PubMed Health⌕ Search

Biomedical subjects

F M Zuyderhoudt

Publications and source records attributed to F M Zuyderhoudt.

At least 19 recordsLinked to original sources

Plasma lipid peroxides in murine sepsis--sex differences and effect of antioxidative/anti-inflammatory therapy.

In order to investigate the influence of antioxidative/anti-inflammatory combination therapy (AACT) with dimethyl sulfoxide (DMSO), chlorpromazine (CPZ) and vitamin E upon the activity of the inflammation, plasma lipid peroxide was measured as thiobarbituric acid reactive substance (TBARS) 12 hrs postoperatively in the modified cecal ligation sepsis model in the mouse. Significantly higher TBARS levels were found in the male control group (13.7 +/- 0.7 nmol MDA/ml) than in the female control group (11.6 +/- 0.6 nmol MDA/ml). The operated male group had significantly higher TBARS levels (16.2 +/- 0.6 nmol MDA/ml) than the unoperated male control group (13.7 +/- 0.7 nmol MDA/ml). No increase of TBARS levels was observed in the operated female group. Both male and female operated group, when postoperatively treated with AACT had the same TBARS level as the not operated male or female control group. Survival curves of operated male and female group did not demonstrate any significant difference. The survival was better in an operated male and an operated female group, when postoperatively treated with AACT. It was concluded that the applied TBARS test is too insensitive to follow the activity of the inflammation and has no predictive value for the outcome of sepsis in this model.

Animals↗

Alterations in the peritoneal transport of water and solutes during peritonitis in continuous ambulatory peritoneal dialysis patients.

The in situ intraperitoneal volume and the mass transfer area coefficients (MTC) of urea, lactate, creatinine, glucose, kanamycin, inulin, beta 2-microglobulin, albumin and IgG were studied in eight continuous ambulatory peritoneal dialysis (CAPD) patients. All patients were studied during a 4-h dialysis dwell, first during peritonitis and subsequently after recovery from the infection. The maximal intraperitoneal volume was reached at 68 min during peritonitis and at 150 min in the study after recovery (P less than 0.01), suggesting increased water transport during the infection. For all investigated solutes MTCs were higher in the presence of peritonitis than after recovery. This increase was most marked for the proteins (greater than 100%). The power curve relationships between MTCs and molecular weight indicated that peritoneal transport of the low- and middle-molecular weight solutes was determined by free diffusion and that the infection-induced rise was due to an increase in effective surface area. For protein transport restricted diffusion was found. The increase of this transport during peritonitis was probably caused by both a larger effective surface area and a higher vascular permeability.

Adult↗

Circadian rhythm of urinary beta 2 microglobulin excretion in patients with a nephrotic syndrome.

The changes in urinary beta 2 microglobulin excretion during the day were studied in 20 patients with a nephrotic syndrome under standardized conditions and compared with the known circadian variations in urinary albumin excretion in the same patients. Fifteen of the 20 patients (75%) had a circadian rhythm for beta 2 microglobulin in the urine. Phase as well as relative amplitude of the beta 2 microglobulin circadian rhythm varied between patients. In addition, its presence, normality, amplitude and phase were largely different from the albumin rhythm. Observations made in 10 healthy individuals suggest that day-night variability in the excretion of beta 2 microglobulin and albumin in the urine is also present in the absence of clinically important proteinuria. Circadian variations in urinary beta 2 microglobulin excretion are found in a majority of the patients with nephrotic syndrome and as they differ in several respects from the day-night fluctuation in urinary albumin excretion the mechanism is probably different.

Adolescent↗

The relationship between peritoneal glucose absorption and body fluid loss by ultrafiltration during continuous ambulatory peritoneal dialysis.

