Strength Investigation of Thick Welded T-Joint using Finite Element Modelling

The paper discusses the computation of finite element modelling (FEM) of a thick welded joint as a high load transfer joint. The FEM utilises MSC PATRAN/NASTRAN software programs to predict and simulate the critical area of a welded joint. The elasticity limit for the specimen was determined and stress distribution was achieved in the joint to indicate critical parts of a welded T-joint and predict the critical locations for crack initiation in this kind of joint. Simulation and experimental results show good in agreement and the sources of some differences in these results are discussed.Defence Science Journal, 2010, 60(1), pp.112-118, DOI:http://dx.doi.org/10.14429/dsj.60.11

Strength investigation of thick welded T-Joint using finite element modelling

The paper discusses the computation of finite element modelling (FEM) of a thick welded joint as a high load transfer joint. The FEM utilises MSC PATRAN/NASTRAN software programs to predict and simulate the critical area of a welded joint. The elasticity limit for the specimen was determined and stress distribution was achieved in the joint to indicate critical parts of a welded T-joint and predict the critical locations for crack initiation in this kind of joint. Simulation and experimental results show good in agreement and the sources of some differences in these results are discussed

Acute-on-chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality

Existing chronic kidney disease (CKD) is among the most potent predictors of postoperative acute kidney injury (AKI). Here we quantified this risk in a multicenter, observational study of 9425 patients who survived to hospital discharge after major surgery. CKD was defined as a baseline estimated glomerular filtration rate <45ml/min per 1.73m2. AKI was stratified according to the maximum simplified RIFLE classification at hospitalization and unresolved AKI defined as a persistent increase in serum creatinine of more than half above the baseline or the need for dialysis at discharge. A Cox proportional hazard model showed that patients with AKI-on-CKD during hospitalization had significantly worse long-term survival over a median follow-up of 4.8 years (hazard ratio, 3.3) than patients with AKI but without CKD. The incidence of long-term dialysis was 22.4 and 0.17 per 100 person-years among patients with and without existing CKD, respectively. The adjusted hazard ratio for long-term dialysis in patients with AKI-on-CKD was 19.8 compared to patients who developed AKI without existing CKD. Furthermore, AKI-on-CKD but without kidney recovery at discharge had a worse outcome (hazard ratios of 4.6 and 213, respectively) for mortality and long-term dialysis as compared to patients without CKD or AKI. Thus, in a large cohort of postoperative patients who developed AKI, those with existing CKD were at higher risk for long-term mortality and dialysis after hospital discharge than those without. These outcomes were significantly worse in those with unresolved AKI at discharge

The Renoprotective Potential of Pentoxifylline in Chronic Kidney Disease

Current interventions with proven efficacy, such as glycemic and blood pressure control, dietary protein restriction, and angiotensin II blockade, slow the progression of chronic kidney disease (CKD); however, whether long-term cessation of CKD progression is possible remains unclear. Because of the pathogenetic complexity of this condition, multidrug interventions with the least adverse effects should be investigated as the next step in attempts to stop CKD progression. Pentoxifylline, a non-selective phosphodiesterase inhibitor with indiscernible toxicity, exerts potent inhibitory effects against cell proliferation, inflammation, and extracellular matrix accumulation, all of which play important roles in CKD progression. Pentoxifylline monotherapy markedly reduces proteinuria in patients with membranous nephropathy. Moreover, limited human studies have proven pentoxifylline efficacy in reducing proteinuria in patients with diabetes receiving angiotensin-converting enzyme inhibitors, and in patients with nephrotic syndrome secondary to lupus nephritis despite immunosuppressive therapy. Further clinical trials are necessary to examine whether pentoxifylline can improve renal outcomes in patients receiving interventions of proven efficacy

Cysteine-Rich Protein 61 Plays a Proinflammatory Role in Obstructive Kidney Fibrosis

