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Publications (112)377.32 Total impact
Article: Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients[Show abstract] [Hide abstract]
ABSTRACT: In recent times, therapy for renal anemia has changed dramatically in that iron administration has increased and doses of erythropoiesis-stimulating agents (ESAs) have decreased. Here we used a prospective, observational, multicenter design and measured the serum ferritin and hemoglobin levels every 3 months for 2 years in 1086 patients on maintenance hemodialysis therapy. The associations of adverse events with fluctuations in ferritin and hemoglobin levels and ESA and iron doses were measured using a Cox proportional hazards model for time-dependent variables. The risks of cerebrovascular and cardiovascular disease (CCVD), infection, and hospitalization were higher among patients who failed to maintain a target-range hemoglobin level and who exhibited high-amplitude fluctuations in hemoglobin compared with patients who maintained a target-range hemoglobin level. Patients with a higher compared with a lower ferritin level had an elevated risk of CCVD and infectious disease. Moreover, the risk of death was significantly higher among patients with high-amplitude ferritin fluctuations compared with those with a low ferritin level. The risks of CCVD, infection, and hospitalization were significantly higher among patients who were treated with high weekly doses of intravenous iron compared with no intravenous iron. Thus, there is a high risk of death and/or adverse events in patients with hemoglobin levels outside the target range, in those with high-amplitude hemoglobin fluctuations, in those with consistently high serum ferritin levels, and in those with high-amplitude ferritin fluctuations.Kidney International advance online publication, 23 April 2014; doi:10.1038/ki.2014.114.Kidney International 04/2014; 86(4). DOI:10.1038/ki.2014.114 · 8.52 Impact Factor
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ABSTRACT: CKD progresses with fibrosis and erythropoietin (Epo)-dependent anemia, leading to increased cardiovascular complications, but the mechanisms linking Epo-dependent anemia and fibrosis remain unclear. Here, we show that the cellular phenotype of renal Epo-producing cells (REPs) alternates between a physiologic Epo-producing state and a pathologic fibrogenic state in response to microenvironmental signals. In a novel mouse model, unilateral ureteral obstruction-induced inflammatory milieu activated NFκB and Smad signaling pathways in REPs, rapidly repressed the Epo-producing potential of REPs, and led to myofibroblast transformation of these cells. Moreover, we developed a unique Cre-based cell-fate tracing method that marked current and/or previous Epo-producing cells and revealed that the majority of myofibroblasts are derived from REPs. Genetic induction of NFκB activity selectively in REPs resulted in myofibroblastic transformation, indicating that NFκB signaling elicits a phenotypic switch. Reversing the unilateral ureteral obstruction-induced inflammatory microenvironment restored the Epo-producing potential and the physiologic phenotype of REPs. This phenotypic reversion was accelerated by anti-inflammatory therapy. These findings demonstrate that REPs possess cellular plasticity, and suggest that the phenotypic transition of REPs to myofibroblasts, modulated by inflammatory molecules, underlies the connection between anemia and renal fibrosis in CKD.Journal of the American Society of Nephrology 07/2013; DOI:10.1681/ASN.2013010030 · 9.47 Impact Factor
Article: A Small Molecule Inhibitor to Plasminogen Activator Inhibitor 1 Inhibits Macrophage Migration[Show abstract] [Hide abstract]
ABSTRACT: OBJECTIVE: Macrophage (Mϕ) migration rests on the adhesion/detachment between Mϕ surface components and extracellular matrixes, and the contribution of numerous inflammatory disorders. Plasminogen activator inhibitor (PAI)-1, a serine protease inhibitor, influences Mϕ motility through an action distinct from its classical modulation of the plasmin-based fibrinolytic process. We rely here on a small molecule PAI-1 inhibitor (TM5275) to investigate the role of PAI-1 in Mϕ migration in the pathogenesis of renal injury.Approach and Results-Mϕ migration was inhibited both in vitro and in vivo by TM5275. It was also reduced in T-cell-deficient nude mice, but not in PAI-1-deficient mice. Mϕ migration hinged on the interaction of PAI-1 with low-density lipoprotein receptor-related protein, an interaction prevented by TM5275, but not with vitronectin, urokinase-type plasminogen activator, or tissue-type plasminogen activator. Fed to rats with anti-Thy-1-induced nephritis, TM5275 significantly decreased Mϕ accumulation and ameliorated the progression of renal injury. CONCLUSIONS: These findings suggest that a small molecule PAI-1 inhibitor represents a novel class of anti-inflammatory agents targeting Mϕ migration by the inhibition of the interaction of PAI-1 with low-density lipoprotein receptor-related protein.Arteriosclerosis Thrombosis and Vascular Biology 03/2013; 33(5). DOI:10.1161/ATVBAHA.113.301224 · 6.34 Impact Factor
Article: Japan Renal Biopsy Registry and Japan Kidney Disease Registry: Committee Report for 2009 and 2010.[Show abstract] [Hide abstract]
ABSTRACT: The Japan Renal Biopsy Registry (J-RBR) was started in 2007 and the Japan Kidney Disease Registry (J-KDR) was then started in 2009 by the Committee for Standardization of Renal Pathological Diagnosis and the Committee for the Kidney Disease Registry of the Japanese Society of Nephrology. The purpose of this report is to describe and summarize the registered data from 2009 and 2010. For the J-KDR, data were collected from 4,016 cases, including 3,336 (83.1 %) by the J-RBR and 680 (16.9 %) other cases from 59 centers in 2009, and from 4,681 cases including 4,106 J-RBR cases (87.7 %) and 575 other cases (12.3 %) from 94 centers in 2010, including the affiliate hospitals. In the J-RBR, 3,165 native kidneys (94.9 %) and 171 renal grafts (5.1 %) and 3,869 native kidneys (94.2 %) and 237 renal grafts (5.8 %) were registered in 2009 and 2010, respectively. Patients younger than 20 years of age comprised 12.1 % of the registered cases, and those 65 years and over comprised 24.5 % of the cases with native kidneys in 2009 and 2010. The most common clinical diagnosis was chronic nephritic syndrome (55.4 % and 50.0 % in 2009 and 2010, respectively), followed by nephrotic syndrome (22.4 % and 27.0 %); the most frequent pathological diagnosis as classified by the pathogenesis was IgA nephropathy (31.6 % and 30.4 %), followed by primary glomerular diseases (except IgA nephropathy) (27.2 % and 28.1 %). Among the primary glomerular diseases (except IgA nephropathy) in the patients with nephrotic syndrome, membranous nephropathy was the most common histopathology in 2009 (40.3 %) and minor glomerular abnormalities (50.0 %) were the most common in 2010 in native kidneys in the J-RBR. Five new secondary and longitudinal research studies by the J-KDR were started in 2009 and one was started in 2010.Clinical and Experimental Nephrology 02/2013; DOI:10.1007/s10157-012-0746-8 · 1.71 Impact Factor
Internal Medicine 01/2013; 52(17):1853. DOI:10.2169/internalmedicine.52.0973 · 0.97 Impact Factor
Article: Beneficial role of tolvaptan in the control of body fluids without reductions in residual renal function in patients undergoing peritoneal dialysis.[Show abstract] [Hide abstract]
ABSTRACT: The V2 receptor antagonist tolvaptan has been approved for volume control in heart-failure patients in Japan. Tolvaptan increases renal blood flow, and so the present study was designed to ascertain whether tolvaptan could be a useful diuretic for volume control without reducing residual renal function (RRF) in peritoneal dialysis (PD) patients. Tolvaptan was administered in 15 PD patients (15 mg daily). Urine volume, body weight, and blood pressure were monitored Urinary excretion of urea nitrogen Na+, the osmolality of plasma and urine, and peritoneal and renal Kt/V were analyzed before and after tolvaptan treatment. In 11 of 15 patients, urine volume increased to more than 400 mL daily. A significant increase in diluted urine was observed, as indicated by a reduction in the specific gravity or osmolality of urine (or both). Urinary excretion of urea nitrogen, and Na+ was significantly increased Increases in renal Kt/V were observed, but peritoneal Kt/V was unchanged. Singnificant increase in creatinine clearance was also observed These data suggest that tolvaptan not only stimulates water diuresis, but also natriuresis, without reducing RRF in PD patients. Hence, tolvaptan could be a beneficial tool for the control of body fluid and maintenance of RRF in PD patients.Advances in peritoneal dialysis. Conference on Peritoneal Dialysis 01/2013; 29:33-7.
