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Biomedical subjects

D Raichvarg

Publications and source records attributed to D Raichvarg.

At least 19 recordsLinked to original sources
PubMed1996

Characterization of lipoproteins during human cholestasis.

We have characterized changes in lipoproteins from cholestatic individuals and reproduced them by incubating lipoproteins from healthy individuals with cholic acid. The cholestatic patients showed an increase in low density lipoprotein (LDL) (>85%), with a smaller proportion of esterified cholesterol, and a fall in high density lipoprotein (HDL) (<10%), with a larger proportion of phospholipids. The protein composition of cholestatic HDL1 was characterized by a smaller proportion of apo A (I, II) and a prominent apo E fraction (39% vs. 9%). These changes involved an increase in degree of molecular packing (order) of HDL1. The addition of cholic acid to serum from healthy individuals altered the lipoprotein distribution, with an increase in LDL, the disappearance of HDL2 and HDL3 and the appearance of HDL1. These HDL1 were characterized by increased phospholipid and reduced apo AI fractions. They also showed a lower density and appeared as spherical particles in contrast to cholestatic HDL. Incubation of healthy HDL with cholic acid in vitro reproduces some of the alteration observed in cholestatic HDL.

Chemical Phenomena↗
PubMed1994

Effects of alpha-1 acid glycoprotein on human polymorphonuclear neutrophils: influence of glycan microheterogeneity.

The biological functions of alpha-1 acid glycoprotein (AGP) are poorly understood but appear to depend on glycan microheterogeneity. Variations of AGP glycan structure (in terms of concanavalin A (ConA) reactivity) have been observed during the inflammatory process. We studied these modifications in AGP from patients with chronic renal impairment and investigated the effects of AGP microheterogeneity on healthy polymorphonuclear leukocyte (PMN) chemotaxis and oxidative metabolism. AGP was extracted by a two-step procedure from sera from ten patients with various degrees of renal impairment, selected according to AGP glycan heterogeneity determined by crossed immunoaffinity electrophoresis with ConA. AGP (0.5 g/l) significantly inhibited the chemotactic response of PMN to formyl-methionyl-leucyl-phenylalanine (10(-7) mol/l) and complement fraction C5a, regardless of ConA reactivity. AGP also inhibited superoxide anion generation in response to phorbol myristate acetate (10(-7) mol/l). After stimulation by opsonized zymosan (1 g/l), the effect of AGP appeared to depend on its glycan structure (r = 0.70, P < 0.05), decreasing with ConA non-reactivity. These data suggest that AGP can down-regulate neutrophil responsiveness, an effect that depends in part on its glycan microheterogeneity. Alterations of AGP microheterogeneity in various pathological states, particularly renal failure, may be related to the inflammatory process.

Adult↗
PubMed1994

In vitro effect of cetirizine on PGE2 release by rat peritoneal macrophages and human monocytes.

Cetirizine was first described as a specific anti-H1 molecule displaying potent antiallergic activity. It was later found that its pharmacological properties extended to cellular actions as on eosinophil recruitment at inflammatory sites in allergic patients. Monocytes and macrophages participate in allergic mechanisms, particularly through high affinity H1 and H2 membrane receptors and generation of pro- and anti-inflammatory agents; among them histamine-induced factors, IL-1 and prostanoids are of importance. The aim of this work was to investigate the effect exerted by various concentrations of cetirizine (0.1-10 micrograms/ml) applied in vitro to human monocytes and peritoneal rat macrophages cultured for 24 h. Peritoneal macrophages were collected either from normal or experimentally inflamed rats. Human monocytes, isolated from peripheral blood, were studied either in a resting state or after stimulation by LPS from Escherichia coli (1 and 10 micrograms/ml). Cetirizine (10 micrograms/ml) significantly enhanced IL-1 release by human monocytes stimulated by a weak LPS concentration (1 microgram/ml) but could not modify the maximal increase of IL-1 release induced by 10 micrograms/ml of LPS. It did not exert any effect on resting cells. Cetirizine (0.1-10 micrograms/ml) enhanced PGE2 release by resting human monocytes. Concentrations of 1 and 10 micrograms/ml enhanced PGE2 release by LPS-stimulated monocytes, and by healthy and inflamed rat macrophages. This effect was concentration-dependent. Our findings point to an anti-inflammatory action of cetirizine via PGE2 release and histamine H2 interactions. Cetirizine did not directly modify IL-1 generation by resting monocytes but the IL-1 production observed after LPS stimulation could promote the mechanisms by which PGE2 is released.