Eight continuous ambulatory peritoneal dialysis (CAPD) patients were studied during six consecutive days using dialysate with a different glucose concentration on each day. For all dialysate glucose concentrations ranging from 70 to 198 mmol/l, an inverse linear relationship was found between the percentage of absorbed glucose and the ultrafiltration rate. In each patient a linear correlation was demonstrated between the dialysate glucose concentration and the quantity of body fluid removed by ultrafiltration. Therefore the dialysate glucose concentration without net removal of fluid could be calculated for each patient: DGCUF = 0. This DGCUF = 0 is a parameter of the relationship between the transport of water and glucose over the peritoneal membrane and can thus be considered a marker of the individual ultrafiltration. The calculated DGCUF = 0 was compared with DGCUF = 0 predicted from the glucose absorption using the equation as derived from our data: DGCUF = 0 (mmol/l) = 2.1 X glucose absorption (%) -67 (mmol/l). As marked day to day variations were found, the results of these predicted DGCUF = 0 should be interpreted cautiously when used for long-term follow-up of peritoneal permeability in CAPD patients.

Adult↗

Histophotometric estimation of volume density of collagen as an indication of fibrosis in rat liver.

The development of fibrosis in the liver of 16 rats treated for 1, 2, 3 or 4 weeks with CCl4, has been followed with chemical hydroxyproline determination and histophotometric analysis of histological sections stained with Sirius Red F3BA in saturated aqueous picric acid. The readings were taken with a scanning and integrating microphotometer and corrected for picric acid absorbance as a measure for mean protein mass per unit area of the section. It appears that the integrated absorbance readings of Sirius Red absorbing material in the section show a highly significant correlation with the hydroxyproline determinations. It is concluded that picrosirius photometry can be used to give a measure of the volume density of collagen in sections. An advantage of the photometric assay is that measurements are taken on the basis of the microscopic image, so that it is also possible to estimate collagen density in a selected area, e.g. a tumour formation amidst normal tissue, or to exclude necrotic areas.

Animals↗

Mechanisms by which acute phase proteins enhance development of liver fibrosis: effects on collagenase and prolyl-4-hydroxylase activity in the rat liver.

Previous experiments showed that the presence of high levels of acute phase reactants (APR) enhance CCl4-induced liver fibrosis in the rat. A high correlation was found between the degree of fibrosis and alpha 2-macroglobulin of the rat (alpha 2-macrofetoprotein, alpha M-FP) used for monitoring the acute phase response. This acute phase reaction was provoked by epinephrine just before CCl4 treatment was started. In the present study we analyzed the effect of APR by repeating these experiments and estimating liver neutral collagenase with a synthetic substrate and endogenous collagen as a substrate, and liver prolyl-4-hydroxylase. A strong depression of liver collagenase activity was found in rats with a preceding acute phase reaction contrary to the rats that underwent CCl4 treatment only. A high level of alpha M-FP correlated negatively with collagenase activity. Also in vitro alpha M-FP proved to inhibit collagenase activity. Prolyl-4-hydroxylase was increased in the rats during acute phase reaction and correlated highly and positively with alpha M-FP, haptoglobin, and ceruloplasmin. Thus high levels of APR promote development of CCl4-induced fibrosis, partly by anticollagenase activity and partly because of enhancement of prolyl-4-hydroxylase activity. The latter phenomenon can also be explained by the presence of APR, but this has to be proved.

Acute-Phase Proteins↗

Simple assessment of the efficacy of peritoneal transport in continuous ambulatory peritoneal dialysis patients.

The efficacy of peritoneal transport was assessed in 13 permeability studies in 11 continuous ambulatory peritoneal dialysis (CAPD) patients. During each study the in situ intraperitoneal volume was measured as well as the dialysate and plasma concentrations of various solutes with a molecular weight range from 60 to 5,500. As clearance estimations are unsuitable for the purpose of permeability studies, mass transfer area coefficients were used. By applying a simple mathematical model assuming first-order kinetics, these coefficients were calculated for urea, lactate, creatinine, glucose, kanamycin, and inulin. The accuracy of the calculations is indicated by their r values. After pooling these correlation coefficients, the mean approached 1.00 for all solutes with high confidence limits, indicating the usefulness of the model. A further simplification was tested using only an initial- and end-dialysate sample and two blood samples, without the measurement of the in situ intraperitoneal volume. Except for inulin the results of this simplification correlated well with the results described above. The reproducibility of the simplified mass transfer area coefficient calculations was investigated on 15 occasions in 3 other CAPD patients. The coefficients of variation of low molecular weight solutes varied between 15 and 20%. It is concluded that mass transfer area coefficient estimations using the latter method can be performed in any CAPD patient and probably yield sufficient information to establish the efficacy of the membrane transport mechanism during clinical follow-up.

