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Biomedical subjects

S Shaldon

Publications and source records attributed to S Shaldon.

At least 91 records · Page 5Linked to original sources
PubMed1988

Detection of endotoxin-like interleukin-1-inducing activity during in vitro dialysis.

In order to study the integrity of dialysis membranes to pyrogens, the dialysate side of a closed loop hemodialysis (HD) circuit was challenged with E. coli microfiltrate containing 500 ng/ml endotoxin. Three solutions, a) tissue culture medium/saline, b) 5% human serum albumin, and c) 10% fresh human plasma, were circulated in the blood loop for five hours. Samples drawn from the blood side were assayed for interleukin-1 (IL-1)-inducing activity on human mononuclear cells (MNC) in vitro. No IL-1-inducing substances were detected when saline or culture medium was circulated in the blood loop. Circulating 5% human serum albumin revealed IL-1-inducing activity in the samples drawn only after five hours of HD. However, the addition of 10% fresh human plasma to the blood side resulted in the appearance of an IL-1-inducing substance(s) after 15 minutes of HD. After 30 minutes, maximum IL-1-inducing activity was observed (control stimulation index, 3.30 +/- 0.67 SEM vs. 7.59 +/- 1.50, P less than 0.02). The IL-1-inducing activity of the samples was completely inhibited by polymyxin B, a cationic antibiotic which blocks the IL-1-inducing activity of endotoxin. Additional experiments demonstrated that in vitro MNC IL-1-production induced by the same E. coli microfiltrate is enhanced in the presence of 10% plasma. These studies demonstrate that: (a) in the presence of plasma, IL-1-inducing factors pass into the blood compartment of a dialysis system challenged with bacterial pyrogen; and (b) MNC production of IL-1 is enhanced in the presence of plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Endotoxins↗
PubMed1988

Plasma interleukin-1 activity during hemodialysis: the influence of dialysis membranes.

Plasma interleukin-1 (IL-1) activity was measured in 7 stable ESRD patients on regular hemodialysis for no less than 5 months. Predialysis levels were significantly raised compared to 8 normal control subjects. During hemodialysis with four different membranes, plasma IL-1 activity rose with Cuprophan and Hemophan and was unchanged or reduced with Gambrane and Polysulfon. In spite of these differences, body temperature rose in all forms of hemodialysis. Factors responsible for the predialysis elevation included the absence of renal function and/or the repeated stimulus of human blood monocytes by hemodialysis. In view of the uniform increase of body temperature during hemodialysis, the differences in changes of plasma IL-1 activity observed with the various membranes may not be caused by a variable stimulation of monocytes but rather by the presence or absence of the membrane's ability to remove and/or absorb IL-1. Thus, the consequences of monocyte hemodialysis stimulation may be obtained locally, even in the presence of unchanged or reduced plasma IL-1 activity.

Adult↗
PubMed1988

Beta 2-microglobulin kinetics during haemofiltration.

To study the kinetics of beta 2-microglobulin during haemofiltration, seven patients with end-stage renal failure were treated with the AN 69 (acrylonitrile), Duo-Flux (cellulose acetate) and F 60 (polysulphone) haemofilter. Low beta 2-microglobulin sieving coefficients and a highly negative filter mass balance error were observed during the initial phase of treatment with AN 69 but not with Duo-Flux or F 60, indicating a high degree of beta 2-microglobulin adsorption by AN 69. Total removal of beta 2-microglobulin was calculated by addition of the total amount adsorbed by the membrane and the total amount recovered in the collected ultrafiltrate. With AN 69 and F 60, total removal of beta 2-microglobulin amounted to 393 +/- 135 (SD) and 316 +/- 35 mg per treatment, while total removal with Duo-Flux was 242 +/- 79 mg per treatment. Thus, highly permeable membranes such as AN 69 or F 60 used in a haemofiltration mode may nearly balance the presumed generation of beta 2-microglobulin in uraemic patients. During treatment, an increase of the calculated beta 2-microglobulin distribution volume occurred with all three membranes, probably representing extra-to-intracellular water shifts. The water shifts occurring during haemofiltration reduce the value of precision of beta 2-microglobulin kinetics and limit the value of the plasma level decrease as an index of beta 2-microglobulin removal.

