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Biomedical subjects

A Astier

Publications and source records attributed to A Astier.

At least 73 records · Page 4Linked to original sources
PubMed1995

Inhibition of hydroxyl radical production by lactobionate, adenine, and tempol.

Superoxide and hydroxyl free radicals are strongly implicated in the deleterious effects of reperfusion of grafted organs. Iron ions are critical in the Fenton-like reaction that generates oxygen-free radicals from H2O2. Using the ADP/Fe2+/H2O2 .OH-generating system, we demonstrated that components of an organ-preservation solution (Henri Mondor solution): sodium lactobionate, adenine, and a nitroxide radical: 4-hydroxy-2,2,6,6-tetramethylpiperidine-n-oxyl (TEMPOL), showed unexpected inhibition properties on the production of hydroxyl radicals by complexation of Fe2+ for lactobionate and nitroxide or Fe3+ for adenine. This inhibition was 75.5% at 12 mM lactobionate. Moreover, a complete inhibition was observed at 50 mM. At 0.25 mM adenine, the reduction was 14.8% (maximum effect: 34.1%). Henri Mondor solution, at an identical adenine and lactobionate concentration, inhibited the radical production by 91.5%, indicating an additive effect. Nitroxide totally inhibited .OH production by the ADP/Fe2+/H2O2 system (maximum effect: 95.6%) and partially the production by an O2.- generating system (maximum effect: 74.8%). Thus, the association of these three components in preservation solutions would be an original method to limit the reperfusion injury observed in isolated ischemic organs.

Adenine↗
PubMed1995

Fenoverine-induced rhabdomyolysis.

Fenoverine is a spasmolytic drug that inhibits calcium channel currents. We describe the clinicopathologic findings in two patients with fenoverine-induced rhabdomyolysis, of whom one died. A transient left-bundle-branch block was observed in both patients. In one case, pre-existing hepatic dysfunction may have induced accumulation of the drug. Concurrent treatment by fibrates, as observed in the second patient, may have been a predisposing factor for fenoverine-induced rhabdomyolysis. The incidence of muscular complications of fenoverine therapy could be reduced by avoidance of prescription of the drug in patients with hepatopathy or those being treated with cholesterol-lowering agents. Physicians should be aware of life-threatening adverse effects of apparently innocuous drugs.

Aged↗
PubMed1995

Hypersensitivity to azathioprine mimicking gastroenteritis. Absence of recurrence with 6-mercaptopurine.

Hypersensitivity mimicking gastroenteritis is a rare complication of azathioprine therapy for which the mechanism is unknown. We report a case of devastating diarrhoea and vomiting due to azathioprine treatment in which hypersensitivity to the imidazole moiety of azathioprine was demonstrated. This has important therapeutic implications: in this situation, 6-mercaptopurine, which is the portion of azathioprine responsible for the cytotoxic therapeutic effect, can be administered without recurrence of side-effects.

Adult↗
PubMed1995

In vivo comparative study of two lactobionate based solutions for prolonged heart preservation.

The duration of safe heart preservation must be improved. Using a heterotopic heart transplantation model, we compared in vivo the recovery of rabbits hearts preserved with a K+Lactobionate based fluid (UW: University of Wisconsin solution) or with a Na+Lactobionate based fluid. In the "preservation" group, hearts were cold stored (4 degrees C) for 6 hours with UW (n = 9) or Na+Lactobionate solution (n = 9). In the "transplantation" group, cold storage was followed by 3 hours of reperfusion (UW: n = 8, Na+Lactobionate solution: n = 7). Functional recovery, adenine nucleotide pool, circulating blood cardiac enzymes, circulating blood and tissue malondialdehyde (MDA) were measured. Left ventricular end-diastolic and developed pressures at different preload levels were better after preservation with UW than with Na+Lactobionate solution (p < 0.05). Also with UW, adenosine diphosphate and total adenine nucleotide content were significantly higher than with Na+Lactobionate solution (p < 0.05) whereas adenosine triphosphate, monophosphate and energy charges were similar. Cardiac enzymes and tissue MDA were similar with UW and Na+Lactobionate solution. In circulating blood, MDA was not detected. These results enhance the superiority of UW solution over a Na+Lactobionate based solution for long term heart preservation.