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ABSTRACT: BACKGROUND: Excess fluid distribution is a common disorder in peritoneal dialysis (PD) patients. Tacrolimus malabsorption may also occur in PD patients, and may lead to acute allograft rejection after transplantation. The purpose of this study was to evaluate the relationship between tacrolimus pharmacokinetics and excess fluid distribution according to pre-transplant dialysis modality. METHODS: We retrospectively analyzed 41 adult living-donor kidney transplantations, including nine PD patients and 32 hemodialysis (HD) patients. We examined tacrolimus pharmacokinetics in the peri-operative period and determined the association between the tacrolimus absorption rate and body weight reduction. The absorption efficacy of tacrolimus was evaluated as the dose-normalized tacrolimus absorption rate. Tacrolimus concentrations in PD effluent were measured by high-performance liquid chromatography. RESULTS: The tacrolimus absorption rate on the day before kidney transplantation tended to be lower in PD patients than in HD patients; however, the rate improved after kidney transplantation and was similar in both groups of patients. The peak tacrolimus concentration time was later in PD patients than in HD patients. The body weight reduction after kidney transplantation was greater in PD patients than in HD patients, and was significantly associated with the change in tacrolimus absorption rate (p = 0.04, r = 0.32). Only 0.002 % of the oral tacrolimus dose was removed by PD itself. CONCLUSION: Excess fluid distribution in PD patients appears to contribute to tacrolimus malabsorption rather than PD itself. We should consider the risk of tacrolimus malabsorption in patients with possible excess fluid distribution, particularly in PD patients.Clinical and Experimental Nephrology 12/2012; 17(5). DOI:10.1007/s10157-012-0764-6 · 1.71 Impact Factor
Article: Renal disease in the elderly and the very elderly Japanese: analysis of the Japan Renal Biopsy Registry (J-RBR).[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND AND OBJECTIVES: Data regarding renal disease in the elderly (age ≥65 years old) and very elderly (age ≥80 years old) Japanese are extremely limited. The aim of this study was to examine the causes of renal disease and their clinical presentations in elderly patients who underwent renal biopsy. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: From July 2007 to November 2011, all of the elderly native renal biopsy patients who had been registered in the Japan Renal Biopsy Registry (J-RBR; 2802 including 1596 males and 1206 females) were identified. Their data were compared with a control group of 7416 patients who ranged in age from 20 to 64 years old and were registered on the J-RBR over the same period. In addition, the clinical and pathological classifications of 276 very elderly patients were also analyzed. RESULTS: The indications for biopsy were nephrotic syndrome (NS) in 36.2 and 50.7 % of the elderly and the very elderly patients, chronic nephritic syndrome in 31.8 and 17.4 %, and acute kidney injury including rapidly progressive glomerulonephritis in 18.6 and 22.5 %, respectively. Primary glomerular disease was the most frequent diagnosis, followed by MPO-ANCA-positive nephritis, IgA nephropathy (IgAN), and diabetic nephropathy. In primary GN including IgAN, membranous nephropathy (MN) was the most frequent histological type, followed by IgAN and minor glomerular abnormalities. A comparison with the control group showed that MN, MPO-ANCA-positive nephritis, and amyloid nephropathy were more common in the elderly (P < 0.001), and IgAN was less common (P < 0.001). As for nephrotic syndrome in the elderly, MN was the most common histological type, followed by minimal change NS, diabetic nephropathy, amyloid nephropathy, and focal segmental glomerulosclerosis. There was a significant discrepancy between the urinary protein/creatinine ratio and daily proteinuria after the 7th decade of life. CONCLUSIONS: Renal biopsy is a valuable diagnostic tool, even in elderly and very elderly Japanese patients. In the future, modified clinical guidelines for elderly renal disease should be developed.Clinical and Experimental Nephrology 10/2012; DOI:10.1007/s10157-012-0673-8 · 1.71 Impact Factor
Article: Pre-Existing Arteriosclerotic Intimal Thickening in Living-Donor Kidneys Reflects Allograft Function[Show abstract] [Hide abstract]
ABSTRACT: Donor shortage is a serious problem worldwide and it is now debated whether kidneys from marginal donors are suitable for renal transplantation. Recent studies have shown that the findings of preimplantation kidney biopsy are useful to evaluate vasculopathy in the donated kidney, and may predict transplant outcomes in deceased- donor kidney transplantation. However, few studies have focused on the pathological findings of preimplantation biopsy in living-donor kidney transplantation. Therefore, we investigated whether arteriosclerotic vasculopathy in living-donor kidneys at the time of transplantation predicts the recipient's kidney function (allograft function) later in life. We retrospectively analyzed 75 consecutive adult living-donor kidney transplants performed at Kagawa University Hospital. Renal arteriosclerotic vasculopathy was defined according to the presence of fibrous intimal thickening in the interlobular artery. Forty-one kidneys exhibited mild arteriosclerotic vasculopathy on preimplantation kidney biopsies. The decreases in estimated glomerular filtration rate after donation were similar in donors with or without renal arteriosclerotic vasculopathy. Pre-existing arteriosclerotic vasculopathy did not affect graft survival rate, patient survival rate or the incidence of complications. Recipients of kidneys with arteriosclerotic vasculopathy had lower allograft function at 1 and 3 years after transplantation than the recipients of arteriosclerosis-free kidneys with or without donor hypertension. In multivariate analysis, fibrous intimal thickening on preimplantation biopsy was predictive of reduced allograft function at 1 year after transplantation. The present study demonstrated that mild arteriosclerotic vasculopathy in the donated kidney is an important pathological factor that reflects future impaired function of renal allografts from marginal donors.American Journal of Nephrology 07/2012; 36(2):127-35. DOI:10.1159/000340035 · 2.65 Impact Factor
Article: [Case report; A case of IgG4-related tubulointerstitial nephritis complicated nephrotic syndrome].Nihon Naika Gakkai Zasshi 03/2012; 101(3):759-62.
