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Biomedical subjects

D Raichvarg

Publications and source records attributed to D Raichvarg.

At least 37 records · Page 2Linked to original sources

Modulation of human polymorphonuclear neutrophil functions by alpha 1-acid glycoprotein.

alpha 1-Acid glycoprotein (alpha 1-AGP), a naturally occurring human plasma protein and acute-phase reactant, was extracted by a two-step procedure from sera collected from four healthy men. Its activity was tested in vitro on human polymorphonuclear (PMN) functions (migration, aggregation, O2- generation). alpha 1-AGP was not chemoattractant but inhibited the PMN response to the chemoattractant formylmethionyl-leucyl-phenylalanine without affecting spontaneous migration (Boyden and agarose methods of assessment). At concentrations between 0.15 and 0.45 mg/ml, alpha 1-AGP exerted an aggregating effect with a maximal effective concentration of 0.3 mg/ml. alpha 1-AGP inhibited superoxide generation by PMNs stimulated either by opsonized zymosan or phorbol myristate acetate. This inhibition varied according to the intensity of the stimulation. At low stimulus concentrations, a dose-dependent inhibition of membrane-associated PMN responsiveness to soluble or particulate stimuli was observed. These findings suggest that alpha 1-AGP may be able to prevent PMN activation in the course of inflammatory processes in vivo.

Cell Aggregation↗

Adherence and multiplication of Giardia intestinalis on human enterocyte-like differentiated cells in vitro.

This report describes a technique for studying the adherence and growth of Giardia intestinalis trophozoites (strains PARIS/86/LCF/1, PARIS/86/LCF/2 and PARIS/88/LCF/8) using the human colon carcinoma cell line Caco2. Giardia trophozoites were cultured with Caco2 cells in a modified HSP3 culture medium. The biochemical differentiation of Caco2 cells was established by an increase in sucrase isomaltase activities to values of 4.51 +/- 0.90 and 10.39 +/- 3.00 milliunits/mg protein for 8- and 12-day-old cultures, respectively. Giardia, adherence to 8- and 12-day-old Caco2 cells reached a value of greater than 75% after 60 and 30 min, respectively. Adherence diminished significantly at 24 degrees C and was almost undetectable at 4 degrees C. Depletion of divalent cations reduced the proportion of adherent trophozoites by up to 46%. Adherence was pH-independent between pH 6.0 and 7.6. Parasite growth increased when Caco2 cell monolayers were used instead of axenic cultures. This in vitro human cell model may contribute to the study of the mechanisms and factors involved in the host-parasite interaction.

Animals↗

[Metabolism and septic shock].

Despite continuous monitoring progress, septic shock remains the main cause of death in Intensive Care Units. Septic stress triggers a complex array of biological modifications resulting in an acquired disease of intermediary metabolism whose main characteristic is an inefficient cellular use of glucidic, lipidic and protidic substrates together with oxygen. The purpose of this review is to present metabolic disturbances observed during sepsis and septic shock.

Bacterial Infections↗

[Inhibitory action of tiopronin on free radicals].

Free oxygen radicals are involved in many pathological conditions and particularly in the inflammation which characterizes rheumatic disorders. Tiopronin (Acadione), a new basic treatment for rheumatoid arthritis, and sodium 3-aurothio-2-hydroxypropane-1-sulfonate (Allochrysine), the reference treatment for the disease, have been tested in vitro for their ability to regulate the free radicals produced by inflammatory murine macrophages or granulocytes. The production of free radicals was measured using the technique of luminol-dependent chemoluminescence. Results show that tiopronin causes dose-dependent inhibition of chemoluminescence whereas, under the same experimental conditions, sodium 3-aurothio-2-hydroxypropane-1-sulfonate leads to a stimulation in production of the radicals. Taking into consideration the deleterious effects of free radicals in rheumatic disorders, inhibition of the radicals may be considered as forming part of tiopronin's mode of action.

