumor thrombus extending above the diaphragm (T3c) preoperatively. The day before the scheduled day of operation, right pulmonary infarction caused by spontaneous migration of vena caval tumor thrombus of right renal cell carcinoma developed. Although arterial blood gas findings were poor, he only had low grade chest pain without shock. Therefore, we successfully performed right radical nephrectomy and thrombectomy of right pulmonary artery the next day. He was discharged 42 days postoperatively, but, he died from acute heart failure 9 months after the operation.