Article: Early treatment with olmesartan prevents juxtamedullary glomerular podocyte injury and the onset of microalbuminuria in type 2 diabetic rats.[Show abstract] [Hide abstract]
ABSTRACT: Studies were performed to determine if early treatment with an angiotensin II (Ang II) receptor blocker (ARB), olmesartan, prevents the onset of microalbuminuria by attenuating glomerular podocyte injury in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with type 2 diabetes mellitus. OLETF rats were treated with either a vehicle, olmesartan (10 mg/kg/day) or a combination of nonspecific vasodilators (hydralazine 15 mg/kg/day, hydrochlorothiazide 6 mg/kg/day, and reserpine 0.3 mg/kg/day; HHR) from the age of 7-25 weeks. OLETF rats were hypertensive and had microalbuminuria from 9 weeks of age. At 15 weeks, OLETF rats had higher Ang II levels in the kidney, larger glomerular desmin-staining areas (an index of podocyte injury), and lower gene expression of nephrin in juxtamedullary glomeruli, than nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. At 25 weeks, OLETF rats showed overt albuminuria, and higher levels of Ang II in the kidney and larger glomerular desmin-staining areas in superficial and juxtamedullary glomeruli compared to LETO rats. Reductions in mRNA levels of nephrin were also observed in superficial and juxtamedullary glomeruli. Although olmesartan did not affect glucose metabolism, it decreased blood pressure and prevented the renal changes in OLETF rats. HHR treatment also reduced blood pressure, but did not affect the renal parameters. This study demonstrated that podocyte injury occurs in juxtamedullary glomeruli prior to superficial glomeruli in type 2 diabetic rats with microalbuminuria. Early treatment with an ARB may prevent the onset of albuminuria through its protective effects on juxtamedullary glomerular podocytes.American Journal of Hypertension 02/2012; 25(5):604-11. DOI:10.1038/ajh.2012.1 · 3.67 Impact Factor
Article: 728 ULTRASOUND DOPPLER MEASUREMENT OF AORTIC BLOOD FLOW AND INTRARENAL VASCULAR RESISTANCE IN CHRONIC KIDNEY DISEASE[Show abstract] [Hide abstract]
ABSTRACT: Aim: Intrarenal vascular resistance estimated by resistive index (RI) is measured with renal duplex ultrasonography (RDU). Recently it has been reported that RI is useful to evaluate renal function of chronic kidney disease (CKD) and estimate prognosis of the kidney. As aortic blood flow is driving force of renal blood flow, they should be related each other. In the present study, we assessed relationships between aortic and intrarenal blood flow and CKD stages. Study Design: Cross-section study. Estimated GFR (mL/min/1.73m2) was calculated by modified MDRD formula by using serum creatinine level measured on closest day to each RDU date. We evaluated peak systolic velocity, end diastolic velocity and RI of sectional artery and interlobular artery, peak aortic velocity (PAV) and kidney size, which were compared with CKD stages. This study was permitted by medical ethics committee in Tohoku University. [Subject] CKD patients of 184 visiting our hypertension units in Tohoku university hospital during 2007 were examined in RDU. Patients with renovascular hypertension were excluded. [Results] Renal size from average longest diameter of each bilateral kidney was significantly correlated with CKD stages. Both RI on segmental and interlobular arteries were significantly correlated with CKD stages. PAV below the age of 40 is significantly faster than that above 40. PAV on CKD stage 1 is significantly faster than that on the other stages. Conclusion: RDU examination is available to evaluate renal remaining renal function. It notes that young patient tends to present higher PAV and higher intrarenal peak systolic velocity.Journal of Hypertension 01/2012; 30:e211. DOI:10.1097/01.hjh.0000420404.67000.81 · 4.22 Impact Factor
Article: Expression of vimentin and high-molecular-weight cytokeratin (clone 34ßE12) in differentiating reactive renal tubular cells from low-grade urothelial carcinoma cells in voided urine.[Show abstract] [Hide abstract]
ABSTRACT: Reactive renal tubular cells show features of an atypical repair reaction. Differentiation between reactive renal tubular cells and low-grade urothelial carcinoma (LG-UC) cells can therefore be a diagnostic challenge based on morphology alone. In this study, we evaluated the diagnostic utility of vimentin and a high-molecular-weight cytokeratin antibody (clone 34ßE12) in differentiating reactive renal tubular cells from LG-UC. We evaluated voided urine cytology and surgical specimens from 40 patients with renal disease, and 17 patients with LG-UC. All slides were stained with vimentin and 34ßE12. In the reactive renal tubular cells in voided urine cytology, vimentin showed strong cytoplasmic staining in 39/40 (97.5%) cases, but all were negative for 34ßE12. LG-UC cells showed positive staining for 34ßE12 in 3/17 (17.6%) cases, whereas none were positivity for vimentin. The reactive renal tubular cells of histological specimens in the renal disease group demonstrated positive for vimentin in all 40 cases and all were negative for 34ßE12. The LG-UC group showed abnormal staining for 34ßE12 in 4/17 (23.5%) cases, whereas none were positive for vimentin. Vimentin expression in urine cytology can help to distinguish reactive renal tubular cells from LG-UC. However, 34ßE12 does not appear to be a useful adjunct to distinguish these two groups in voided urine cytology.Cytopathology 08/2011; 22(4):247-52. DOI:10.1111/j.1365-2303.2010.00791.x · 1.47 Impact Factor
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ABSTRACT: Drug discovery and development is a lengthy and expensive process. Testing new agents in humans at an early stage could reduce the time and costs involved in identifying drugs that are likely to succeed in clinical studies. New guidance has outlined the concept of exploratory clinical trials, which provide important information on a drug's distribution as well as its physiological and pharmacological effects in humans. This strategy reduces the need for preclinical testing by limiting the dose and duration of exposure to a new drug in humans to below those required by the traditional testing of investigational new drugs. Exploratory, first-in-man studies should provide insights into human physiology and pharmacology, identify therapeutic targets relevant to disease and increase our knowledge of a drug's characteristics. Implementation of a new drug also requires the development of useful biomarkers of disease and of the drug's efficacy, as well as sensitive molecular imaging techniques. In this Review, we outline the benefits of exploratory clinical trials, especially in academia, and provide an overview of the experimental tools necessary for rational drug discovery and development.Nature Reviews Nephrology 07/2011; 7(8):469-77. DOI:10.1038/nrneph.2011.84 · 7.94 Impact Factor
