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Find video protocols related to scientific articles indexed in Pubmed.
Dynamic O-Linked N-Acetylglucosamine Modification of Proteins Affects Stress Responses and Survival of Mesothelial Cells Exposed to Peritoneal Dialysis Fluids.
J. Am. Soc. Nephrol.
PUBLISHED: 05-24-2014
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The ability of cells to respond and survive stressful conditions is determined, in part, by the attachment of O-linked N-acetylglucosamine (O-GlcNAc) to proteins (O-GlcNAcylation), a post-translational modification dependent on glucose and glutamine. This study investigates the role of dynamic O-GlcNAcylation of mesothelial cell proteins in cell survival during exposure to glucose-based peritoneal dialysis fluid (PDF). Immortalized human mesothelial cells and primary mesothelial cells, cultured from human omentum or clinical effluent of PD patients, were assessed for O-GlcNAcylation under normal conditions or after exposure to PDF. The dynamic status of O-GlcNAcylation and effects on cellular survival were investigated by chemical modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAc levels. Viability was decreased by reducing O-GlcNAc levels by DON, which also led to suppressed expression of the cytoprotective heat shock protein 72. In contrast, increasing O-GlcNAc levels by PUGNAc or alanyl-glutamine led to significantly improved cell survival paralleled by higher heat shock protein 72 levels during PDF treatment. Addition of alanyl-glutamine increased O-GlcNAcylation and partly counteracted its inhibition by DON, also leading to improved cell survival. Immunofluorescent analysis of clinical samples showed that the O-GlcNAc signal primarily originates from mesothelial cells. In conclusion, this study identified O-GlcNAcylation in mesothelial cells as a potentially important molecular mechanism after exposure to PDF. Modulating O-GlcNAc levels by clinically feasible interventions might evolve as a novel therapeutic target for the preservation of peritoneal membrane integrity in PD.
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WAVE1 mediates suppression of phagocytosis by phospholipid-derived DAMPs.
J. Clin. Invest.
PUBLISHED: 05-02-2013
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Clearance of invading pathogens is essential to preventing overwhelming inflammation and sepsis that are symptomatic of bacterial peritonitis. Macrophages participate in this innate immune response by engulfing and digesting pathogens, a process called phagocytosis. Oxidized phospholipids (OxPL) are danger-associated molecular patterns (DAMPs) generated in response to infection that can prevent the phagocytic clearance of bacteria. We investigated the mechanism underlying OxPL action in macrophages. Exposure to OxPL induced alterations in actin polymerization, resulting in spreading of peritoneal macrophages and diminished uptake of E. coli. Pharmacological and cell-based studies showed that an anchored pool of PKA mediates the effects of OxPL. Gene silencing approaches identified the A-kinase anchoring protein (AKAP) WAVE1 as an effector of OxPL action in vitro. Chimeric Wave1(-/-) mice survived significantly longer after infection with E. coli and OxPL treatment in vivo. Moreover, we found that endogenously generated OxPL in human peritoneal dialysis fluid from end-stage renal failure patients inhibited phagocytosis via WAVE1. Collectively, these data uncover an unanticipated role for WAVE1 as a critical modulator of the innate immune response to severe bacterial infections.
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[Peritoneal dialysis from the beginnings up to today: which developments of the last decades were important?].
Wien Med Wochenschr
PUBLISHED: 03-13-2013
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During the past years new developments in peritoneal dialysis (PD) technique have resulted in continuous improvement of patient outcome. The importance of salt and fluid balance, residual renal function and peritoneal glucose load are of increasing interest, whereas small solute clearances have lost importance. In patients with high peritoneal transport rates automated PD (APD) is indicated. However, APD can also be chosen as initial PD treatment since recent studies show comparable or even better survival as compared to continuous ambulatory PD patients. Alternative PD solutions improve peritoneal ultrafiltration (icodextrin), reduce peritoneal glucose load (amino acid solution, icodextrin) and protect the peritoneal membrane (solutions with low concentration of glucose degradation products). Infection risk can be reduced when using antibiotic creams, but resistances should be considered. Ongoing studies will clarify if non-antibiotic agents, e.g. medihoney, are effective in preventing PD-associated infections. Due to these improvements PD and hemodialysis have become equivalent treatments.
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Comparative in vitro fungicidal activity of echinocandins against Candida albicans in peritoneal dialysis fluids.
Mycoses
PUBLISHED: 01-11-2013
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The peritoneal dialysis (PD)-associated peritonitis caused by fungi is a relatively rare, but very serious disease. PD fluids (PDFs) affect inhibitory efficacy on the microorganisms growth, which may compromise the affectivity of some antimicrobials. The purpose of this study was to investigate in vitro the fungicidal effectiveness of echinocandins in diverse PDFs. The fungicidal efficacy of caspofungin (CAS), anidulafungin (ANA), micafungin (MYC) against five clinical isolates of Candida albicans was studied in the different PDFs using time-kill curves. As control substance amphotericin B was used. Echinocandins showed slower and reduced killing of C. albicans in PDFs when compared with the time-kill curves in control bouillon. At concentration of 8 × minimal inhibitory concentration (MIC) the greatest reduction in the growth of C. albicans was seen by ANA in lactate-buffered Nutrineal PD4(®) with 1.1% amino acid (2.33 ± 0.52 log10 CFU ml(-1) ), and by CAS and MYC in lactate-buffered Dianeal PD4(®) with 1.36% glucose (2.36 ± 0.89 log10 CFU ml(-1) and 2.36 ± 0.99 log10 CFU ml(-1) respectively). Using high concentration of 128 × MIC echinocandins achieved fungicidal effect in all PDFs. PDFs may significantly impair the activities of echinocandins, but fungicidal activity of drugs can be achieved at high concentration of 128 × MIC.
