Albumin has been considered a "sacrificial plasma antioxidant" due to the high ... more Albumin has been considered a "sacrificial plasma antioxidant" due to the high reactivity of the protein sulfhydryl groups with oxidants such as hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). Based on its large quantity and high turnover. It is considered as one of the most important plasma antioxidants for protecting key cellular and regulatory proteins. Since hemodialysis patients have lower overall levels of albumin and possible protein modifications due to uremic toxins, we investigated whether modifications by various uremic toxins would affect the susceptibility of albumin to an oxidative challenge. We incubated bovine serum albumin in the presence of carboxymethyllysine (CML) (10 micromol/L(-1) mmol/L), methyl glyoxal (50 micromol/L(-5) mmol/L), p-cresol (100 micromol/L-10 mmol/L) or hippuric acid (200 micromol/L-20 mmol/L) for 16 hours at 37 degrees C and then subsequently added 0.5 mmol/L(-1) mmol of H2O2/HOCl. We measured the extent of protein modification by the loss of protein sulfhydryl groups, dityrosine formation and the formation of advanced oxidation protein products (AOPP). Incubation of albumin with the uremic toxins caused a loss of protein sulfhydryl groups and an increase in dityrosines and AOPP. The presence of uremic toxins had no effect on the loss of protein sulfhydryl groups after addition of H2O2/HOCl; however, low levels of CML, p-cresol and methyl glyoxal inhibited the formation of AOPP and dityrosines. We suggest that uremic toxins may possibly play a role in mediating free radical initiated protein damage.
Background On-line hemodiafiltration is gaining popularity due to increasing evidence of clinical... more Background On-line hemodiafiltration is gaining popularity due to increasing evidence of clinical benefits however it also requires strict attention to hygiene and safety as notable quantities of liquid are reinfused into the patient. Although most centers are improving their attention to water quality, a frequent concern is the inadvertent or accidental contamination of water and whether the redundant safety controls are sufficient to protect the patient. In the present study, in order to simulate a worst-case safety condition, we tested in vitro the reliability of paired hemodiafiltration – (PHF), under low, moderate and high bacterial contamination of the water supply. Tests were performed using various bacterial concentrations (range 85–2000 cfu/mL) of Pseudomonas Aeruginosa. Samples were analyzed from different sites throughout the entire on-line hemodiafiltration circuit for bacteria endotoxin, fungus and ability to stimulate whole blood production of TNF α. Results In the in vitro contamination study, with the three bacterial concentrations tested at various points of the circuit, bacteria were below the level of detection and endotoxins were < 0.01 UE/mL. Addition of dialysate samples taken after the first stage of microfiltration, as well as after the first and second stage of ultrafiltration and incubated with whole blood were not associated with stimulated production of TNFα. Conclusions PHF appeared to be a safe and feasible method for on-line hemodiafiltration even in the unforeseen presence of bacterial contamination of the feed water or water distribution system.
ABSTRACT Critically ill patients are increasingly being treated with continuous haemofiltration a... more ABSTRACT Critically ill patients are increasingly being treated with continuous haemofiltration and its derived techniques, now grouped under the term &#39;continuous renal replacement therapies&#39; (CRRT). CRRT can provide adequate blood purification and correction of electrolyte derangements. They also seem to prevent further injury to the patient by maintaining a stable level of homoeostasis. Recently, it has been proposed that CRRT could be used in the treatment of neonates, of patients with heart disease and, finally, of septic patients. It has been hypothesised that continuous therapies might contribute to the removal of noxious substances in the middle molecular weight range such as cytokines or autacoids. According to these new proposals, technical developments are making available new forms of treatment, new materials and specially designed machines.
Sepsis is the leading cause of acute renal failure and mortality in intensive care units [1–3]. I... more Sepsis is the leading cause of acute renal failure and mortality in intensive care units [1–3]. It generally develops as a result of the host response to infection [4]. The pathogenesis of sepsis represents a complex mosaic of interconnected events in respect to which ...
Rapid and reliable exclusion of acute myocardial infarction during emergency department triage is... more Rapid and reliable exclusion of acute myocardial infarction during emergency department triage is an important clinical need. The purpose of this study was to evaluate the potential role of copeptin, a marker of acute endogenous stress, together with high sensitive troponin-I for a rapid and early rule-out of acute myocardial infarction. Copeptin and myoglobin were measured in 80 subjects presenting to the emergency department with chest pain and symptoms suggestive of acute myocardial infarction, 46 patients had a negative high sensitive troponin-I concentration at presentation, 3, 6 and 12 hours; whereas 34 patients had negative or very low high sensitive troponin-I at presentation, but rising troponin values at 3, 6 and 12 hours. Copeptin was significantly higher in patients with evidence of myocardial damage (median 92.2 pmol/L vs 8.5 pmol/L, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). The area under the receiver-operating characteristic curve (AUC) for copeptin at initial presentation was 0.86 (95 % confidence interval, CI: 0.76 to 0.93), which was significantly higher than 0.68 (95% CI: 0.57 to 0.78, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) for myoglobin but not significantly different from 0.88 (95% CI: 0.79 to 0.93) for high sensitive troponin-I. The combination of high sensitive troponin-I and copeptin resulted in an AUC of 0.94 (95% CI: 0.86 to 0.98), while the combination of high sensitive troponin-I and myoglobin results in an AUC of 0.89 (95% CI: 0.81 to 0.95). Copeptin concentrations are more sensitive than myoglobin as an early marker of myocardial damage. Although copeptin provides significant incremental value on top of high sensitivity troponin-I, myoglobin does not.