Article: Angiotensin II shifts insulin signaling into vascular remodeling from glucose metabolism in vascular smooth muscle cells.[Show abstract] [Hide abstract]
ABSTRACT: To clarify the role of angiotensin II (Ang II) in insulin-induced arteriosclerosis, we examined the effects of Ang II on insulin-induced mitogen-activated protein (MAP) kinase activation and cellular hypertrophy in rat vascular smooth muscle cells (VSMCs). Phosphorylated MAP kinases were detected with western blot analysis. Cellular hypertrophy and glucose uptake were evaluated from incorporation of [(3)H]-labeled-leucine and -deoxy-D-glucose, respectively. Cell sizes were measured by Coulter counter. While Ang II (100 nmol/l, 18 h) augmented cellular hypertrophy by insulin (10 nmol/l, 24 h), insulin alone did not affect hypertrophy without Ang II pretreatment. Insulin increased p38MAP kinase and c-Jun N-terminal kinase (JNK) phosphorylation; in the presence of Ang II, p38MAP kinase, and JNK were further activated by insulin. Treatment of a p38MAP kinase inhibitor, SB203580 (10 µmol/l), and a JNK inhibitor, SP600125 (20 µmol/l), abrogated the [(3)H]-leucine incorporation by insulin in the presence of Ang II. Both the Ang II receptor blocker, RNH-6270 (100 nmol/l), and an antioxidant, ebselen (40 µmol/l), inhibited vascular cell hypertrophy. Specific depletion of insulin receptor substrate-1 with small interfering RNA increased [(3)H]-leucine incorporation by insulin (10 nmol/l, 24 h); pretreatment with Ang II attenuated insulin (10 nmol/l, 30 min)-induced glucose uptake. Ang II attenuates insulin-stimulated glucose uptake and enhances vascular cell hypertrophy via oxidative stress- and MAP kinase-mediated pathways in VSMCs. Ang II may also cause insulin signaling to diverge from glucose metabolism into vascular remodeling, affecting insulin-induced arteriosclerosis in hypertension.American Journal of Hypertension 06/2011; 24(10):1149-55. DOI:10.1038/ajh.2011.114 · 3.67 Impact Factor
Article: Relationship Between Urinary Angiotensinogen and Salt Sensitivity of Blood Pressure in Patients With IgA Nephropathy[Show abstract] [Hide abstract]
ABSTRACT: We demonstrated previously that the blood pressure of patients with IgA nephropathy becomes salt sensitive as renal damage progresses. We also showed that increased urinary angiotensinogen levels in such patients closely correlate with augmented renal tissue angiotensinogen gene expression and angiotensin II levels. Here, we investigated the relationship between urinary angiotensinogen and salt sensitivity of blood pressure in patients with IgA nephropathy. Forty-one patients with IgA nephropathy consumed an ordinary salt diet (12 g/d of NaCl) for 1 week and a low-salt diet (5 g/d of NaCl) for 1 week in random order. The salt-sensitivity index was calculated as the reciprocal of the slope of the pressure-natriuresis curve drawn by linking 2 data points obtained during consumption of each diet. The urinary angiotensinogen:creatinine ratio was significantly higher in patients who consumed the ordinary salt diet compared with the low-salt diet (17.5 μg/g [range: 7.3 to 35.6 μg/g] versus 7.9 μg/g [range: 3.1 to 14.2 μg/g] of creatinine, respectively; P<0.001). The sodium sensitivity index in our patients positively correlated with the glomerulosclerosis score (r=0.43; P=0.008) and changes in logarithmic urinary angiotensinogen:creatinine ratio (r=0.37; P=0.017) but not with changes in urinary protein excretion (r=0.18; P=0.49). In contrast, changes in sodium intake did not alter the urinary angiotensinogen:creatinine ratio in patients with Ménière disease and normal renal function (n=9). These data suggest that the inappropriate augmentation of intrarenal angiotensinogen induced by salt and associated renal damage contribute to the development of salt-sensitive hypertension in patients with IgA nephropathy.Hypertension 06/2011; 58(2):205-11. DOI:10.1161/HYPERTENSIONAHA.110.166843 · 7.63 Impact Factor
Article: Prorenin induces vascular smooth muscle cell proliferation and hypertrophy via epidermal growth factor receptor-mediated extracellular signal-regulated kinase and Akt activation pathway[Show abstract] [Hide abstract]
ABSTRACT: It is widely acknowledged that the (pro)renin receptor mediates angiotensin (Ang) II-dependent and Ang II-independent effects of prorenin. We examined the effect of prorenin on vascular smooth muscle cell (VSMC) signal transduction, proliferation, and hypertrophy. Recombinant rat prorenin dose-dependently increased extracellular signal-regulated kinase (ERK) 1/2 and Akt phosphorylation in rat VSMCs. Prorenin also significantly increased cell number, and [H]-thymidine and [H]-leucine incorporation, which were attenuated by pretreatment with inhibitors for ERK kinase and phosphatidylinositol 3 kinase. Prorenin was also found to stimulate epidermal growth factor (EGF) receptor and Src phosphorylation. Pretreatment of VSMCs with an EGF receptor tyrosine kinase inhibitor and a Src inhibitor significantly attenuated the prorenin-induced increase in ERK 1/2 and Akt phosphorylation, as well as DNA and protein synthesis. Prorenin-induced phosphorylation of the EGF receptor, ERK 1/2, and Akt, as well as DNA and protein synthesis were all blocked by (pro)renin receptor siRNA, but not by an Ang II type 1 receptor blocker, candesartan, nor an Ang-converting enzyme inhibitor, captopril. These results reveal that prorenin directly stimulates VSMC proliferative and hypertrophic changes, dependent on the (pro)renin receptor, independent of Ang II. Furthermore, EGF receptor-mediated ERK 1/2 and Akt activation contributes to prorenin-dependent proliferative and hypertrophic effects in VSMCs.Journal of Hypertension 04/2011; 29(4):696-705. DOI:10.1097/HJH.0b013e328343c62b · 4.22 Impact Factor
Article: Japan Renal Biopsy Registry: the first nationwide, web-based, and prospective registry system of renal biopsies in Japan[Show abstract] [Hide abstract]