Animals↗
PubMed1994

Effects of low-density lipoproteins on polymorphonuclear leukocyte functions in vitro.

In the circulation, human polymorphonuclear leukocytes (PMN) are exposed to various factors, such as lipoproteins, which could alter their metabolic and functional characteristics. In this work, the effects of low-density lipoproteins (LDL) on PMN oxidative metabolism and migration were studied in vitro. LDL stimulated PMN superoxide generation. This effect lasted for 15-20 min and was concentration-dependent. Staurosporine, a potent inhibitor of protein kinase C, did not suppress this stimulating effect. The chemotactic response of PMN to formyl-methionyl-leucyl-phenylalanine and C5a was inhibited by LDL and this effect was conserved after trypsination of LDL. LDL from normolipidemic subjects were more potent than LDL from hypertriglyceridemic subjects for both effects. LDL had no effect on superoxide generation by opsonized zymosan-stimulated PMN. These data showed that PMN responses may be modified by environmental conditions such as the presence of lipoproteins.

Alkaloids↗
PubMed1993

The immunomodulating agent RU 41740 complexed with very-low-density lipoproteins enhances human polymorphonuclear neutrophil oxidative metabolism in vitro.

Added to human serum in vitro, RU 41740, an immunomodulating agent extracted from Klebsiella pneumoniae, binds selectively to lipoproteins containing apolipoprotein B (low-density lipoproteins and very-low-density lipoproteins, VLDL) and, at higher concentrations, to lipoproteins containing apolipoprotein A (high-density lipoproteins). The fact that lipoproteins modulate polymorphonuclear neutrophil (PMN) functions led us to suspect that the VLDL-RU 41740 complex might affect PMN functions. In this study, the effect of this complex on PMN superoxide generation was measured in the presence and absence of the classical stimulants formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate. The VLDL-RU 41740 complex enhanced the stimulating effect of VLDL on quiescent PMN, but not following stimulation with formyl-methionyl-leucyl-phenylalanine. In contrast, it partially counteracted the inhibiting effect exerted by VLDL alone on phorbol myristate acetate stimulation. Such a complex might be formed in vivo during RU 41740 therapy and constitute an important feature in the immunostimulating properties of the drug.

Adjuvants, Immunologic↗
PubMed1993

Lipid peroxidation abnormalities in hemodialyzed patients.

In order to test the existence of a possible oxidative damage during hemodialysis, plasma conjugated dienes (CD), plasma and red blood cell (RBC) thiobarbituric acid (TBA) reactants were investigated in 25 patients receiving regular dialysis treatment (RDT). The RBC TBA reactant concentration was significantly increased in RDT patients in comparison with healthy subjects. The extracellular antioxidant systems were evaluated by the assay of plasma antioxidant activity, plasma tocopherol, urate, transferrin, haptoglobin and ceruloplasmin levels. Except urate and transferrin, none of these parameters were different between the two groups. On the other hand, in RDT patients, RBC superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were significantly lower than in healthy subjects. There was an inverse correlation between decreased RBC GPX and RBC TBA reactant concentration. These results show in RDT patients the existence of an oxidizing stress, mainly intracellular, which could be due, in part, to a decrease in SOD and GPX activities.

Adolescent↗
PubMed1993

Serum and urinary alpha-1 acid glycoprotein in chronic renal failure.

The concentration and concanavalin A (ConA)-dependent microheterogeneity of serum and urinary alpha 1-acid glycoprotein (AGP) were studied in patients with various degrees of renal impairment and compared with healthy control values. Serum concentrations of AGP were significantly higher in hemodialyzed and uremic patients than in the control subjects (1.54 +/- 0.42 g/l, p < 0.05, and 1.20 +/- 0.40 g/l, p < 0.05, respectively, versus 0.83 +/- 0.17 g/l). There was a similar increase in serum alpha 1-protease inhibitor and haptoglobin concentrations in the uremic patients (r = 0.87 and r = 0.70; p < 0.001). Urinary concentrations of AGP were also significantly higher in the hemodialyzed and uremic patients than in the control subjects, despite wide variability in the patients (20 +/- 14 mg/24 h, p < 0.05, and 126 +/- 160 mg/24 h, p < 0.05, respectively, versus 3 +/- 1 mg/24 h). AGP clearance was significantly higher in the uremic patients than in the hemodialyzed patients (p < 0.01) and the control subjects (p < 0.01). The proportions of strongly ConA-reactive AGP fractions were higher in the serum of the hemodialyzed (18.6 +/- 5.2%; p < 0.05) and uremic patients (18.1 +/- 5.3%; p < 0.05) than in the control subjects (14.5 +/- 2.5%). There was a similar difference in the urine samples (26.7 +/- 8.2%, p < 0.01; 20.1 +/- 6.2%, p < 0.01, respectively, versus 10.3 +/- 4.8%), with also a significant difference between the hemodialyzed and uremic patients (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗
PubMed1992

Evaluation of intestinal clearance and faecal excretion of alpha 1-antiproteinase and immunoglobulins during Crohn's disease and ulcerative colitis.

