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L Baud

Publications and source records attributed to L Baud.

At least 91 records · Page 5Linked to original sources
PubMed1986

[Detection of drug-induced nephrotoxicity].

This is a report of a round table organized during the second meeting of Clinical Pharmacology held in Giens (France) in September 1985. At the beginning of the meeting, the clinical aspects of drug-induced nephrotoxicity were reviewed. Thus we tried to precise the real interest of the studies of proteinuria, urinary cytology, enzymuria and fractional clearances of lithium or magnesium. The most interesting part of our discussions was to know the point of view of men working in drugs companies when a renal abnormality is found during a clinical trial of a drug and when previous experimental studies did not find any renal adverse effects of the drug. It was suggested in a such situation to do particular studies. Methods generally used to study renal physiology as autoradiography micropuncture, microinjection had to be performed to localize the action of the drug along the nephron. It was also discussed of the use of isolated perfused kidney as a tool in drug disposition and the use of renal cells culture. A better understanding of the mechanisms of direct renal toxicity of drugs was obtained from the results of experimental models. It is not so easy, at the present time, to know the mechanisms of immunological drug-induced nephrotoxicity. It seems necessary to develop new experimental models. The results obtained in animals with Cl2Hg or D. Penicillamine or gold salts afford to suspect some mechanisms for these types of nephropathies. This aspect of drug induced nephropathy is more complex because there is a large interindividual variation in susceptibility to these drugs.

Animals↗
PubMed1985

Lipoxygenase products mediate the attachment of rat macrophages to glomeruli in vitro.

Because there is an accumulation of macrophages in the Bowman's space during human and experimental glomerulonephritis, we have studied the binding of [3H]-uridine labeled macrophages to isolated glomeruli. Binding was related to the glomerular protein and macrophage concentrations, temperature, time of incubation, and was a saturable process. Macrophage adherence depended on glomerular lipoxygenase activity but not on glomerular cyclooxygenase activity since preincubation of glomeruli with nordihydroguaiaretic acid (NDGA) inhibited this phenomenon whereas preincubation with indomethacin was ineffective. Glomeruli interacted with macrophages in converting arachidonic acid (C20:4) to prostaglandins (PG) since productions of 6 keto-PGF1 alpha, TXB2, and PGD2 by glomeruli and macrophages incubated in combination were much greater than the sums of their respective productions by glomeruli and macrophages incubated separately. Macrophages were the source of the supplementary synthesis of PG which was abolished when these cells were pretreated with aspirin. Stimulation of macrophages by glomeruli was blunted by pretreatment of glomeruli with NDGA. Production of PG and of 12-HETE by macrophages was stimulated by a lipid extract of glomeruli containing the oxygenated metabolites of C20:4. Direct addition of 12-HPETE also stimulated macrophage functions. These data suggest that macrophage attachment to glomeruli and macrophage stimulation in the presence of glomeruli depend on glomerular lipoxygenase activity.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1985

Leukotriene C4 binds to human glomerular epithelial cells and promotes their proliferation in vitro.

In human and experimental glomerulonephritis, glomerular hypercellularity results both from accumulation of macrophages and proliferation of resident glomerular cells. The recent identification of macrophage-derived factors that stimulate mesangial and epithelial cell proliferation suggests that these factors might contribute to the hypercellularity. To determine the identity of such macrophage-derived growth factors, we studied the effect of leukotrienes (LTs), products that are released from macrophages and leukocytes, on proliferation of human glomerular epithelial cells in culture. Dose-dependent (1-100 nM) stimulation of [3H]thymidine incorporation, an index of cell proliferation, was observed in cells incubated with the sulfidopeptide LTs, LTC4 and LTD4, but not with LTB4. The response was 248 and 172% of control values at 100 nM LTC4 and LTD4, respectively. This effect of LTC4 was abolished by FPL 55712. Subsequent binding studies demonstrated that glomerular epithelial cells possess specific receptors for LTC4. [3H]LTC4 bound rapidly at 8 degrees C to the cells. There was a plateau after 40 min incubation. Maximum specific binding was 70-90% of total binding. Specific binding was totally reversible with addition of an excess of unlabeled LTC4. Analysis of time-course association slopes at two concentrations of [3H]LTC4 and of the competition between a single concentration of [3H]LTC4 and increasing concentrations of unlabelled LTC4 allowed calculation of dissociation constants (Kd) of 220 and 217 nM, respectively. Both LTD4 and LTE4 exhibited ED50 values that were at least one order of magnitude higher than for LTC4. Thus, our findings suggest that LTC4 binds to specific receptors of glomerular epithelial cells, promotes proliferation of these cells, and could contribute to epithelial hypercellularity found in glomerulonephritis.