Acetylcysteine↗

Comparative effects of F1 and P1 fractions obtained from a Klebsiella pneumoniae glycoproteic extract (RU 41740) on polymorphonuclear leukocytes.

RU 41740 is a glycoprotein extract from Klebsiella pneumoniae described as a macromolecular aggregation of a lipopolysaccharide (LPS)-associated protein (F1 fraction) and a glycoproteic complex (P1 fraction). The human polymorphonuclear (PMN) response was studied after incubation of the cells in the presence of RU 41740, F1 and P1 fractions, or F1-P1 complex. Oxidative metabolism was assessed by chemiluminescence, O2 consumption, O2- generation, and degranulation by beta-glucuronidase release. Results were compared to data obtained with a homologous LPS. RU 41740, F1 fraction, and F1-P1 complex increased the respiratory burst of PMNs stimulated by opsonized zymosan (OZ). N-formylmethionylleucylphenylalanine (fMLP), phorbol myristate acetate, or the calcium ionophore A23187. The beta-glucuronidase release was stimulated by the same compounds when OZ or fMLP were used as stimuli. These effects were dose-dependent. In contrast, P1 fraction was inactive. Addition of polymyxin B resulted in a profound inhibition of both the F1 fraction and LPS activities but only in a partial inhibition of RU 41740 effects. These results strengthen the hypothesis that different biochemical pathways are involved in the enhancement of stimulated neutrophil functions by RU 41740.

Adjuvants, Immunologic↗

In vitro and in vivo effects produced by the immunomodulating agent RU 41740 on human polymorphonuclear leukocytes in the elderly.

The activity of RU 41740, a glycoprotein extract from Klebsiella pneumoniae has been investigated on some polymorphonuclear (PMN) functions. Chemotaxis, random migration and oxidative metabolism (assessed by chemiluminescence, O2 consumption and O2- generation) were studied in parallel. PMN were collected from adult and aged human volunteers. Experiments were performed either in vitro or in vivo in a double blind placebo assay. In both PMN populations RU 41740 enhanced oxidative metabolism either in in vivo or in vitro experiments. However, a higher and dose-related activity was observed on PMN collected from the younger subjects whereas maximal effective concentration was reached earlier with PMN collected from aged subjects. RU 41740 did not modify random migration but inhibited chemotaxis of PMN collected from the younger population in a dose-related manner. These data corroborated previous results observed on PMN collected from various animal species and suggested an interaction of RU 41740 on PMN membrane. Moreover drug-induced macrophage and lymphocyte stimulation might also explain, at least in part, the in vivo effects described in this study. Thus RU 41740 could partly account for the protective effects exerted against bacterial and fungal infections through its activity on PMN functions.

Adult↗

Influence of the surface area of different dialysis membranes on granulocyte adherence and superoxide generation.

Granulocyte adherence and superoxide anion generation were investigated in vitro in the presence of dialysis membrane fragments incubated with normal human polymorphonuclear cells. Dialysis membranes made from cellulosic material or non-cellulosic material like polyacrylonitrile, polymethylmetacrylate, and polysulfone were tested. The membrane surface area varied (1-5 cm2) while the membrane surface/polymorphonuclear cells ratio was maintained constant (2 X 10(6) cells/cm2). The contact of polymorphonuclear cells with increasing membrane surface area generated a significant decrease of superoxide anion generation (5-80% of inhibition) and produced an increase of granulocyte adherence (5-52%). This phenomenon was observed for all the tested membranes, whether opsonized zymosan or phorbol myristate acetate were used as stimuli. Similar results were obtained after washing the dialysis membrane or when polymorphonuclear cells were suspended in homologous serum. In vitro exposure of granulocytes to cellulosic or non-cellulosic dialysis membranes caused a surface-area dependent modification of polymorphonuclear functions.

Cell Adhesion↗

Characterization and identification of substances isolated from dialyzer extracts.