The intestinal clearance of alpha 1-antiproteinase, monomeric IgA and IgG, and the daily fecal output of polymeric IgA and IgM were investigated in patients with inflammatory bowel diseases (inactive and active Crohn's disease, ulcerative colitis) and in a control group. The intestinal clearance of alpha 1-antiproteinase was significantly increased in all patients with inflammatory bowel diseases (p less than 0.01), irrespective of the grade of the disease. In contrast, increases in intestinal clearances of monomeric IgA and IgG were more closely related to the severity of the intestinal lesions. The associate determination of these three quantities should therefore be of interest for monitoring the degree of intestinal bowel inflammation. Faecal output of polymeric IgA was significantly increased in active intestinal disease (p less than 0.01), whereas faecal IgM levels were not. The determination of the faecal output of polymeric IgA should contribute to the assessment of the activity of inflammatory bowel diseases, and may provide insight into the activation of the mucosal immune system.

Adolescent↗
PubMed1991

In vitro modulating effect of human very-low-density lipoproteins on human polymorphonuclear leukocyte oxidative metabolism and migration.

In this work, the in vitro effects of very-low-density lipoproteins (VLDL) on human polymorphonuclear leukocyte (PMN) oxidative metabolism and migration were studied. VLDL stimulated PMN superoxide generation in absence of other stimulating agents. The effect of VLDL from normotriglyceridemic subjects was more marked than with VLDL from hypertriglyceridemic subjects. VLDL reduced in a dose-dependent manner the luminol-dependent chemiluminescence of PMN stimulated by phorbol myristate acetate (PMA) and, to a lesser degree, by opsonized zymosan. This effect was observed with VLDL concentrations found in healthy and hypertriglyceridemic patients. Superoxide anion generation was also reduced by preincubation of PMN with VLDL before stimulation with PMA but not opsonized zymosan. VLDL were not cytotoxic for PMN. The above effects appear to be an intrinsic property of VLDL and might lead to reduced PMN-mediated non-specific host defences in hypertriglyceridemic subjects.

Cell Movement↗
PubMed1991

Effect of an immunomodulating agent, RU 414740, on polymorphonuclear responsiveness after burn injury.

An impairment of polymorphonuclear leukocyte (PMN) functions has been described following burn trauma. It was thus of interest to investigate the effect of RU 41740, an agent known to stimulate these cells, on rat PMN functions after burn injury. In the present study the responsiveness to classical stimuli of PMN from untreated burned rats was approximately 40% lower than healthy control values. In vitro treatment with RU 41740 increased oxidative metabolism of PMNs from burned and healthy rats. The effect was dose-related but was most striking in the case of PMNs from healthy rats. Significant differences were obtained with concentrations higher than 1 micrograms/ml for healthy rats but only 10 micrograms/ml for burned rats. In vivo treatment with RU 41740 also led to an enhancement of PMN oxidative metabolism on both burned and healthy rats. The maximal effective dose was 10 mg/kg/day in both cases. In contrast, 25 and 50 mg/kg/day doses inhibited PMN oxidative metabolism.

Adjuvants, Immunologic↗
PubMed1991

Role of cytoskeleton and surface lectins in Giardia duodenalis attachment to Caco2 cells.

An in vitro model of Giardia duodenalis and the Caco2 cell line enable the study of parameters that could play a part in trophozoite attachment. We explored the role of membranous lectins of G. duodenalis in attachment-inhibition studies using carbohydrates in solution. Attachment rates were reduced by 14% and 23% in the presence of 100 mmol/l mannose-6-phosphate and glucose, respectively, as compared with control values. No significant modification was observed after trophozoite trypsinization at room temperature or at 37 degrees C. The inhibitory effects of colchicine (35%) and nocodazole (70%) suggest a primordial role of the cytoskeleton; microtubules appear to be the principal effectors of trophozoite fixation. Scanning electron microscopy revealed circular imprints on the Caco2 brush border after trophozoite detachment. The mechanisms of attachment of G. duodenalis to intestinal enterocyte-like cells in culture are thus essentially of the mechanical or hydrodynamic type; surface lectins would appear to intervene in the specificity for duodenal cells.

