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N Seta

Publications and source records attributed to N Seta.

66 records · Page 4Linked to original sources

Asialoglycoprotein receptor in human isolated hepatocytes from normal liver and its apparent increase in liver with histological alterations.

We have characterized a binding site for galactosyl terminal glycoproteins in hepatocytes isolated from human biopsies. The binding of asialoorosomucoid on hepatocytes previously treated by Triton X-100 was saturable, calcium-dependent and highly affine (Ka = 1.11 +/- 0.87.10(9) M-1) thus corresponding to a ligand-receptor binding. The total number of receptors in the normal human liver was 140,000 +/- 65,000 sites per cell. This corresponded to the value obtained in the human hepatoma cell line HepG2, but was significantly lower than for isolated rat hepatocytes. Furthermore, in hepatocytes isolated from livers with histological features of either fibrosis, cirrhosis, hepatocarcinoma with cirrhosis or nodular regenerative hyperplasia, the number of asialoglycoprotein receptors per cell was increased, while the binding affinity was unchanged.

Adult↗

Limited protection by small unilamellar liposomes against the renal tubular toxicity induced by repeated amphotericin B infusions in rats.

Amphotericin B (AMB), either alone or incorporated into small unilamellar vesicles of pure dipalmitoylphosphatidyl choline (DPPC SUV-AMB), was administered intravenously to male Sprague-Dawley rats once daily for 5 days. Either 1.5 or 3.5 mg of AMB or DPPC SUV-AMB per kg was given, since these concentrations corresponded, respectively, to the lowest nephrotoxic dose and the sublethal dose of AMB in our model. Tubular functions were evaluated daily, and AMB concentrations in plasma, urine, and tissues were measured by high-performance liquid chromatography. AMB at both doses induced tubular toxicity, hyposthenuria being the earliest symptom. DPPC SUV-AMB at 1.5 mg/kg/day was atoxic, but the tubular alterations induced by 3.5 mg of DPPC SUV-AMB per kg were similar to those observed with 3.5 mg of AMB per kg, except that the ability to concentrate urine was partly restored 72 h after the last infusion. Incorporating AMB into DPPC SUV did not influence the pharmacokinetics of the drug. Using this lipidic AMB formulation, we thus observed a beneficial effect toward limiting the renal tubular toxicity of repeated low doses of AMB but, unexpectedly, not that of high doses. These results indicate that tubular renal functions and electrolyte serum values should be closely monitored in patients treated with AMB liposomal formulations, especially high-dose regimens.

Acetylglucosamine↗

Polyclonal antibody-based enzyme-linked immunosorbent assay of alpha 1-acid glycoprotein.

This is a noncompetitive enzyme-linked immunosorbent assay for measuring low concentrations (2 to 100 micrograms/L) of human alpha 1-acid glycoprotein (AGP; orosomucoid). The method is based on a simple "sandwich" technique involving polyclonal rabbit antisera against AGP. Mean within-run and total (between-run) CVs were 6.2% and 9.7%, respectively. Analytical recovery, tested in various biological fluids, averaged 101%. The technique has been successfully applied to diluted biological fluids such as bronchoalveolar lavage, cerebrospinal and amniotic fluids, and hepatocyte-culture supernates. Because of its analytical validity and the commercial availability of the reagents, this assay is suitable for large-scale determinations of AGP concentrations in those biological fluids in which its concentration is relatively low.

Amniotic Fluid↗

Microheterogeneity of the carbohydrate moiety of human alpha 1-acid glycoprotein in two benign liver diseases: alcoholic cirrhosis and acute hepatitis.