Adenine Nucleotides↗
PubMed1994

Determination of fenoverine in tissue samples by high-performance liquid chromatography.

Fenoverine is a spasmolytic, non-anticholinergic phenothiazine derivative that inhibits calcium channel currents. We describe a high-performance liquid chromatographic method for the determination of fenoverine in striated muscle, smooth muscle, myocardium, and liver tissue. Reversed-phase liquid chromatography was performed on a 5 microns Nucleosil C18 column with acetonitrile-0.015 M phosphate buffer (28:72, v/v) as a mobile phase and detection with ultraviolet at 214 nm. The limit of quantitation of fenoverine in tissue samples was 25 ng injected. This method is well suited for the determination of fenoverine in various organs in animal experiments.

Animals↗
PubMed1994

Human epidermal Langerhans cells secrete a soluble receptor for IgG (Fc gamma RII/CD32) that inhibits the binding of immune complexes to Fc gamma R+ cells.

Langerhans cells (LC) express Fc gamma RII on their cell surface. In this paper, we demonstrate that these cells also release soluble Fc gamma RII (sFc gamma RII) molecules. LC express transcripts encoding a membrane-associated receptor and a transmembrane-deleted Fc gamma RIIA. The latter form was identified in LC culture supernatants using specific antibodies. CHO cells, transfected with LC-derived cDNA encoding the transmembrane-deleted Fc gamma RIIA, secrete sFc gamma RIIA that include the intracellular domain and exhibit the same backbone as the protein identified in LC supernatants. Secreted sFc gamma RIIA exhibits the same pattern of binding to human and mouse IgG subclasses as do membrane Fc gamma RII and inhibits the binding of immune complexes to Fc gamma RII+ cells. In addition, CHO cells expressing the membrane-associated Fc gamma RIIA release truncated and unstable Fc gamma RIIA molecules that lack the intracellular domain. Thus, sFc gamma RII can result from shedding of membrane molecules and/or from secretion of soluble receptors lacking the transmembrane domain.

Alternative Splicing↗
PubMed1994

Natural and recombinant soluble low-affinity Fc gamma R: detection, purification, and functional activities.

Studies on the identification, cloning, and biochemical characterization of natural and recombinant human and mouse low-affinity soluble Fc gamma R (sFc gamma R) have been developed using various methods. RT-PCR and/or biochemical analyses have demonstrated that low-affinity sFc gamma R (i) are generated by enzymatic cleavage of membrane-associated receptors or by an alternative splicing of the transmembrane region encoding exon and (ii) comprise only the extracellular domains or these domains plus the intracellular region of the membrane-associated molecules, respectively. Functional studies indicated that recombinant sFc gamma R bind mouse and human IgG subclasses with a binding profile identical to that of their membrane counterparts and inhibit Fc gamma R-mediated functions such as immune complex binding or ADCC. In addition, it has been demonstrated that a mouse recombinant truncated sFc gamma RII inhibits antibody responses to T-dependent antigens as well as B-cell proliferation and that a human recombinant truncated sFc gamma RIIIB blocks the Ig production by activated human peripheral blood mononuclear cells. Finally, different immunoassays devised to detect and quantitate circulating sFc gamma R showed that sFc gamma R serum levels vary in circumstances such as injections of protein antigens, in parasitic infections, in tumor-bearing mice, in patients with multiple myeloma (MM), or upon infusions of IgG or Fc gamma fragments in MM or immune thrombocytopenic purpura patients. The use of recombinant sFc gamma R, as well as the availability of monoclonal and polyclonal antibodies directed against different regions of these molecules, makes it possible to characterize further the biological effects of sFc gamma R and their biochemical and immunochemical characteristics, as well as to define their putative ligands on cell membranes.

Amino Acid Sequence↗
PubMed1994

Action of pentamidine-bound nanoparticles against Leishmania on an in vivo model.