Animals↗
PubMed1991

Influence of uremia on polymorphonuclear leukocytes oxidative metabolism in end-stage renal disease and dialyzed patients.

The oxygen (O2) consumption, and superoxide anion (O2-.) and hydrogen peroxide (H2O2) production by polymorphonuclear leukocytes (PMNs) were investigated in 5 end-stage renal disease patients, before and after the 1st, 4th and 10th dialysis sessions. Resting values of O2-. production and O2 consumption were not significantly different from values for PMNs from normal subjects. After stimulation by opsonized zymosan or phorbol myristate acetate, the three parameters measured were significantly (p less than 0.001) enhanced in comparison with healthy control values. Cross-incubation studies showed a lack of effect of patient plasma on O2-. production by stimulated control cells: PMN oxidative metabolism would therefore appear to be increased in these patients. The anomalies observed probably arise via a mechanism involving a cellular dysfunction resulting from the renal disease, rather than from the presence of a plasma factor.

Adult↗
PubMed1991

[Membrane phospholipid peroxidation in renal insufficiency and chronic hemodialysis].

Lipid peroxidation is a result of the fatty acid side-chains of cellular membrane phospholipids attack by oxygen-derived free radicals. It has been suggested that some of the complications related to haemodialysis may be due to ineffective antioxidant systems and/or an increased free oxygen radical production. Serum antioxidant activity in patients undergoing regular dialysis treatment has been shown to be significantly decreased and to exhibit high malondialdehyde levels indicating that the patients were susceptible to cellular injury by lipid peroxidation. Superoxide dismutase and glutathion peroxidase activities are decreased in plasma and erythrocytes. Moreover, in uremia, blood cell and mononuclear cell membranes contents of vitamin E are reduced. Thus, chronic uremic patients seem to have defective plasma and cellular antioxidant mechanisms together with an increase of circulating free radical reaction products.

Antioxidants↗
PubMed1991

Serum alpha-1 acid glycoprotein in chronic renal failure and hemodialysis.

The total concentration and concanavalin A (ConA)-dependent microheterogeneity of alpha-1 acid glycoprotein (AAG) were studied in thirty hemodialyzed uremic patients and eighteen non-dialyzed uremic patients, by comparison with healthy volunteers. Serum concentrations of AAG were significantly higher in the non-dialyzed uremic (1.27 +/- 0.47 g/l) and hemodialyzed patients (1.29 +/- 0.33 g/l) than in the volunteers (0.79 +/- 0.09 g/l). The proportions of strongly ConA-reactive AAG fractions were also higher in non-dialyzed uremic (16.7%) and hemodialyzed patients (18.5%) than in volunteers (14.1%). These data may be related to an increase in bi-antennary glycans, as observed in patients on peritoneal dialysis, together with a probable change in sialylation. AAG serum levels and microheterogeneity were similar in non-dialyzed and hemodialyzed patients and did not appear in the dialyzed patients to depend on the type of dialysis membrane used, i.e. cuprophan (CU), cellulose acetate (CA), hemophan (HE), polyacrylonitrile (PAN), and polysulfon (PS), in spite of differences in biocompatibility. In patients dialyzed with CA membranes, there was a distinct decrease in the ConA non-reactive fraction (38.0%) and an increase in ConA slightly-reactive (42.2%) and strongly-reactive (19.7%) fractions. Differences in AAG serum levels and ConA reactivity between patients dialyzed with CA and PAN membranes seem to justify further investigations of other acute-phase reactants and immunological parameters.

Concanavalin A↗
PubMed1990

Characterisation of the main molecular forms of human fecal immunoglobulin A.

The molecular composition of fecal IgA is poorly documented, although it is of theoretical and practical importance to determine the different forms of IgA in faeces. Two main molecular forms were isolated by successive steps of ion-exchange chromatography and gel-filtration. The first consisted of secretory IgA dimers dissociating into slightly lower molecular mass forms under the influence of the electric field during electrophoresis. The other contained cleaved-IgA complexed with alpha 1-antitrypsin, that is considered to be a serum origin marker. These results confirm that secretory IgA are relatively resistant to digestive enzymes in vivo, and suggest that alpha 1-antitrypsin-bound fragments originate from serum IgA monomers. Analysis of the proportions of these forms may be of value in the investigation of gut diseases.

Chromatography, Gel↗