Acrylonitrile↗
PubMed1988

Studies on the ability of hemodialysis membranes to induce, bind, and clear human interleukin-1.

Interleukin-1 (IL-1) is a polypeptide cytokine predominantly produced by monocytes in response to injury or infection. Effects of IL-1 such as fever, acute phase protein synthesis, hypotension, and loss of body mass are complications of hemodialysis. Endotoxin-contaminated dialysate fluid, sodium acetate as a dialysate buffer, and activated complement can induce IL-1 during hemodialysis. In the present study, we investigated the intrinsic property of hemodialysis membranes to stimulate human blood mononuclear cells (MNC) to produce IL-1. Incubation of MNC on sheets of two commonly used hemodialysis membranes, regenerated cellulose (RC) and polyacrylonitrile (PAN) resulted in significant induction of IL-1 in the absence of endotoxin or complement. Production of intracellular and extracellular IL-1 was greater in MNC exposed to PAN compared with RC (p less than 0.01). Similar results were obtained when MNC were exposed to strips of hemodialysis membranes in rotating tubes. However, compared with RC, PAN binds significant amounts of human IL-1. In a model of in vitro hemodialysis, radiolabeled recombinant human IL-1 was added to the blood compartment of a PAN and a RC dialyzer. Forty percent of radiolabeled IL-1 bound to the PAN dialyzer membrane compared with 10% to the membrane of a RC dialyzer. In addition, 22% of radiolabeled IL-1 was found in the dialysate compartment of a PAN dialyzer after 1 hour whereas 1% was found in the dialysate side of a RC dialyzer; these results were confirmed by measuring bioactivity of IL-1. These studies demonstrate the intrinsic property of hemodialysis membranes to stimulate human IL-1 production; in addition they establish that dialysis membranes differ in their ability to bind and clear IL-1.

Acrylic Resins↗
PubMed1987

Enhancement of in-vitro human interleukin-1 production by sodium acetate.

Human blood monocytes were incubated in vitro in the presence of various concentrations of sodium acetate or sodium chloride or with medium alone. Intracellular and extracellular levels of interleukin-1 (IL-1) were measured. The production of intracellular IL-1 and the release of extracellular IL-1 were higher in the presence of acetate than in the presence of chloride or in medium alone. The concentrations of acetate used were comparable to those encountered by blood monocytes on the surface of haemodialysis membranes. Since complications of peritoneal dialysis, such as loss of ultrafiltration and progressive fibrosis of the peritoneum, have been associated with the use of sodium acetate as the exchange-fluid buffer, these results suggest that the widespread use of sodium acetate as a buffer during haemodialysis may be contraindicated.

Acetates↗
PubMed1987

Ultrafiltration to reject human interleukin-1-inducing substances derived from bacterial cultures.

Interleukin-1 (IL-1), a polypeptide cytokine, is an important mediator of host responses to infection and injury. Picogram per milliliter concentrations of bacterial products (endo- or exotoxins) stimulate human monocytes to produce IL-1 in vitro. The design of this study was based on the clinical model of bacterial contamination of fluid intended to be directly injected into humans. Physiologic saline contaminated with bacterial toxins was passed through a hollow fiber ultrafilter, and the ultrafiltrates were tested for their ability to induce human IL-1 production. The ultrafiltrates were added directly to freshly obtained human blood mononuclear cells, and after 24 h of incubation the supernatant media were assayed for the presence of IL-1. The results indicate that the IL-1-inducing material(s) present in bacterial cultures of gram-negative organisms is rejected by a factor of 100 to 100,000 by molecular size exclusion and by absorption; rejection is sustained for at least 32 liters of fluid; the rejection of Limulus-reactive material by the ultrafilter is greater for purified endotoxin than for native endotoxins derived from live bacterial cultures; and nonendotoxin IL-1-inducing toxins (molecular weight, 24,000) from Staphylococcus aureus are not rejected or absorbed. These results demonstrate that there is a considerable margin of safety with the ultrafiltration method and that it can be applied to clinical situations.

Bacterial Toxins↗