ABSTRACT: The Committee for the Standardization of Renal Pathological Diagnosis and the Working Group for Renal Biopsy Database of the Japanese Society of Nephrology started the first nationwide, web-based, and prospective registry system, the Japan Renal Biopsy Registry (J-RBR), to record the pathological, clinical, and laboratory data of renal biopsies in 2007. The patient data including age, gender, laboratory data, and clinical and pathological diagnoses were recorded on the web page of the J-RBR, which utilizes the system of the Internet Data and Information Center for Medical Research in the University Hospital Medical Information Network. We analyzed the clinical and pathological diagnoses registered on the J-RBR in 2007 and 2008. Data were collected from 818 patients from 18 centers in 2007 and 1582 patients from 23 centers in 2008, including the affiliated hospitals. Renal biopsies were obtained from 726 native kidneys (88.8%) and 92 renal grafts (11.2%) in 2007, and 1400 native kidneys (88.5%) and 182 renal grafts (11.5%) in 2008. The most common clinical diagnosis was chronic nephritic syndrome (47.4%), followed by nephrotic syndrome (16.8%) and renal transplantation (11.2%) in 2007. A similar frequency of the clinical diagnoses was recognized in 2008. Of the native kidneys, the most frequent pathological diagnosis as classified by pathogenesis was immunoglobulin (Ig) A nephropathy (IgAN) both in 2007 (32.9%) and 2008 (30.2%). Among the primary glomerular diseases (except IgAN), membranous nephropathy (MN) was the most common disease both in 2007 (31.4%) and 2008 (25.7%). In a cross-sectional study, the J-RBR has shown IgAN to be the most common disease in renal biopsies in 2007 and 2008, consistent with previous Japanese studies. MN predominated in the primary glomerular diseases (except for IgAN). The frequency of the disease and the clinical and demographic correlations should be investigated in further analyses by the J-RBR.Clinical and Experimental Nephrology 03/2011; 15(4):493-503. DOI:10.1007/s10157-011-0430-4 · 1.71 Impact Factor
Article: Effects of mineralocorticoid receptor blockade on glucocorticoid-induced renal injury in adrenalectomized rats[Show abstract] [Hide abstract]
ABSTRACT: Aldosterone is well recognized as the selective physiological ligand for mineralocorticoid receptor in epithelia. However, in-vitro studies have demonstrated that the affinity of aldosterone and glucocorticoids for mineralocorticoid receptor is similar. We hypothesized that glucocorticoids are involved in the development of renal injury through an mineralocorticoid receptor-dependent mechanism. Uninephrectomized (UNX) rats were treated with 1% NaCl and divided into three groups: vehicle, bilateral adrenalectomy (ADX) + hydrocortisone (HYDRO; 5 mg/kg/day, s.c.), ADX + HYDRO + eplerenone (0.125% in chow). HYDRO-treated UNX-ADX rats showed increased blood pressure and urinary albumin-to-creatinine ratio with an increase in the expression of the mineralocorticoid receptor target genes, serum and glucocorticoid-regulated kinases-1 and Na+/H+ exchanger isoform-1, in renal tissues. HYDRO treatment induced morphological changes in the kidney, including glomerulosclerosis and podocyte injury. Treatment with eplerenone markedly decreased the gene expression and reduced the albuminuria and renal morphological changes. In contrast, dexamethasone (0.2 mg/kg per day, s.c.) + UNX + ADX induced hypertension and albuminuria in different groups of rats. Eplerenone failed to ameliorate these changes. Our findings indicate that chronic glucocorticoid excess could activate mineralocorticoid receptor and, in turn, induce the development of renal injury.Journal of Hypertension 02/2011; 29(2):290-8. DOI:10.1097/HJH.0b013e32834103a9 · 4.22 Impact Factor
Nippon Jinzo Gakkai shi 01/2011; 53(8):1074-138.
Top Journals
Tohoku University
Miyagi, Japan
- Tohoku Medical Megabank Organization
Kagawa University
- • Department of Cardiorenal and Cerebrovascular Medicine
- • Faculty of Medicine
- • Department of Pharmacology
- • School of Medicine
Beverly Hospital, Boston MABeverly, Massachusetts, United States
Tulane UniversityNew Orleans, Louisiana, United States
Kawasaki Medical UniversityKurasiki, Okayama, Japan
Osaka City UniversityŌsaka, Ōsaka, Japan
The University of Tokushima
Tokusima, Tokushima, Japan
- Department of Pharmacology
Osaka University
Ōsaka-shi, Osaka-fu, Japan
- Department of Internal Medicine


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The Jewish Education Initiative held its largest event of the year, the Freedom Seder, last Sunday in accordance with Passover. ...
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Jake Rubin, Executive Director Originally from Richmond, Jake holds a B.A. in Religious Studies from the University. In 2009, he received his Rabbinic ordination from the Reconstructionist Rabbinical College (RRC), from which he also graduated with a Master's of Arts in Hebrew Letters. While a student at RRC, Jake served as the Jewish Student Advisor at Swarthmore College, an affiliate of Hillel of Greater Philadelphia. He also worked as a chaplain for Jewish Family and Children's Service of Greater Philadelphia and as an educator and student Rabbi for a number of congregations during his time at RRC. Prior to rabbinical school, Jake was a fellow for PANIM: The Institute for Jewish Leadership and Values. Jake has joined our community along with his wife Lindsay and their children Sophie and Jonah. He can be reached at email@example.com.
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Born and raised in Fairfield, Connecticut, Debbie began her undergraduate studies at the University of Colorado in Boulder, and earned her degree at Fairfield University graduating cum laude with B.A. in History and a minor in Religious Studies. Post college, she worked in finance at a Hedge Fund, in Greenwich, Connecticut. Debbie then changed her career path to follow her passion for education. She earned a graduate degree in Secondary History Education with a Master of Arts in Teaching. To continue on the path of education, in 2013-2014, Debbie moved to Israel where she volunteered and taught English to underprivileged students in Netanya for MASA Israel Teaching Fellows. While in Israel, Debbie was selected to take part in the MASA-Hillel Fellowship, which led her to join our team at the Brody Jewish Center, Hillel at UVa. In her spare time, you can find Debbie staying active by traveling, cycling, running or skiing. She can be reached email@example.com.
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text:
Announcers in the championship.....
First of all....
If LoL is going to be a global eSports powerhouse... they should hire competent announcers.
Its ABF vs M5 not AZF vs TSM.
Its AZF in the tourney not AZB chicky..