<div><p>Cysteine-rich protein 61 (Cyr61) is a secreted matrix-associated protein that regulates a broad spectrum of biological and cellular activities. This study aimed to investigate the role of Cyr61 in progressive kidney fibrosis induced by unilateral ureteral obstruction (UUO) surgery in mice. The expression of Cyr61 transcripts and proteins in the obstructed kidneys were increased from day 1 and remained high until day 10 after surgery. Immunohistochemistry indicated that Cyr61 was expressed mainly in renal tubular epithelial cells. The upregulated Cyr61 in UUO kidneys was reduced in mice treated with pan-transforming growth factor-β (TGF-β) antibody. The role of TGF-β in tubular Cyr61 upregulation after obstructive kidney injury was further supported by experiments showing that TGF-β1 stimulated Cyr61 expression in cultured tubular epithelial cells. Notably, the upregulation of Cyr61 in UUO kidneys was followed by a marked increase in monocyte chemoattractant protein 1 (<em>MCP-1</em>) transcripts and macrophage infiltration, which were attenuated in mice treated with anti-Cyr61 antibodies. This proinflammatory property of Cyr61 in inducing <em>MCP-1</em> expression was further confirmed in tubular epithelial cells cultured with Cyr61 protein. The anti-Cyr61 antibody in UUO mice also reduced the levels of collagen type 1-α1 transcripts, collagen fibril accumulation evaluated by picrosirius red staining, and the levels of α-smooth muscle actin (<em>α-SMA</em>) transcripts and proteins on day 4 after surgery; however, the antifibrotic effect was not sustained. In conclusion, the TGF-β-mediated increase in tubular Cyr61 expression involved renal inflammatory cell infiltration through MCP-1 induction during obstructive kidney injury. The Cyr61 blockade attenuated kidney fibrosis in the early phase, but the antifibrotic effect could not be sustained.</p> </div

Primer sequences used for quantitative-PCR.

<p>Primer sequences used for quantitative-PCR.</p

Transforming growth factor-β (TGF-β) activity is associated with <i>Cyr61</i> gene expression after UUO.

<p>(<b>A</b>) Expression of <i>TGF-β1</i> transcripts normalized to 18S in the UUO kidneys, measured by Q-PCR. N = 8/time point. (<b>B–C</b>) Active (B) and total (C) TGF-β1 protein concentrations as determined by immunoassay in kidneys of mice receiving sham operation or UUO surgery. N = 4/time point. (<b>D</b>) Representative Western blot of Smad2/3 proteins in the UUO kidneys. (<b>E</b>) The graph summarizes the analysis for renal phosphorylated Smad2/3 normalized to total Smad2/3 after UUO. N = 4/time point. (<b>F</b>) The mice received an intraperitoneal injection of 10 µg/g BW pan-TGF-β monoclonal antibody (1D11) or control antibody (13C4) 2 hours before the UUO surgery and were euthanized the next day. Q-PCR showed that the increased <i>Cyr61</i> transcripts in the UUO kidneys were attenuated by 1D11 treatment. N = 4/group. The values are the mean+SD. *P<0.05 vs. sham operation kidneys; #P<0.05 vs. 1D11 treated.</p

Renoprotective effect of combining pentoxifylline with angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker in advanced chronic kidney disease

Several studies have shown the renoprotective effects of pentoxifylline in the treatment of chronic kidney disease (CKD). This study was conducted to examine whether there was an increased benefit of including pentoxifylline with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in the treatment of CKD. Methods: A single-center retrospective analysis was conducted. A total of 661 Stage 3B-5 CKD patients who received ACEI or ARB treatment were recruited. The patients were divided into the pentoxifylline use group and the no pentoxifylline group. Renal survival analysis of the two groups was compared. Subgroup analysis was performed by dividing the patients into lower [urine protein to creatinine ratio (UPCR)<1 g/g] and higher (UPCR≥1 g/g) proteinuria subgroups. Results: There was no between-groups difference regarding mortality and cardiovascular events. Addition of pentoxifylline showed a better renal outcome (p = 0.03). The protective effect of add-on pentoxifylline was demonstrated in the higher proteinuria subgroup (p = 0.005). In the multivariate Cox regression model, pentoxifylline use also showed a better renal outcome [hazard ratio (HR): 0.705; 95% confidence interval (CI): 0.498–0.997; p = 0.048]. This effect was more prominent in the higher proteinuria subgroup (HR: 0.602; 95% CI: 0.413–0.877; p = 0.008). Conclusion: In the advanced stages of CKD, patients treated with a combination of pentoxifylline and ACEI or ARB had a better renal outcome than those treated with ACEI or ARB alone. This effect was more prominent in the higher proteinuria subgroup. More large randomized control trials are needed to provide concrete evidence of the add-on effect of pentoxifylline