The organic phase of dialyzer dried extracts obtained from Cuprophan hollow fiber and polyacrylonitrile AN 69 parallel-plate dialyzers, all sterilized by ethylene oxide, were submitted to light and polarized light microscopy, infrared (IR) spectrophotometry, and gas chromatography coupled with mass spectrometry. Colorless polygonal (approximately 5 X 20 micron) and needle-like (approximately 3 X 50 micron) crystals were found in great quantity on microscopy examination. IR spectrophotometry of the crystals embedded in potassium bromide disc showed specific spectra in the 1400-800 cm-1 wave number range and typical peaks on wave number assigned for hydroxy or amine (3420 cm-1), aromatic hydrogen (3060 cm-1), methyl, methylenic, or methenyl (2960-2860 cm-1), and carbonyl (1715 cm-1) groups can be demonstrated. Seven peaks were detected on gas chromatography of the organic solution containing crystals. Fatty acids and undefined compounds could originate from the dialyzer. Phtalates may leach from blood tubing, used in the rinsing procedure, and BHT is a stabilizer of ethyl ether used as solvent. These compounds could also originate from the dialyzer since phtalates are widely used as a plasticizer and BHT an antioxidant for various polymers.

Acrylic Resins↗

Individual free fatty acids and lactate uptake in the human heart during severe sepsis.

Coronary haemodynamics and myocardial metabolism of nonesterified fatty acids (NEFA) and lactate were studied in 11 patients with severe sepsis, and compared to 10 control subjects. Coronary sinus blood flow was evaluated by thermodilution. Arterial and coronary sinus blood samples were collected for the measurement of lactate and total and individual NEFA concentrations both in septic and control patients. There was an increase in lactate and total NEFA arterial concentrations with a marked increase in palmitic and linolenic acids. The uptake of the main NEFA (C14:0 to C18:2) was significantly decreased. In the control group, individual NEFA uptake was proportional to their arterial concentrations. This relationship was not observed in patients with sepsis: there was no preferential extraction of any particular NEFA. Furthermore, in patients with sepsis, myocardial oxygen consumption did not correlate with NEFA, but only with lactate uptake. Alterations in NEFA uptake were found to be constant during severe sepsis and are consistent with major disturbances in myocardial metabolism.

Coronary Circulation↗

Modulation by RU 41740 of oxidative metabolism and migration of rat polymorphonuclear leukocytes collected after induction of immune and nonimmune inflammations.

The activity of an immunomodulating agent, RU 41740, on the behavior of polymorphonuclear leukocytes (PMNs) elicited by two models of inflammation was studied. We observed the effect produced on migration and oxidative metabolism after incubation in vitro, in various drug concentrations, or administration in vivo. A stimulation of oxidative metabolism and an inhibition of chemotaxis was observed with the two types of PMNs. However Arthus-elicited PMNs were less reactive. This might be related to a nonspecific deactivation of the cells after induction of such an immune inflammatory reaction. This evidenced that PMN reactivity greatly varies with the physiopathological state of the cells.

Animals↗

Effects exerted by RU 41740 on oxidative metabolism and migration of rat polymorphonuclear leukocytes collected after induction of one acute non specific inflammatory reaction.

The activity of RU 41740, a glycoprotein extract from Klebsiella pneumoniae, endowed with immuno-modulating properties, has been investigated on polymorphonuclear (PMN) leukocyte functions. This report deals with the effect of RU 41740 on oxidative metabolism (assessed by chemiluminescence, 02 consumption and O2- production) and on chemotaxis and random migration (using agarose and Boyden chamber techniques). PMNs were collected from the rat pleural cavity after induction of one acute inflammatory reaction (pleurisy induced by injection of a suspension of calcium pyrophosphate crystals). Experiments were performed in parallel after in vivo treatment or incubation in vitro. RU 41740 enhanced PMN oxidative metabolism and inhibited PMN chemotaxis while random migration was only affected using agarose assay at high concentration. This effect on PMN migration was observed with at least two attractants. These observations have been obtained either after incubation in vitro or administration in vivo. The minimal effective dose was 1 mg/kg in vivo and 0.1 microgram/ml in vitro. These data suggest that RU 41740 acts directly on PMN membrane receptors.