Phreak and remmy are fine.. other 2 not so much
sorry for the repost ... kept giving me an error message
Actually it is AZF vs TSM.
low elos always think they are right and confident when they're DEAD WRONG LOOL! tsm vs frost buddy they said it a million times.. but i do agree on the commentators being very boring i switched to the korean version at least theyre fun to listen to instead of talking about details about the game all game..
|All times are GMT -8. The time now is 10:29 AM.
(c) 2008 Riot Games Inc


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Urbangreen Furniture Urban Basics Twin 3 Drawer Storage Platform Bed
Urbangreen Furniture Urban Basics Twin 3 Drawer Storage Platform Bed
Weights & Dimensions
|Bed Type: Platform
|Finish: 1: Beige
|Finish: 2: Black
|Finish: 3: Blue
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|Finish: 5: Cherry
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|Finish: 7: Green
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|Finish: 10: Orange
|Finish: 11: Pink
|Finish: 12: Red
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|Finish: 14: Walnut
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|Finish: 16: Yellow
|Distressed: No
|Frame Material: Wood
|Bed Size: Twin
|Gender: Unisex
|Underbed Storage: Yes
|Hidden Storage: Yes
|Eco-Friendly: Yes
|Country of Manufacture: United States
Still have questions about this product? We're here to help
Urbangreen Furniture Urban Basics Twin 3 Drawer Storage Platform Bed
About the ManufacturerUrbangreen Furniture is a company of home furnishings professionals based in Brooklyn, USA. A team with over 70 years of combined experience; they locally design and handcraft real wood furniture - directly available to you online and in-store.
|5 star
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Beautiful bad - not accurate swatch color
gal from BROOKLYN, NY– Verified Buyer
The bed is really beautiful!
OUR SKU # UBGR1061Urban Basics Twin 3 Drawer Storage Platform Bed is also sometimes listed under the following manufacturer numbers: UB1TCAT, UB1TCCL, UB1TCTO, UB1TCUN, UB1TMAM, UB1TMBK, UB1TMBL, UB1TMCL, UB1TMDFBK, UB1TMDFBL, UB1TMDFFC, UB1TMDFGR, UB1TMDFGY, UB1TMDFOR, UB1TMDFRD, UB1TMDFTUR, UB1TMDFWH, UB1TMDFYE, UB1TMEB, UB1TMES, UB1TMFC, UB1TMGR, UB1TMPK, UB1TMRD, UB1TMSL, UB1TMTO, UB1TMUN, UB1TMWS, UB1TMWT, UB1TMYE, UB1TWBD, UB1TWCL, UB1TWTO, UB1TWUN


text:
Luxury property in Resort
from £41 /night help
Estimated nightly price based on a weekly stay. Excludes fees (if applicable). Enter your dates to see the total cost.
Availability Your dates are available
Apartment | 2 bedrooms | sleeps 6
|Key Info
This stunning apartment is brand new and is located in the Mar Menor Golf Resort, with stunning views of the golf course. The apartment is beautifully decorated and has everything you could need for a perfect relaxing holiday. There are 2 bedrooms and 2 bathrooms and a very bright, good sized balcony. This apartment is ideal for both families and small groups of golfers looking for a self catering holiday.
The lounge area has a comfortable sofa, flatscreen TV, DVD and satellite TV. The lounge has large patio doors that lead to the balcony that overlooks the pool and golf course. The local towns are on very short distance as well as the famous sandy beaches.
N.B. Photos are for display purposes only. Please contact owner for more information.
|Sleeps up to 6, 2 bedrooms
|Will consider
|Corporate bookings, Long term lets (over 1 month)
|Family friendly
|Great for children of all ages, Suitable for people with restricted mobility
|No pets allowed, No smoking at this property
Features and Facilities
|Internet access, DVD player
|Shared outdoor pool (unheated), Children's pool
|Air conditioning, TV, Safe, Satellite TV, Wi-Fi available
|Kettle, Toaster
|Cooker, Microwave, Fridge, Freezer, Washing machine
|2 bedrooms, 2 bathrooms of which 1 Family bathrooms and 1 En suites
|1 Sofa beds, Single beds (4), Dining seats for 4
|Linen provided, Towels provided
|Shared outdoor pool (unheated), Balcony or terrace, Shared garden
|Secure parking
About this location
The Murcia region
Mar Menor Golf Resort
About the owner
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26 Aug 2013
"Excellent value family apartment on 5* resort."
From our initial enquiry,the service we received from Bianca the owner & Jac the property manager was first class. Nothing was too much trouble,& Jac was keen to provide us with local information & al… More
Thank you very much for your lovely review! It was very nice to have you and your family as our guest and hope we can welcome you again in the future! We have more apartments in the same block, so if you want to come with more people we always have availability.
Thanks again and see you soon!
This advert is created and maintained by the advertiser; we can only publish adverts in good faith as we don't own, manage or inspect any of the properties. We advise you to familiarise yourself with our terms of use.
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The keeper of Lost Causes (Department Q 1) (original 2007; edition 2011)
by Jussi Adler-Olsen, Lisa Hartford
Work details
The Keeper of Lost Causes by Jussi Adler-Olsen (2007)
Books Read in 2014 (197)
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Nordic Crime Fiction (37)
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Hooray for a new Scandinavian detective series! This one is set in Denmark, allegedly the happiest country in the world after Bhutan, but it's still pretty dark. The book cover is a blatant ripoff of Girl With The Dragon Tattoo, but the main character here is a sexist and difficult detective who is in recovery from a shooting where one of his partners was killed and one paralyzed. Carl Morck holds himself responsible for the killer's escape. Because he's impossible to work with but effective, he gets banished to the basement and to a new Department Q for cold cases that remain politically hot. His admin Assad is a man of mystery who proves to have skills beyond cooking spicy MidEastern food and cleaning. Their first case is that of a politician, Merete Lynggaard, who has been missing for almost five years and who also has a dreadful life altering event in her background. The suspense level starts low and ratchets up steadily, building to a most satisfying outcome and to the next in the Department Q series. I can't wait!
This is the first in a series of "Department Q" Danish police procedurals. Carl Mørck, is a deputy detective superintendent who been is relegated to the basement in an office where it is deemed he'll be no trouble. And at first he wants nothing more than to put his feet up and do nothing. When he learns the department was getting a windfall by creating this department of "lost causes" he uses that knowledge to his advantage to get an assistant and nice digs. Carl has a history of his own. He was involved in a shootout that killed one of his partners and paralyzed the other.
Assad, his assistant, a Muslim and another cast-off, seems to be always one step ahead. He's a delightful character. They are tasked with investigating the disappearance, ostensibly a drowning, of a prominent political leader. This was the part I found totally implausible: a woman kept in a chamber for five years in which the atmospheric pressure is being gradually increased. She is fed through an airlock and tries to retain her sanity. The story that gradually unfolds concerns an intricate plot to get revenge for something that had happened years before..