To determine whether alterations of the carbohydrate moiety of human alpha 1-acid glycoprotein constitute a marker of hepatic damage we studied purified alpha 1-acid glycoprotein from healthy individuals and two groups of patients with benign liver diseases: alcoholic cirrhosis and acute viral hepatitis. The results indicate: (1) increased concanavalin A-non reactive forms in cirrhosis and hepatitis, (2) a markedly increased proportion of fucosyl residues in all cirrhotic and some hepatitis patients. Although hyperfucosylation is generally considered to be a tumor marker, the observation here in the two benign liver diseases indicates that an increased fucosyl content should be considered as a more general expression of pathological glycoconjugate metabolism.

Acute Disease↗

Reduction in biliary excretion of ceftriaxone by diclofenac in rabbits.

The effects of diclofenac, a nonsteroidal anti-inflammatory drug, on biliary excretion of ceftriaxone were evaluated in rabbits. In a previous study, we demonstrated that diclofenac increased the extravascular diffusion and antibacterial efficacy of ceftriaxone without any effect on serum protein binding and urinary excretion of this antibiotic. We perfected a surgical procedure that allowed the study of biliary secretion in conscious rabbits with a stable hemodynamic state. The kinetic study was carried out on the fourth day of treatment with ceftriaxone alone (30 mg/kg per day given intramuscularly; group 1) or combined with diclofenac (1.5 mg/kg per 12 h given intramuscularly; group 2). Cumulative biliary excretion of ceftriaxone over 6 h was significantly reduced in group 2 (5,291.6 +/- 2,017.5 micrograms in group 1 versus 1,379.1 +/- 567.1 micrograms in group 2). This phenomenon occurred without any change in biliary flow. Indocyanine green clearance (20 mg/kg) increased in animals treated with ceftriaxone alone compared with the saline-treated control group (55.04 +/- 4.68 versus 33.29 +/- 7.52 ml/min per kg, respectively). Diclofenac alone caused a significant decrease in indocyanine green clearance compared with clearance in controls (25.05 +/- 4.74 versus 33.29 +/- 7.52 ml/min per kg), and indocyanine green clearance appeared not significantly different from control values in animals receiving ceftriaxone plus diclofenac. These results suggest that (i) ceftriaxone could increase hepatic blood flow and (ii) reduction of the hepatic clearance of ceftriaxone by diclofenac may be due to hepatic hemodynamic variations involving diclofenac inhibition of prostaglandin synthesis, although an interaction of diclofenac with hepatic uptake of ceftriaxone cannot be ruled out.

Animals↗

Incorporation of amphotericin B (AMB) into liposomes alters AMB-induced acute nephrotoxicity in rabbits.

To investigate the protective effect of liposomes on acute amphotericin B (AMB) renal toxicity, we compared in rabbits the acute toxicity of 4 mg/kg of free-AMB and 4 or 10 mg/kg of liposomal AMB (L-AMB) during 90 min after antibiotic infusion. Free-AMB exhibited immediate nephrotoxicity with a 44% decrease of the glomerular filtration rate and alteration of tubular cell membrane permeability expressed as increases in urinary pH (6.5 vs. 4.7), potassium fractional excretion (95% vs. 30%) and sodium fractional excretion (26% vs. 4%). Urinary excretion of the lysosomal enzyme N-acetylglucosaminidase was unchanged by free-AMB. Incorporation of AMB into liposomes prevented the toxic effects of free-AMB on glomerular filtration and tubular cells membrane, but significantly increased N-acetylglucosaminidase urinary excretion (380 and 180% in animals receiving 4 and 10 mg/kg of L-AMB, respectively). Absolute AMB urinary excretion during the experiment was unchanged by liposomes and was always less than 1% of the total dose administered. Liposomes alone exhibited no toxicity. These results suggest that liposomes could increase the interaction between AMB and lysosomes leading to an additional mechanism of cellular injury. They admonish close monitoring of renal function and enzymuria in clinical situations in which L-AMB is being used.

Amphotericin B↗

Tolerance of once-daily dosing of netilmicin and teicoplanin, alone or in combination, in healthy volunteers.