Adult↗

Peritoneal permeability to proteins in diabetic and non-diabetic continuous ambulatory peritoneal dialysis patients.

Peritoneal permeability to proteins was measured in diabetic and non-diabetic continuous ambulatory peritoneal dialysis patients during peritonitis and control periods. Clearances of albumin, transferrin, IgG, C3 and alpha 2-macroglobulin appeared to decrease as molecular weight increased. This relationship could be described by a power curve fit. The decrease was more than could be explained by differences in free diffusion only, indicating a size-selective barrier in the peritoneum. For all measured proteins clearances were higher in the diabetic patients. This may reflect a generally increased permeability due to their microangiopathy. The largest increase in protein loss and protein clearances was found during peritonitis. Our results do not suggest increased local production of any of the investigated proteins during the inflammation. Therefore, an increase in either peritoneal permeability or effective surface area or both is the most likely explanation. It is concluded in this study that peritoneal protein clearances are dependent on their molecular weight and that they are proportionally increased in patients with diabetes and during peritonitis.

Adult↗

Formulation of a stable p-acetylaminohippurate infusion fluid and determination of the serum concentrations.

An infusion fluid with p-acetylaminohippurate (PACAH) was formulated and a method for analysis of PACAH in serum, urine and infusion fluid based on reversed phase HPLC was developed. No significant degradation could be observed after steam sterilization for twenty minutes at 120 degrees C. From the results of an investigation of the degradation rate at elevated temperatures a negligible loss of content during storage for three years at 20 degrees C could be predicted. Steady state serum concentrations of PACAH after constant infusion were determined.

Aminohippuric Acids↗

Ferritin in liver, plasma and bile of the iron-loaded rat.

Rats were loaded with iron. With overload, up to a 10-fold increase of the iron and ferritin protein content of the livers was measured. The plasma ferritin concentration increased gradually with the ferritin concentration in the liver. The ferritin concentration in the bile increased also and was in the same range as in the plasma. The ratio plasma ferritin concentration to bile ferritin concentration in individual rats decreased in the case of considerable iron overload. After intravenous injection of liver ferritin, less than 2% of the ferritin concentration that disappeared from the blood was found to be in the bile. Isoelectric focussing revealed that the microheterogeneity of liver and bile ferritin were identical, but slightly different from plasma ferritin. These results indicate that ferritin was not solely leaking from the plasma to the bile. Together with ferritin, iron accumulated in the bile. The iron content of the bile ferritin was in the same range as in fully iron-loaded liver ferritin. It is likely that ferritin in the bile is excreted by the liver and consists of normal iron-loaded liver ferritin molecules. In all circumstances, the amount of iron in the bile was much higher than could be accounted for by transport by the bile ferritin. The ferritin protein to iron ratio in the bile was 0.1-1.2, which was in the same range as was measured in isolated lysosomal fractions of the liver. Those results agree with the supposition that ferritin and iron in the bile are excreted by the liver though lysosomal exocytosis.

Alanine Transaminase↗

The microheterogeneity of human liver and serum ferritins measured on minute amounts of ferritin in crude samples.