Cell Division↗
PubMed1984

Glomeruli cooperate with macrophages in converting arachidonic acid to prostaglandins and hydroxyeicosatetraenoic acids.

The interaction of proliferating macrophages with the glomerulus may play an important role in certain forms of glomerulonephritis. This interaction could involve metabolites of arachidonic acid (C20:4) such as prostaglandins (PG) and lipoxygenase products. We therefore investigated the conversion of exogenous [3H] C20:4 into hydroxyeicosatetraenoic acids (HETE) and PG by isolated glomeruli and macrophages from rats, alone and in combination. As demonstrated by HPLC, glomeruli converted C20:4 predominantly to lipoxygenase products -mainly 12-HETE- and, to a lesser extent, to PG. Resident macrophages converted C20:4 to equivalent amounts of HETE and PG, mainly 12-HETE and 6 keto-PGF1 alpha. When macrophages and glomeruli were studied in combination, a striking interaction was detected in both pathways of C20:4 metabolism. Production of 6 keto-PGF1 alpha was stimulated and considerable amounts of TXB2, PGD2 and hydroxyheptadecatrienoic acid (HHT) were also produced. Total 12-HETE production was unchanged. When a lipid extract of glomeruli, containing oxygenated metabolites of C20:4, was added to macrophages, stimulation of 12-HETE occurred without any change in HHT or PG formation. When, on the contrary, a lipid extract from macrophages was added to glomeruli, 12-HETE production by the glomeruli was nearly completely abolished. Thus the unchanged total 12-HETE production by coincubated glomeruli and macrophages resulted from its increased production by macrophages and its decreased production by glomeruli. These data suggest that interaction between glomeruli and macrophages results in activation of C20:4 metabolism by macrophages followed by inhibition of C20:4 metabolism by glomeruli. Such a regulatory process could play a role in the inflammatory response to immunological injuries during macrophage-dependent human and experimental glomerulonephritis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1984

Effect of platelet-activating factor and serum-treated zymosan on prostaglandin E2 synthesis, arachidonic acid release, and contraction of cultured rat mesangial cells.

The interaction of inflammatory cells and glomerular prostaglandins (PG) may be important during glomerulonephritis. We therefore examined the influence of platelet-activating factor (PAF), (a mediator of inflammation released from leukocytes) and of phagocytosis of zymosan on arachidonic acid metabolism and on cell contractility in rat glomerular mesangial cells in culture. PAF increased PGE2 synthesis (determined by radioimmunoassay) within minutes (threshold: 10(-10)M; maximal effect: 10(-7)M). Serum-treated zymosan also stimulated PGE2, but with a slower onset. In cells prelabeled with [14C]arachidonic acid both PAF and serum-treated zymosan released 14C from phospholipids and increased free [14C]arachidonate. The ratio of 14C-release to PGE2 was, however, different with PAF and serum-treated zymosan, indicating different phospholipid pools. Under phase-contrast microscopy, PAF caused contraction of mesangial cells with a dose-response and time-course parallel to that for PGE2 synthesis. Serum-treated zymosan caused no contraction. The PAF-induced contraction was enhanced by PG synthesis inhibition and was attenuated by addition of PGE2, indicating a feedback mechanism. The mesangial contraction by PAF may be important in favoring deposition of immune complexes, while the PGE2 synthesis stimulated by PAF and by phagocytosis of zymosan may counteract the deleterious effects of PAF during induction of glomerulonephritis.

Animals↗
PubMed1983

Reactive oxygen production by cultured rat glomerular mesangial cells during phagocytosis is associated with stimulation of lipoxygenase activity.

