Biomedical subjects
S Abid
Publications and source records attributed to S Abid.
Protection against gentamicin-induced early renal alterations (phospholipidosis and increased DNA synthesis) by coadministration of poly-L-aspartic acid.
Coadministration of polyaspartic acid protects against functional and pathological signs of gentamicin-induced nephrotoxicity in rats without reduction of drug accumulation in renal cortex (Williams et al., J. Pharmacol. Exp. Ther. 237: 919-925, 1986; Gilbert et al., J. Infect. Dis. 159: 945-953, 1989). We have assessed the influence of polyaspartic acid on the early alterations induced in kidney cortex by gentamicin, namely the lysosomal phospholipidosis and the increase in cell turnover. We used an infused rat model in which animals received a total dose of 100 mg/kg of gentamicin over 12 hr. Renal cortex was examined 2 hr (day 0) and 48 hr (day 2) after treatment. All animals received an injection of [3H]thymidine (200 microCi i.p.) before sacrifice. Coadministration of polyaspartic acid (drug-polypeptide mass ratio 1:2.5) did not modify the drug serum levels, as recorded during or shortly after the infusion. Yet, it was associated with 1) an increased (approximately 35%) drug cortical content at day 0; 2) a significant protection against both biochemical (decrease of sphingomyelinase activity at day 0; increase of lipid phosphorus content at day 2) and morphological (enlargement of lysosomes and deposition of myeloid bodies at day 2) signs of lysosomal phospholipidosis in proximal tubular cells; and 3) an almost complete protection against increased cell turnover (mostly in proximal tubules) in cortex at day 2, as assessed by the measurement of [3H]thymidine incorporation into DNA and the enumeration of S-phase cells after histoautoradiography. In addition, morphological studies revealed a larger number of apical vacuoles in proximal tubular cells of animals receiving polyaspartic acid alone (but not in combination with gentamicin), and the deposition of osmiophilic, homogenous material in the lysosomes of animals receiving the combination of gentamicin and polyaspartic acid. Together with the results reported in two companion papers (Kishore et al., J. Pharmacol. Exp. Ther. 867-874, and 875-885, 1990), these results provide evidence that protection afforded by polyaspartic acid extends to the earliest cellular alterations described in kidney for gentamicin, namely the lysosomal phospholipidosis, suggesting that this protecting agent exerts blocking effect from this step in the cascade of events relating drug cortical accumulation to renal toxicity.
Comparative regenerative response of rat kidney cortex after treatment with therapeutic doses of aminoglycosides.
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Tissue repair in rat kidney cortex after short treatment with aminoglycosides at low doses. A comparative biochemical and morphometric study.
The tissue repair subsequent to aminoglycoside-induced tubular necrosis has been evaluated for five different derivatives given at low doses. Gentamicin, dibekacin, netilmicin, and tobramycin were administered intraperitoneally three times a day at 10 mg/kg per day; amikacin was given intraperitoneally twice a day at 37.5 mg/kg per day. The drugs were administered for 4 or 10 days. Tissue regeneration in kidney cortex was assessed by: the rate of DNA synthesis (i.e., the specific radioactivity of DNA measured 1 hour after intraperitoneal injection of 200 microCi of [3H] thymidine per animal); the occurrence of less differentiated cells estimated by the morphometry of peroxisomes. In mature cells, identified by the presence of drug-induced myelin-like figures, peroxisomes occupied 3.0% of the cytoplasmic area, whereas in less differentiate cells devoid of myelin-like figures, the same organelles made 1.4% of the cytoplasmic area (mean values obtained from 20 treated animals). Gentamicin and amikacin were both shown to induce a dose-related enhancement of DNA synthesis in kidney cortex, except that the latter antibiotic was about 10 times less potent as compared to the former. When the five drugs were compared on the basis of their effect on DNA synthesis after 10 days of treatment, they gave the following ranking: gentamicin (5.6 times the mean control value) greater than or equal to dibekacin greater than netilmicin greater than tobramycin greater than amikacin (1.6 times the mean control value). The differences were less striking after 4 days of treatment. For each antibiotic, sections of proximal tubular cells obtained from four animals treated for 10 days (total surface, 2.10(4) microns2) were scanned for the presence of regenerative tissue (areas poor in peroxisomes). In gentamicin-treated rats, the areas poor in peroxisomes represented more than 18% of the scanned cytoplasmic surface in proximal tubular cells, as compared to about 4.5% in controls. The ranking of the five antibiotics according to the estimated area of undifferentiated tissue in proximal tubules was parallel to that found for DNA synthesis i.e., in gentamicin-treated rats undifferentiated tissue was much more prominent, as compared to amikacin-treated animals (about 6% of the scanned area). Since the relative extent of kidney cortex regeneration induced by each antibiotic at low dose is likely to reflect the degree of tubular necrosis, we conclude that the ranking outlined above indicates a difference in potential nephrotoxicity.
[CT diagnosis of perceptive deafness: 42 cases].
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[NA, a specific system for polymorphonuclear neutrophils: localization, biochemistry, genetics, frequency role in pathology].
Among the neutrophil polynuclear specific antigens (NA, NB, ND, NE, ...), NA antigen is the most common. It is a glycoprotein situated on the neutrophils FcRIIIb-receptor and presents 2 forms: NA1 and NA2. The epitope responsible of that polymorphism has got an amino acids composition that is unknown. The first techniques used for their analysis were the microagglutination and the granulocytotoxicity-later, the immunofluorescence, the chemiluminescence and the MAIGA (Monoclonal Antibody Immobilized granulocyte Antigen) were introduced. These last years, more efficient techniques appeared like Flow Cytometry and Polymerase Chain Reaction (PCR) that allowed phenotyping and genotyping of neutrophil polymorphonuclear specific antigens. The studies indicated that NA antigen frequency varies according to the populations and the ethnics. NA2 allelic form is more frequent than NA1 in the caucasian population (88% VS 46%). In human pathology, NA antigen is implicated in the physiopathological mechanisms of the alloimmune and probably auto-immune neutropenies.