It took me a while to get into this book, and I must say it was only the quirkiness of the main characters that kept me going. Perhaps it was the structure I found annoying, but the book became more intriguing as it progressed. I'll try another in the series, but we'll just have to see.
Note: AKA The Keeper of Lost Causes.
In 2002, Merete Lynggaard, a prominent Danish politician, went missing on a car ferry from Denmark to Germany. She left behind her younger brother, Uffie, who had not spoken for 15 years, since an automobile accident they were involved in took their parents' lives. Merete hasn't been heard from since and it is presumed she went overboard and drowned.
In 2007, unpopular Police Detective Carl Morck was involved in a shooting in which one of his partners died and the other is in critical condition, probably paralyzed for life. Upon his return from medical leave, his boss Marcus Jacobsen couldn't figure out what to do with him. Luckily, Parliament granted the police department an appropriation to create a department to re-examine cold cases, Department Q. Locate it in the basement which would minimize the risk of Morck interacting with other policemen and it would be a perfect place for Morck who can be abrasive at times.
Forced to chose a case to work on, Morck and his Syrian assistant Hafez al-Assad, unintentionally pick the Lynggaard disappearance–high profile and never solved. Morck initially shows no interest in the case but as Assad uncovers interesting information, Morck begins a real investigation.
Of course the officer who handled the initial call was the bumbling Bak. And, of course, Morck and Assad find many avenues of inquiry never pursued during the initial investigation.
Adler-Olsen has created a good detective in Morck and his comical sidekick Assad. Morck is the Danish version of the chain smoking brooding cop we've all come to know and love in American crime fiction. He's estranged from his wife who lives in a cottage next door. His stepson lives upstairs and sponges off Morck and he's got a finicky tenant who lives in the basement.
The Keeper of Lost Causes has an interesting premise which I won't tell you about since it will spoil the fun. Adler-Olsen does go back and forth between 2002 and 2007 but that merely enhances the plot. Readers will be guessing until almost the end about 'who done it'.
Although I enjoyed The Keeper of Lost Causes and would read the next book in this 5 book series, I did find it a slower read than most mysteries, even the other Nordic translations I've read. Possibly a little tighter editing might have helped, but all in all, it's a good series.
I read this book as a way of dipping my toes into Nordic Noir. I enjoyed the main character, and especially his sidekick, Assam. But the description of what was happening to the kidnapped victim were really dark for me. It will be interesting to follow what happens with Dept Q in the future.
This is the first book in Jussi Alder-Olsen's Q-series concerning Danish police detective Carl Morck. I have to admit, I always liked reading Scandinavian detectives a lot. But after years of reading them, I grew a bit tired. Had they first been very new and not as cliché as most US/UK detectives, I got very used to the Scandinavian theme as well.
But this book was different, I really enjoyed it. It was an easy read, but very nice and with a lot of suspense in it.
I've ever since reading this book planned to read the rest of this series, but so far, I've only read the second book.
References to this work on external resources.
Wikipedia in English (1)
No descriptions found.
Chief detective Carl M?ck, recovering from what he thought was a career-destroying gunshot wound, is relegated to cold cases and becomes immersed in the five-year disappearance of a politician.
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Joe Christensen covered Major League Baseball for 15 years, including three seasons at the Baltimore Sun and eight at the Star Tribune, before switching to the college football beat. He's a Faribault, Minn., native who graduated from the University of Minnesota in 1996. He covered Jim Wacker's Gophers for the Minnesota Daily and also wrote about USC, UCLA and the Rose Bowl for the Riverside Press-Enterprise before getting this chance to cover football again.
Email Joe to talk about the Gophers.
EAST LANSING, Mich. -- Da'Jon McKnight has had a breakout day for the Gophers, and it's only halftime. But Minnesota is going to need even more offense if it's going to win for the second straight week.
The senior receiver has piled up 121 yards and two touchdowns, and Jordan Wettstein's 27-yard field goal gave the Gophers a lead shortly before halftime. But the 15th-ranked Spartans responded by going 74 yards in 51 seconds, and fullback Todd Anderson's first career TD reception with five seconds remaining sent Minnesota into the locker room trailing 21-17.
McKnight caught a 10-yard pass from MarQueis Gray on the Gophers' first drive, broke a couple of tackles and turned the play into Minnesota's longest from scrimmage this season, a 64-yard romp into the end zone. It was the first time in conference play that Minnesota has scored first.
The Gophers got a break later in the quarter when Spartan tailback Edwin Baker fumbled, and linebacker Keanon Cooper fell on the ball on Michigan State's 26. After a 13-yard scramble by Gray rolled up half the necessary yardage, McKnight made a difficult catch in the left corner of the end zone, going up and over cornerback Johnny Adams, then coming down with his feet in bounds.
Michigan State is outgaining the Gophers, 281 yard to 216 after two quarters, most of it coming through the air. Spartans quarterback Kirk Cousins has thrown for 223 yards, while Gray has 163 for the Gophers.
McKnight is only 25 yards from his career high of 146, set against New Mexico State in September.
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Launcher Update
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Sorry CM wiz, Archon wizard only. :P
So yeah, rate the wizard that is an Archon above your next post.
#1) What you think their top 3 best item is
#2) Any nice comments
#3) Any suggestions/improvements
#4) ???
#5) Profit
edit: make sure you're profile isn't standing in buffs
Edited by metaStatic#6741 on 5/27/2013 12:39 AM PDT
Posts: 3,943View profile
1) That ammy would be so good if it had been an Int roll instead of vit. It's still pretty good though. Too bad LoH Is so bad for Archon. WH is super high dps, and the gloves are pretty nice. It's so hard to craft decent gloves, as I'm finding.
2) You can probably use some extra armor and/or resists to let you run higher MP when you raise your dps a bit. You can probably also swap the vit gems in pants for Int if you're not pushing MP too high (like MP6 or lower). You could also try getting a more useful SoJ, if there's a spectral blades one, but I can't remember to be honest. I've never looked for SB stuff.
3) Try FN over Blizzard for time outside of Archon. It's pretty good CC if you can refresh it fast enough.
My profile is just self buffs with Scoundrel if that matters.
Generalhan #3180
Posts: 156View profile
And i'll kick off the rating
1) Top three items
Crafted Bracers
2) Nice comments
Well balanced archon
Skill build looks pretty fun to play :D
3) Suggestions/Improvements
Armour and all resists could be worked on a little - keep crafting bracers and see if you can land one with similar stats AND all resist. Also the Zuni boots could grab some AR too at some stage
Don't know the numbers but if you switched your amethyst in the pants to the helm does that give you higher vitality?