To investigate the phagocytic capability of glomerular mesangial cells and the biochemical events associated with phagocytosis, rat cultured mesangial cells were incubated in the presence of opsonized zymosan (STZ) and production of reactive-oxygen species and lipoxygenase products were determined. Mesangial cells were identified on the basis of morphologic (presence of microfilaments and pattern of staining by an anti-myosin antiserum) and physiologic (contractile activity in response to angiotensin II) characteristics. No contamination by esterase-positive cells was observed. Electron microscopy revealed that the phagocytic process started after 5 min of incubation, and affected approximately 50% of the cells. Superoxide anion (.O2-) and hydrogen peroxide (H2O2) generation by mesangial cells exposed to STZ increased with time and STZ concentration. Cells incubated with zymosan particles treated with heated serum produced undetectable amounts of .O2- and 6 times less H2O2 than cells exposed to STZ. Pretreatment by cytochalasin B produced a marked decrease in STZ-stimulated production of reactive oxygen species. [3H]Arachidonic acid was incorporated into mesangial cell phospholipids and its release and conversion into monohydroxyeicosatetraenoic acids (HETE) was measured by radiometric high performance liquid chromatography (HPLC). Incubation with STZ markedly stimulated the release of arachidonic acid from its phospholipid stores and its transformation into 11-, 12-, and 15-HETE. Lipoxygenase inhibitors inhibited STZ-stimulated H2O2 production, whereas they did not modify the phagocytic process as shown by the absence of any effect on the uptake of 125I-STZ by the mesangial cells. This study demonstrates that a high percentage of rat cultured mesangial cells phagocytose opsonized particles. The phagocytic process results in an oxidative burst that appears to be dependent on stimulation of the lipoxygenase pathway.

Animals↗
PubMed1982

[Protective effect of procyanidolic oligomers on the heterologous phase of glomerulonephritis induced by anti-glomerular basement membrane antibodies].

Treatment by procyanidolic oligomers can significantly decrease the proteinuria indiced in the Rat by intravenous injection of anti glomerular basement membranes antibodies. Immunohistological analysis shows that procyanidolic oligomers do not interfere with the mechanisms of immunopathological injury involved in this model (antibody binding to glomerular basement membrane, complement activation, glomerular influx of polymorphonuclear leucocytes). Their protective effect may be due to an increased resistance of the glomerular capillary to the inflammatory mediators released by neutrophils.

Animals↗
PubMed1982

Stimulation of PGE2 synthesis by mercuric chloride in rat glomeruli and glomerular cells in vitro.

PGE2 production in the presence of mercuric chloride was measured by specific radioimmunoassay in isolated whole glomeruli and in cultured glomerular cells. Under basal conditions, mercuric chloride at 10 micrograms.ml-1 caused a twofold stimulation of PGE2 in isolated whole glomeruli, and at 1 to 10 micrograms.ml-1 it caused a more marked increase of PGE2 (eight times the control value) in mesangial or epithelial glomerular cells. An excess of arachidonic acid, however, blunted the stimulatory effects of mercury. Furthermore, the effect of mercuric chloride on PGE2 production was only observed with intact preparations but not with cell homogenates. Mercury inhibited cyclooxygenase activity in purified glomerular microsomes. It also inhibited phospholipase activity in purified glomerular cell membranes, whereas it stimulated phospholipase activity in intact cells. These results demonstrate that mercury modifies PGE2 synthesis via multiple mechanisms. Stimulation occurring at low doses of mercury can be attributed to the indirect activation of phospholipase. We suggest that mercuric chloride suppresses the inhibitory effect of lipomodulin on this enzyme.

Animals↗
PubMed1981

Stimulation by oxygen radicals of prostaglandin production by rat renal glomeruli.

Polymorphonuclear leukocytes secreting oxygen radicals are found in the glomerular capillaries at an early stage of experimental acute glomerulonephritis. The aim of this work was to study the effects of these radicals on prostaglandin (PG) production by the glomeruli. Glomeruli were isolated from rat renal cortex and incubated in the presence of a biochemical system capable of generating oxygen radicals (addition to 100 microM xanthine of increasing concentrations of xanthine oxidase). Synthesis of PGE2, PGF2alpha, 6 keto PGF1alpha, and TXB2 estimated using specific radioimmunoassays was twofold greater in the presence of oxygen radicals. This effect was inhibited by catalase, slightly stimulated by superoxide dismutase, unaffected by hydroxyl radical scavengers, thus suggesting that hydrogen peroxide was the by-product responsible. This was confirmed by the stimulatory effect of hydrogen peroxide itself (1 to 100 microM) on PG synthesis. The effect of mepacrine, an inhibitor of phospholipase activity, on PG production was more marked in the presence of hydrogen peroxide and the stimulation of PG synthesis by hydrogen peroxide or oxygen radicals was progressively inhibited in the presence of arachidonic acid. Moreover, oxygen radicals stimulated the release of 14C-arachidonic acid previously incorporated in isolated glomeruli. This demonstrates that the increase in PG synthesis in response to oxygen radicals is due to activation of glomerular phospholipase by these radicals. This effect that is likely to occur at an early stage of experimental glomerulonephritis could play a role in the mechanism of the inflammatory process.