A method is presented to measure the microheterogeneity of ferritin in micrograms amounts, without purifying the samples extensively. Ferritin-containing samples such as serum and homogenized liver-biopsy specimens were mixed with Sephadex G-75 and ampholines. Isoelectric focussing was performed and the pH gradient in the Sephadex was measured. The Sephadex was divided into predetermined pH ranges and the ferritin eluted from these fractions. Ferritin concentration was measured by an enzyme-linked immunosorbent assay. The method proved to be reproducible. The isoferritin profiles of different human serum and liver tissue samples were quite variable. In most cases serum ferritins focussed between approximately pH 5.5 and pH 4.9 and liver ferritins between approximately pH 5.8 and pH 5.3. We examined whether there was a similarity in the isoferritin patterns of serum and liver of distinct patients. We also studied liver tissue and serum from a patient with haemochromatosis and from a child with iron overload of unknown origin. In the serum of our patients the isoferritin pattern had shifted to lower pI when compared with that found in liver tissue. Only in the case of a patient with transfusion iron overload were basic isoferritins measured in the serum. In this case no liver biopsy specimen was available for comparison.

Ferritins↗

Influence of liver isoferritin profile on quantitative measurement of total ferritin protein in human liver, with emphasis on iron overload.

Ferritin was isolated from normal human liver and from iron-loaded human liver by gel chromatography and by ultracentrifugation. From each of these ferritin batches several isoferritin fractions were isolated by preparative isoelectric focusing. It was our aim to have at our disposal isoferritin fractions with relatively large pI ranges but distinctly different isoferritin profiles on analytical isoelectric focusing. These fractions were compared for their immunoreactivity. The total protein in the isoferritin fractions was measured by the nitrogen content. The immunoreactivity of the isoferritin fractions was measured as the ratio of the reaction in immunoassays to the nitrogen content of these fractions. We used radial immunodiffusion and enzyme-linked immunoassay to measure immunoreactivity. The immunoreactivity did not change obviously with the isoferritin composition of the isolated fractions. It is concluded that pathological changes in the isoferritin composition that might occur in liver ferritin during iron overload does not significantly influence the quantitative measurement of liver ferritin protein by immunological methods.

Electrophoresis, Polyacrylamide Gel↗

Some aspects of iron metabolism during acute viral hepatitis.

In the acute phase of acute viral hepatitis high serum iron and serum ferritin levels were found in all patients. The normalisation of the serum ferritin concentration parallelled that of the serum glutamic pyruvic transaminase activity. However serum iron levels remained elevated for a long period of time. Chemical analysis of liver tissue showed a low total liver depot iron concentration during the first two weeks of the disease, indicating that the high serum iron levels are caused by iron liberation from disintegrated hepatocytes. Patients studied after two weeks showed higher liver iron concentrations, in particular the non-ferritin iron fraction, reflecting iron accumulation in the reticulo-endothelial system. Indeed, histological examination in the patients studied after two weeks showed sinusoidal lining cell siderosis in addition to "diffuse iron" in clusters lining cells which in electron microscopical studies proved to be macrophages. These cells showed a positive immunohistological reaction for ferritin protein. It is suggested that during acute viral hepatitis two mechanisms act together, i.e. changes in iron metabolism caused by damage of the main iron depot organ (specific liver pathology) and changes in iron metabolism common to all infectious processes.

Acute Disease↗

Iron mobilisation with chelating agents during acute viral hepatitis.

During acute viral hepatitis, disturbances in iron metabolism occur. To obtain more insight into this, DFO and DTPA induced urinary iron excretion was studied during acute viral hepatitis. It was found that liver cell damage enhances iron excretion, in proportion to the extent of liver cell disintegration: a highly significant correlation was shown between the DFO as well as DTPA induced urinary iron excretion, and the SGPT. Also, a correlation existed between sideruria and the serum iron level, as well as with the serum bilirubin concentration, provided the test was performed within 10 days after the onset of the jaundice. It is suggested that during liver cell damage, iron, which is liberated during ferritin catabolism, forming a transit pool within the hepatocyte and/or at the cell membrane, is the immediate source of iron donation to DFO and/or DTPA. The practical importance for interpretation of iron mobilisation tests is pointed out.

Alanine Transaminase↗