The efficiency of antileishmanial agents may be enhanced by improving their bioavailability with a colloidal drug carrier. We have investigated the action of free pentamidine, compared with pentamidine bound to polymethacrylate nanoparticles, in a rodent model. BALB/c mice were infected, via the tail vein, with 4 x 10(7) L. major (MON 74) promastigotes. Twelve days after infection, seven groups of mice were treated respectively with methylglucamine antimoniate (Glucantime) 5.56 mg/kg i.p. x 5 d., pentamidine bound nanoparticles (100 microM), unloaded polymethacrylate nanoparticles, unloaded nanoparticles associated with free pentamidine (100 microM) 0.1 ml i.v. x 3 d and free pentamidine isethionate (2.28 mg/kg and 0.17 mg/kg i.v. x 3 d.). Twenty-one days post infection, the mice were sacrificed and the Leishmania load in the liver calculated from the number of amastigotes/500 liver cells and total liver weight in treated and untreated mice. Results demonstrated a 77% amastigote reduction in the group treated with targeted pentamidine relative to the control group. The ratio free pentamidine/bound-pentamidine was approx. 12.

Animals↗
PubMed1993

Detection and quantification of secreted soluble Fc gamma RIIA in human sera by an enzyme-linked immunosorbent assay.

Fc gamma RIIA can be produced in a soluble form that contains both the extracellular and intracellular regions of the receptor, due to an alternative splicing of the transmembrane domain-coding exon. We have developed an enzyme-linked immunosorbent assay (ELISA) that permits the specific detection and quantification in human sera of this secreted soluble Fc gamma RIIA. It uses the monoclonal antibody (MAb) IV.3 as capture antibody and rabbit polyclonal IgG directed against the intracellular region of Fc gamma RIIA as detector antibodies. The enzymatic reaction was amplified using an NADH/NAD+ amplification system. As little as 0.8-1.5 ng/ml (20-38 pM) of purified recombinant secreted Fc gamma RIIA could be detected. The serum levels of secreted sFc gamma RIIA ranged from 0 to 30 ng/ml in sera from 51 healthy donors. The mean value was 11.9 ng/ml +/- 6.55 (297 pM +/- 163) and the median value was 10.6 ng/ml (265 pM) (range: 0-764 pM).

Animals↗
PubMed1993

Chromatographic determination of volatile solvents and their metabolites in urine for monitoring occupational exposure.

The determination of volatile solvents and their metabolites in biological materials such as expired air, blood or urine allows the estimation of the degree of exposure of these chemicals. Chromatographic methods are now universally employed for this purpose and numerous analytical procedures are available for the determination of the most commonly used volatile solvents and their metabolites in urine. GC methods appear well adapted to the determination of the parent volatile solvents in blood and urine and may be used for the determination of their urinary metabolites, but these methods often require several prechromatographic steps. However, HPLC is becoming a powerful tool for the accurate and easy determination of urinary metabolites of volatile solvents, considering its decisive advantages for routine monitoring. Further, recent developments in HPLC could widen the usefulness of this method for most complex analytical problems that could be encountered during this measurement. However, despite the relative neglect of planar chromatography in this area of concern and considering the great interest in methods that could permit the simultaneous assay of numerous samples often required by routine monitoring, new approach using improved methods such as overpressured TLC could be very fruitful in the future.

Air Pollutants↗
PubMed1993

[In vitro study of leishmanicidal agents with drug carriers].

Antileishmanial chemotherapy is hampered by the location of parasites within lysosomal vacuoles of the macrophages which restricts the bioavailability of many potential antileishmanial compounds. In this study, the effectiveness of pentamidine targeted to the infected cells by a linkage to a colloidal drug carrier, methacrylate polymer nanoparticles was explored. In the same way, polyisoalkylcyanoacrylate nanospheres which have, in vitro, trypanolytic properties were also tested. The study was performed in an in vitro model using Leishmania major amastigote stages within the U 937 human monohistiocytic cell line. The antileishmanial activities of unloaded or pentamidine-loaded nanoparticles were compared to those of the free drugs. The 50% effective concentration of targeted pentamidine was 0.10 microgram/ml, while it was up to 2.7 micrograms/ml with the free drug after a 24-hour incubation time. The pentamidine-bound nanoparticles proved to be 25 times more active than the free drug. Unloaded polyisoalkylcyanoacrylate nanoparticles destroyed intracellular amastigote stages (50% EC = 15 micrograms/ml) but at a level close to the cytotoxic concentration.

Cell Line↗
PubMed1993

Soluble Fc gamma receptors.