Albumin has been considered a &quot;sacrificial plasma antioxidant&quot; due to the high ... more Albumin has been considered a &quot;sacrificial plasma antioxidant&quot; due to the high reactivity of the protein sulfhydryl groups with oxidants such as hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). Based on its large quantity and high turnover. It is considered as one of the most important plasma antioxidants for protecting key cellular and regulatory proteins. Since hemodialysis patients have lower overall levels of albumin and possible protein modifications due to uremic toxins, we investigated whether modifications by various uremic toxins would affect the susceptibility of albumin to an oxidative challenge. We incubated bovine serum albumin in the presence of carboxymethyllysine (CML) (10 micromol/L(-1) mmol/L), methyl glyoxal (50 micromol/L(-5) mmol/L), p-cresol (100 micromol/L-10 mmol/L) or hippuric acid (200 micromol/L-20 mmol/L) for 16 hours at 37 degrees C and then subsequently added 0.5 mmol/L(-1) mmol of H2O2/HOCl. We measured the extent of protein modification by the loss of protein sulfhydryl groups, dityrosine formation and the formation of advanced oxidation protein products (AOPP). Incubation of albumin with the uremic toxins caused a loss of protein sulfhydryl groups and an increase in dityrosines and AOPP. The presence of uremic toxins had no effect on the loss of protein sulfhydryl groups after addition of H2O2/HOCl; however, low levels of CML, p-cresol and methyl glyoxal inhibited the formation of AOPP and dityrosines. We suggest that uremic toxins may possibly play a role in mediating free radical initiated protein damage.
Background On-line hemodiafiltration is gaining popularity due to increasing evidence of clinical... more Background On-line hemodiafiltration is gaining popularity due to increasing evidence of clinical benefits however it also requires strict attention to hygiene and safety as notable quantities of liquid are reinfused into the patient. Although most centers are improving their attention to water quality, a frequent concern is the inadvertent or accidental contamination of water and whether the redundant safety controls are sufficient to protect the patient. In the present study, in order to simulate a worst-case safety condition, we tested in vitro the reliability of paired hemodiafiltration – (PHF), under low, moderate and high bacterial contamination of the water supply. Tests were performed using various bacterial concentrations (range 85–2000 cfu/mL) of Pseudomonas Aeruginosa. Samples were analyzed from different sites throughout the entire on-line hemodiafiltration circuit for bacteria endotoxin, fungus and ability to stimulate whole blood production of TNF α. Results In the in vitro contamination study, with the three bacterial concentrations tested at various points of the circuit, bacteria were below the level of detection and endotoxins were < 0.01 UE/mL. Addition of dialysate samples taken after the first stage of microfiltration, as well as after the first and second stage of ultrafiltration and incubated with whole blood were not associated with stimulated production of TNFα. Conclusions PHF appeared to be a safe and feasible method for on-line hemodiafiltration even in the unforeseen presence of bacterial contamination of the feed water or water distribution system.
ABSTRACT Critically ill patients are increasingly being treated with continuous haemofiltration a... more ABSTRACT Critically ill patients are increasingly being treated with continuous haemofiltration and its derived techniques, now grouped under the term &#39;continuous renal replacement therapies&#39; (CRRT). CRRT can provide adequate blood purification and correction of electrolyte derangements. They also seem to prevent further injury to the patient by maintaining a stable level of homoeostasis. Recently, it has been proposed that CRRT could be used in the treatment of neonates, of patients with heart disease and, finally, of septic patients. It has been hypothesised that continuous therapies might contribute to the removal of noxious substances in the middle molecular weight range such as cytokines or autacoids. According to these new proposals, technical developments are making available new forms of treatment, new materials and specially designed machines.
Sepsis is the leading cause of acute renal failure and mortality in intensive care units [1–3]. I... more Sepsis is the leading cause of acute renal failure and mortality in intensive care units [1–3]. It generally develops as a result of the host response to infection [4]. The pathogenesis of sepsis represents a complex mosaic of interconnected events in respect to which ...
Rapid and reliable exclusion of acute myocardial infarction during emergency department triage is... more Rapid and reliable exclusion of acute myocardial infarction during emergency department triage is an important clinical need. The purpose of this study was to evaluate the potential role of copeptin, a marker of acute endogenous stress, together with high sensitive troponin-I for a rapid and early rule-out of acute myocardial infarction. Copeptin and myoglobin were measured in 80 subjects presenting to the emergency department with chest pain and symptoms suggestive of acute myocardial infarction, 46 patients had a negative high sensitive troponin-I concentration at presentation, 3, 6 and 12 hours; whereas 34 patients had negative or very low high sensitive troponin-I at presentation, but rising troponin values at 3, 6 and 12 hours. Copeptin was significantly higher in patients with evidence of myocardial damage (median 92.2 pmol/L vs 8.5 pmol/L, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). The area under the receiver-operating characteristic curve (AUC) for copeptin at initial presentation was 0.86 (95 % confidence interval, CI: 0.76 to 0.93), which was significantly higher than 0.68 (95% CI: 0.57 to 0.78, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) for myoglobin but not significantly different from 0.88 (95% CI: 0.79 to 0.93) for high sensitive troponin-I. The combination of high sensitive troponin-I and copeptin resulted in an AUC of 0.94 (95% CI: 0.86 to 0.98), while the combination of high sensitive troponin-I and myoglobin results in an AUC of 0.89 (95% CI: 0.81 to 0.95). Copeptin concentrations are more sensitive than myoglobin as an early marker of myocardial damage. Although copeptin provides significant incremental value on top of high sensitivity troponin-I, myoglobin does not.
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