Animals↗

Effects of storage on the pyruvate-lactate system and random migration of human granulocytes.

This work demonstrates a time-dependent loss of polymorphonuclear neutrophilic leukocyte (PMN) functions during the first 48 h with only slight lysis and release of cellular LDH. It confirms that storage decreases ATP levels in PMNs and significantly increases intracellular lactate and pyruvate. These data correlated with an inhibition of PMN migratory function and a considerable decrease in chemiluminescence response.

Adenosine Triphosphate↗

Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock.

To investigate disturbances in the coronary circulation and myocardial metabolism during septic shock, we examined coronary sinus blood flow and myocardial substrate extraction in 40 patients with septic shock and 13 control patients. Patients with coronary artery disease were excluded from this study. The global hemodynamic pattern of the septic patients was characterized by a lower stroke volume, despite an elevated cardiac index. Coronary sinus blood flow was high (187 +/- 47 vs 130 +/- 21 ml/min in the control group, p less than .001) due to marked coronary vasodilation, especially in the subgroup of nonsurvivors. In contrast to the control group, myocardial lactate uptake was elevated, while that of free fatty acids, glucose, and ketone bodies was diminished in patients with septic shock. These findings were especially prominent in the nonsurvivors. Expressed as oxygen equivalents, the contribution of free fatty acids as an energy source of the myocardium was markedly diminished in septic patients (12% vs 54% in the control group, p less than .005), while that of lactate was increased (36% vs 12%, p less than .01). The observed shift in myocardial substrate extraction was associated with a discrepancy between measured myocardial oxygen consumption and that calculated chemically from commonly available exogenous substrates: 41% of myocardial oxygen consumption was not explained by the utilization of commonly available substrates extracted from coronary circulation in all patients with septic shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Measurement of total, monomeric and polymeric IgA in human faeces by electroimmunodiffusion.

Total (t), monomeric (m) and polymeric (p) immunoglobulin A (IgA) levels were simultaneously measured in mixed faecal material collected over three consecutive days using a modified one-dimensional immunoelectrophoretic assay, which is a precise and reproducible method. Faecal t-, m- and p-IgA levels were statistically higher in 32 diarrhoeic patients than in a group of 16 healthy subjects (respectively 2.2, 2.6 and 2.0 times the normal). The values were also significantly different (P less than 0.001) when results were expressed as output per day in order to estimate the secreting capacity of gut. Moreover, the m-IgA/t-IgA percentages were significantly higher in faeces from diarrhoeic patients (42.3%) than in normal faeces (26.5%). These results confirm the importance of faecal IgA determination in estimating the local production of the IgA in various gastrointestinal tract disorders.

Adult↗

[Functions and metabolism of polynuclear neutrophils in patients under chronic hemodialysis].

Clinical evidence indicates that infection is still a cause of morbidity and mortality in patients undergoing hemodialysis. The major role played by the polymorphonuclear cells in antimicrobial response by the host explained considerable study of several aspects of granulocyte functions in chronic hemodialysis patients. It is now well documented that hemodialysis induces the sequential activation of the complement components of the alternative pathway and may provide a mechanism for initiating leukoaggregation and sequestration of granulocytes. This complement activation could also explain the profound leukopenia observed shortly after the initiation of hemodialysis. It has been also assumed that the sequestration of granulocytes is dependent on a temporarily altered cell function and leads to a depressed chemotaxis, an impairment of phagocytic and bactericidal capacities. Moreover, a significant defect in the oxidative metabolism was observed before and during the course of the dialysis session. This article summarizes research that has been done on the function of neutrophils from chronic hemodialysis patients.

Blood Bactericidal Activity↗