The purposes of this study were to test the pharmacokinetics and renal and otologic tolerances of a once-daily regimen of netilmicin and teicoplanin administered intramuscularly, alone or in combination (4.5 and 6 mg/kg, respectively), for 7 days in 30 healthy male volunteers. Teicoplanin induced only a mild increase in enzymuria. Nephrotoxicity was moderate and reversible with netilmicin; there was increased enzymuria and alteration in diluting ability, without significant changes in urinary beta 2-microglobulin levels, concentrating ability, and glomerular filtration rate. Ototoxicity was not detected in any of the subjects. Our results suggest that (1) teicoplanin and netilmicin given once daily induced only slight, reversible tubular damage, without any sign of ototoxicity; (2) their combination was not more toxic; and (3) clinical studies can be envisaged to evaluate the efficacy and tolerance of once-daily regimens in long-term treatment.

Acetylglucosaminidase↗

Nasal epithelial and inflammatory response to ozone exposure: a review of laboratory-based studies published since 1985.

This article summarizes biological events in human and animal nasal epithelium after short- and long-term exposure to ozone, the principal agent in photochemical smog. Despite anatomical and histological interspecies differences, ozone exposures resulted in common nasal qualitative alterations with an anterior-posterior gradient of phenomena occurring immediately, and with a lag time postexposure: epithelial disruption and increased permeability, inflammatory cell influx, and proliferative and secretory responses. Described mechanisms of toxicity included a direct effect of ozone on epithelial lining fluid and cellular membranes and the subsequent release of cytokines and cyclooxygenase and lipoxygenase products. An indirect effect of ozone was indicated by a decreased mucociliary clearance, free radicals production interacting with a gene promoting factor, and increased DNA synthesis. Studies highlighted the pivotal role of activated neutrophils and mast cells leading to the release of deleterious enzymes (tryptase, eosinophil cationic protein) and numerous cytokines. Experiments performed with ozone exposure/allergen challenge reported that, besides the intrinsic deleterious properties of ozone, it also had a priming effect on the late-phase response to allergen challenge, providing new insights into the pathophysiology of respiratory allergic diseases.

Animals↗

Insecticide urinary metabolites in nonoccupationally exposed populations.

The wide use of insecticides in agricultural and residential settings has resulted in environmental contamination, leading to increased concern about exposure of the population and possible chronic effects on health. This review summarizes the studies that have measured urinary metabolites to assess exposure of nonoccupationally exposed population to nonpersistent insecticides, organophosphates (OPs), carbamates, and pyrethroids. Electronic search yielded 36 different studies performed in a small number of countries for the last 20 years, most of them dealing with OP urinary metabolites. Dialkylphosphates, specific metabolites of OPs, and specific metabolites of pyrethroids or carbamates, have been investigated. Results indicate that a wide range of the population, adults as well as children, is exposed to OPs and to a lesser extent to pyrethroids and carbamates. Levels are one to several orders of magnitude lower than those in occupational studies. The contribution of the different sources of insecticide exposure remains uncertain. Food contamination, as well as environmental and residential contamination, appears to influence exposure, especially in the case of children. Residential use of insecticides, having pets, and living near gardens or fields have all been inconstantly related to higher urinary metabolite levels. Occupational exposure of the parents, especially of the agricultural workers, seems to be a predictive factor of higher exposure of their children. More studies investigating every source and pathway of exposure of randomized population samples and in other countries than the United States, in particular in developing countries, could improve our knowledge of factors influencing insecticide exposure of the population.

Animals↗

Cytomegalovirus infection in patients with systemic lupus erythematosus.

Cytomegalovirus (CMV) infection is known to induce several autoimmune abnormalities in mice that resemble those found in systemic lupus erythematosus (SLE). In addition, a potential role for CMV in the development and/or progression of SLE has been suggested. In order to further clarify this issue, we reviewed the relationship between SLE and CMV infection on the basis of the clinical and immunological features of cases reported in the literature and our own patients.

Adolescent↗