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Use of sodium thiosulphate in a multi-interventional setting for the treatment of calciphylaxis in dialysis patients.
Nephrol. Dial. Transplant.
PUBLISHED: 01-04-2013
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Calciphylaxis is a life-threatening complication in patients with end-stage renal disease (ESRD). No established therapy exists so far. The aim of the present study was to determine the therapeutic response to a multi-interventional treatment regimen with consistent use of sodium thiosulphate (STS) in an Austrian cohort of calciphylaxis patients.
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Treatment with oral active vitamin D is associated with decreased risk of peritonitis and improved survival in patients on peritoneal dialysis.
PLoS ONE
PUBLISHED: 01-01-2013
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Peritonitis is a major complication of peritoneal dialysis (PD) being associated with hospitalization, catheter loss, technique failure, and increased mortality. Data on incidence rates and risk factors for peritonitis episodes vary between centers. In seven Austrian PD units clinical and laboratory data on each peritonitis episode were collected from all patients (n = 726) who performed PD between January 2000 and December 2009. The peritonitis incidence rate was 0.32 episodes/patient-year. In a multivariate analysis the risk of peritonitis was decreased by 57% in patients treated with oral active vitamin D (HR 0.43; 95% CI 0.28-0.64). Renal disease classified as "other or unknown" (HR 1.65; 95% CI 1.08-2.53) and serum albumin <3500 mg/dl (HR 1.49; 95% CI 1.04-2.15) were also associated with an increased risk of peritonitis. Albumin levels <3500 mg/dl (HR 1.89; 95% CI 1.13-3.17), age (HR 1.06 per year; 95% CI 1.03-1.09), and cardiomyopathy (HR 3.01; 95% CI 1.62-5.59) were associated with increased mortality, whereas treatment with oral active vitamin D was associated with a significantly lower risk of death (HR 0.46; 95% CI 0.27-0.81). In this retrospective multi-center study we identified several factors being related to increased risk of peritonitis in PD patients. Treatment with oral active vitamin D was identified as being independently associated with decreased risk of peritonitis, and decreased all-cause mortality in PD patients.
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Prevalence of NSF following intravenous gadolinium-contrast media administration in dialysis patients with endstage renal disease.
Eur J Radiol
PUBLISHED: 02-21-2009
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To evaluate the prevalence of nephrogenic systemic fibrosis (NSF) in a patient population being at highest risk for developing this disease and to evaluate possible risk factors.
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Prognosis in patients with congestive heart failure and subacute renal failure treated with hemodialysis.
Wien. Klin. Wochenschr.
PUBLISHED: 01-14-2009
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Renal dysfunction confers a grave prognosis for patients with congestive heart failure (CHF); even small increases in plasma creatinine are associated with excess mortality. Little, however, is known about prognostic indices and outcome in patients with CHF who (sub-)acutely progress to dialysis dependency.
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Pharmacokinetics of intraperitoneal and intravenous fosfomycin in automated peritoneal dialysis patients without peritonitis.
Antimicrob. Agents Chemother.
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Blood and dialysate concentrations of fosfomycin were determined after intravenous and intraperitoneal application of 4 mg/liter in patients undergoing automated peritoneal dialysis. Maximum serum concentrations after intravenous (287.75 ± 86.34 mg/liter) and intraperitoneal (205.78 ± 66.78 mg/liter) administration were comparable. Ratios of intraperitoneal to systemic exposure were 1.12 (intraperitoneal administration) and 0.22 (intravenous administration), indicating good systemic exposure after intraperitoneal application but limited penetration of fosfomycin into the peritoneal fluid after the intravenous dose.
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Rapid T-cell-based immunodiagnosis of tuberculous peritonitis in a peritoneal dialysis patient.
Scand. J. Urol. Nephrol.
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Tuberculous peritonitis is a rare complication during peritoneal dialysis (PD). This report presents the case of a patient with clinical signs and symptoms indicative of bacterial peritonitis, but without culture growth of conventional bacteria or fungi. Cytokine flow cytometry after overnight stimulation of cells from peripheral blood and the peritoneal dialysate with Mycobacterium tuberculosis (MTB)-specific antigens revealed a 40-fold increase in MTB-specific CD4 + T cells expressing interferon-? (IFN-?) in peritoneal fluid compared with blood, which was indicative of active tuberculosis (TB). The presence of TB was later confirmed by polymerase chain reaction and growth of MTB in culture of the dialysate. The case illustrates the usefulness of MTB-specific immunodiagnosis for the rapid identification of peritoneal TB in PD patients.
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