Animals↗
PubMed1977

Effects of Escherichia coli lipopolysaccharide on renal glomerular and tubular adenylate cyclase.

The effects of Escherichia coli lipopolysaccharide (LPS) on adenylate cyclase have been tested using renal tubular membranes and renal glomeruli isolated from rats. E. Coli LPS did not stimulate glomerular and tubular basal adenylate cyclase activity whereas it was an activator in the presence of fluoride. The effect of E. Coli LPS was immediate but was greater after 20 min preincubation. Maximum stimulation of both glomerular and tubular fluoride sensitive adenylate cyclase occurred at 125 microgram/ml of E. Coli LPS with an apparent Km (dose corresponding to 50% of maximum stimulation) of 30 microgram/ml. Above 125 microgram/ml there was a decrease in adenylate cyclase activity. E. Coli LPS produced an increase in the maximum velocity of both enzymes but did not affect their affinity for adenosine triphosphate. E. Coli LPS did not potentiate the effect of parathyroid hormone on glomerular and tubular adenylate cyclase. The lipid A moiety which is common to all LPS whatever the original strain gave results similar to those obtained with the entire LPS. This effect was specific and did not depend on the phospholipidic structure in general since no activation was obtained in the presence of phosphatidylserine.

Adenylyl Cyclases↗
PubMed1977

High affinity binding of 125I-angiotensin II to rat glomerular basement membranes.

125I-angiotensin II (AII) specifically bound to rat glomerular basement membrane (GBM). The kinetics of binding were similar to those obtained with the total glomeruli. The apparent dissociation constant was close to 50 pM with both preparations. The number of sites related to the amount of protein was two times greater with GBM than with total glomeruli. Since the amount of GBM protein extracted from a given amount of glomerular protein was about 10%, it was possible to estimate the share of the GBM binding sites for AII as representing 20% of the total number present in the entire glomerulus. Binding studies at equilibrium as a function of 125I-AII concentration and competitive binding experiments suggested either multiplicity of the binding sites or cooperativity in the binding reaction. Degradation of 125I-AII in the presence of GBM was slight and did not increase with time. The difference in the degrees of degradation of 125I-AII was too small to account for the observed difference in binding when the results obtained with GBM and isolated glomeruli preparations were compared. 125I-AII binding to GBM was increased after treatment of these membranes with collagenase, slightly diminished with neuraminidase, and almost completely abolished with trypsin suggesting the proteic nature of the receptor. 125I-AII binding to GBM was diminished after incubation of GBM with anti-GBM antibodies as a result of a decrease in the number of binding sites. 125I-AII binding was even more diminished in preparations of glomeruli isolated from rats passively immunized with anti-GBM antibodies when compared with glomeruli from control animals. This resulted from both smaller affinity for AII and decrease in the number of the binding sites. The present data provides evidence for specific binding sites for AII localized on GBM. This is noteworthy since receptors for polypeptide hormones are currently observed on the surface of cell membranes. These findings also suggest a new physiological role for AII which might involve modification of GBM permeability.

Angiotensin II↗
PubMed1977

[Comparative study of the formation of glycogen and trehalose during starvation in the Lepidoptera Bombyx mori L].

Glycogen reserves are entirely consumed during total starvation of Bombyx mori L. larvae. While the storage of glycogen is lowering and the dietary supply of carbohydrates stopped, the amount of trehalose also decreases but less rapidly than this of glycogen. Relative homeostasis is maintained but only for the ten first hours of inanition. Quantitative evaluation of blood trehalose, which is preformed more rapidly than glycogen analysis, might be used as an efficient test to characterized some physiopathological states.

Animals↗