Soluble Fc gamma receptors have been identified in biological fluids of mice and humans. They are produced either by alternative splicing of the exon encoding the transmembrane region of the receptor (Fc gamma RII) or by proteolytic cleavage at the cell membrane (Fc gamma RII and Fc gamma RIII). They inhibit B cell proliferation and immunoglobulin production. Their concentrations in plasma seem to be modified during the development of certain diseases, as for instance in multiple myeloma, where plasma concentrations of soluble Fc gamma RIII are correlated with the stage of the disease.

Animals↗
PubMed1992

Simultaneous high-performance liquid chromatographic determination of urinary metabolites of benzene, nitrobenzene, toluene, xylene and styrene.

A high-performance liquid chromatographic method is described for the simultaneous determination of six urinary metabolites of several aromatic chemicals: phenol (from benzene), hippuric acid (from toluene), 3-methylhippuric acid (from xylene), mandelic and phenylglyoxylic acid (from styrene) and 4-nitrophenol (from nitrobenzene). Reversed-phase liquid chromatography was performed in an isocratic mode at 1 ml/min on a 5-microns C18 column using two mobile phases: (A) acetonitrile-1% phosphoric acid (10:90); (B) acetonitrile-1% phosphoric acid (30:70). Phase A separates the six metabolites well, but phase B allows to a more rapid and reproducible simultaneous determination of phenolic compounds than phase A. For these compounds a prior enzymic hydrolysis step using Helix pomatia juice is performed to hydrolyse their sulphate and glucuronate conjugates. The reproducibility and the specificity are both excellent. Furthermore, the method is rapid, economical and easily automated. The proposed method appears very suitable for the routine monitoring of workers exposed to these chemicals on the basis of the biological threshold limit values.

Benzene↗
PubMed1992

Iso-immune neonatal neutropenia due to an anti-Fc receptor III (CD16) antibody.

We report a case of transient neonatal neutropenia due to a maternal iso-immunization against a non polymorphic region of the glycosylphosphatidylinositol-linked Fc receptor type III (CD16) on granulocytes. The mother's granulocytes were typed NA1-negative, NA2-negative and CD16-negative with human and monoclonal antibodies whereas her lymphocytes express the CD16 molecule. Expression of other markers were comparable to the controls. Flow cytometric analysis showed that maternal antibody recognized the granulocytes but not the lymphocytes from blood bank donors and that its binding was decreased on normal, phospholipase C-treated, granulocytes. The binding of commercial CD16 monoclonal antibodies was also dramatically decreased on normal granulocytes pre-incubated with maternal serum. The CD16 specificity of the antibody was confirmed by negative reactions with another CD16-deficient granulocytes. This observation leads us to conclude that cell-lineage specific differences of CD16 molecules are recognized by the patient's antibody. Moreover, we confirm that the absence of the FcRIII (CD16) on granulocytes is not associated with any pathology or susceptibility to infections and that, in the children, the blockade of this receptor by the maternal antibody only led to moderate neutropenia.

Adult↗
PubMed1992

Pharmacokinetics and absolute rectal bioavailability of hydrocortisone acetate in distal colitis.

The hydrocortisone pharmacokinetic profiles of hydrocortisone acetate foam (Proctocort) administered rectally was assessed in healthy volunteers and patients with ulcerative colitis or X-irradiation colitis. Endogenous production of hydrocortisone was suppressed by dexamethasone. Comparison of these data with those obtained after intravenous administration enabled assessment of absolute bioavailability, which was 30.0 +/- 15.1% in healthy volunteers vs. 16.4 +/- 14.8% in patients (P = 0.09). Maximal concentrations of hydrocortisone were also decreased in patients, 277 +/- 215 nmol/L vs. 610 +/- 334 nmol/L (P = 0.03). There was a nonsignificant tendency to faster absorption of hydrocortisone in patients vs. healthy volunteers, as the times to peak concentration were, respectively, 2.5 +/- 1.2 h vs. 2.8 +/- 0.8 h (P = 0.64), and the mean absorption times were 1.96 +/- 1.45 h vs. 2.54 +/- 1.62 h (P = 0.46). Thus, rectal inflammation resulted in a lower absorption of hydrocortisone. In addition systemic plasma levels remained in the physiological range, so that only minor side effects are to be expected.

Administration, Rectal↗