How do you fare against reflect damage with just blood magic? Maybe consider a LS sword and switch blood magic rune to MOAR damage
Overall - 7.5/10
EDIT: Still new to rating other archons - please be nice :D
Edited by Generalhan#3180 on 5/27/2013 1:06 AM PDT
Posts: 6View profile
1. Your gear is so much better than mine. (I'm poor). Nice sword. Nice amulet. Nice rings. Nice bracers too.
2. I feel like I've seen swords with more DPS that still have the socket/CD/LS/Int. When you find an upgrade you should let me "borrow" your old one. :)
I could use some constructive criticism. My budget is only 30 mil. Should I save up for a better weapon?
Edited by Josephus#1444 on 5/27/2013 1:14 AM PDT
Posts: 5View profile
Don't think im qualified enough to rate anybody's lol, but i really like mine to be rated. Like to know how am i doing so far with the pieces i've put together for a bit less than 15m (well excluding the sword, which i have to give my thanks to generalhan :D) and what should i be working on now.
Posts: 63View profile
1) Top three items
Mempo of Twilight
Zunimassa's Pox
2) Nice comments
I'm guessing you're not into perma-archon with the frost nova and lack of galvanizing wards.
3) Suggestions/Improvements
Since you have a black weapon, time to grab a badass Trim and boost that dps! Not sure what runs you normally do, could check out Maximus or Immortal Build for Enchantress.
4) Jellin ?
Yup I need to upgrade my helm.
5) Profit
Not enough mineral
1) Top three items
The Witching Hour
Echoing Fury
Gloves ?
2) Nice comments
Hail brother Archon, good luck on building yours!
3) Suggestions/Improvements
I think you should focus on your armors and jewelries at the moment. Get the extra 12% movement from either a Lacuni or Inna's Pants (Suggest Inna's Pants since you can craft some sick bracer now). Need not worry about the health loss losing your pants, the two extra socket could add amethyst (or topaz once your other gears are more stable yet still gaining dps). Replace Zunimassa's Marrow with a Tal Rasha 9% you'll get a exponential boost. I see you use Prismatic Armor, not a good trade off with Glass Cannon. Could switch to Shocking Aspect for more DPS or Pinpoint for Armor and Crit, or use another passive. Yours rings are good for now, I think you'll need the all res, but you should try getting to that after you upgraded your other pieces. Hope I was of help.
4) Jellin ?
Still need to upgrade my helm.
5) Profit
Not enough mineral
Take a shot. Looking at other peoples builds in these threads is how I got where I am
might stick to my rules :P
1) Weapon is pretty good. Did you craft it or buy? That Zuni chest is solid and that witching hour o_0
2) overall quite nice
3) it looks like you're stacking strength but dexterity is a better defensive stat. 500 dex = 20% dodge which is a massive eHP boost. also get a unity ring with high min-max damage and the same for your Zuni ring. anything that adds min-max damage is massive when you have a 666 triumvarat 8% zunis and a 6% Tal's ammy
I only have blood magic because I have no life regen anymore (andariel's and vile wards where my only source) and I drop archon for healing blades against reflect mobs. If I had a similar life steal weapon I would run living lightning for my CM refresh and MOAR power magic weapon rune ;)
Posts: 2,737View profile
@ regent
You use a Andy so 10/10 :D
A good unity will out dps your rare ring.
Other then that looking good.
im on my phone so cant see your stats on all your gear
Edited by YORI#1558 on 5/27/2013 2:33 AM PDT
HardDragon #2507
Posts: 8View profile
16k hp rly????????
Posts: 38View profile
Everyones gear is awesome... I just started wiz and love archon. I just dropped some gold on this guy, how am I doing so far?
redman,, you're on a good start. tal helm and 3 zuni piece, you're ehp archon with decent dps. yes going for above and beyond will need more gold but you're on a right track :D
although your hp could use a bit more
also, don't use shocking aspect for archon, it procs it badly. if you want, go with thunderstorm or energy armor/pinpoint :D
Posts: 754View profile
So i get to rate pich :D
What more can I say .. superb set with a great personality to go with it! 10/10!
P.S: craft that GG bracers & shoulders will you? :P
you know i still am trying to no avail. a lot of high dps ones but no all resist or vit so no go there.
do not rate me next poster. rate xfactor ty
Posts: 3,393View profile
@XFactor Your Wizard is my reference of how to gear up and improve my Archon Wizard. Thanks for the great advice you gave me on your thread :)
Posts: 234View profile
1) nice EF and Zuni pox!
2) Really nice Wiz overall, damage is great.
3) uhh not really qualified to advise on improvements, nothing stands out that wouldnt cost a lot of gold.
Posts: 1,823View profile
1) Nice Zuni pox and Tal Rasha Ammy.
2) Need a little more life
3) I think your Inna pants can be improved. Maybe instead of int/vit, get a 180+ vit version.
Posts: 458View profile
1) Awesome Mempo, Pox and WH.
2) Excellent wizard. Can only get better.
3)Try to aim for 45-50k HP with 85% mit and above unbuffed. Craft shoulders (high end and correct stat rolls beats VW anyday) and bracers (try to get armor roll instead of lightning resist). The rest of the items will be upgraded I'm sure.
Posts: 299View profile
@ Celanian
1) great rings
2) great looking wiz
3) living lightning can bring up achron much faster than forked lighting.
- Diablo III
Posts: 10,081View profile
1) Digging the shoulders. Nice mini-Vile Ward with the higher int, though less armor.
2) You're on the right path.
3) Definitely invest in a better weapon because all your stats essentially pump DPS based on your weapon. Once you get a real sweet one, then focus on maximizing each individual gear piece bit by bit.
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text:
Co-op Puzzler Tiny Brains Now On PlayStation 4
Publisher 505 Games has announced that Spearhead Games' highly-anticipated co-op indie puzzler Tiny Brains is now available for download in North America on the PlayStation® Network for PlayStation®4 for $19.99. The game will soon be available for PlayStation®4 in European territories and on Steam for Windows PC and PlayStation®3 for all territories this winter. Read the rest of this entry »
posted in Everyone 10+, National News, New Releases, Puzzle By: Tami | Print This Post


text:
Is Going To an Elite College Worth the Cost? 391
from the drag-out-the-causation-correlator dept.
We've improved Slashdot's video section; now you can view our video interviews, product close-ups and site visits with all the usual Slashdot options to comment, share, etc. No more walled garden! It's a work in progress -- we hope you'll check it out (Learn more about the recent updates).
It is, however, entirely suited to making bad jokes on
Q: What's yellow and sour and equivalent to the axiom of choice?
A: Zorn's Lemon!
The Caps Lock key is an arcane relic of the ancient IBM keyboards
Keyboards? Try ancient IBM typewriters.
And we needed it. In Conclusion, get off my lawn, whippersnapper.
CCI Power 6/40: one board, a megabyte of cache, and an attitude...