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Biomedical subjects

J Cambar

Publications and source records attributed to J Cambar.

At least 55 records · Page 3Linked to original sources

[Effect of verapamil on cyclosporine-induced vasoconstriction in human or murine isolated glomerules].

Cyclosporin is a very potent immunosuppressant, but it often produces renal disturbances which limit its clinical use. Using an image analyzer which determines the areas of isolated glomerules, we were able to demonstrate that cyclosporin in various concentrations exerts a direct vasoconstrictive effect on human and murine glomerules. We also showed that verapamil has an almost total inhibitory effect on cyclosporin-induced vasoconstriction. These findings seem to be of interest in clinical practice to reduce the nephrotoxicity of cyclosporin.

Animals↗

Seasonal effects on the daily variations of gentamicin-induced nephrotoxicity.

The effect on kidney damage of the season of year at which gentamicin was administered to rats was studied. Rats received a single intramuscular dose of 200 mg/kg gentamicin at four different times of the day (08.00, 14.00, 20.00 or 02.00 hours. Studies were carried out in January-February, March-April, June-July and October-November. The nephrotoxicity was assessed by the increase of three urinary enzymes: two brush border enzymes, gamma-glutamyl transferase and alanine aminopeptidase, and a lysosomal enzyme: N-acetyl-beta-D-glucosaminidase. The results show that when the injection is administered at 20.00 hours in the January-February and the October-November studies and at 08.00 hours in the March-April study and at 14.00 hours in the June-July study there is a significant increase in the excretion of these enzymes. The renal toxicity of gentamicin therefore has circadian variations as well as seasonal variations. The peak enzyme level is displaced from the start to the end of the rest period of rats depending upon the time of year.

Acetylglucosaminidase↗

[Isolation of tubular proximal cells of the human kidney by affinity chromatography using Lotus tetragonolobus lectin].

An affinity chromatography technique, using a lectin issued from Lotus tetragonolobus as ligand, and coupled to Sepharose 6MB support, has been chosen to enrich a cellular population in tubular proximal cells. Cell desorption was obtained with a competitive sugar, L Fucose. Intensive enzymatic brush border activity, shown in selected cells compared with initial cellular mixture, evidenced an enrichment in proximal tubular cells. These results prove that lectin use as ligand in affinity chromatography permits the separation of renal cell populations and presents the advantage that the bound cells can be recovered by a gentle competitive elution for further cultures.

Cell Separation↗

[Demonstration of direct vasoconstrictive effect of cyclosporin on glomeruli isolated from human kidney].

Cyclosporin (CsA), a potent immunosuppressive agent, can induce severe renal damage, characterized by lesions in the tubulo interstitial region and decreased renal function. Isolated glomeruli can be considered as a fruitful model to evidence the direct effect of drugs at the level of glomerular structures. The present study aims to evidence, in this model, vasoactive response of isolated human renal glomeruli induced by different CsA concentrations. Area changes of such isolated glomeruli can be assessed by a semi-automatic morphometric method, using a video-camera device coupled with a microprocessor (Biocom 2000). Experiments are done under double bind conditions. CsA-induced decrease in glomeruli area is dose- and time-dependent. CsA effect is rapid in that glomerular area is significantly decreased even after 5 min. incubation; vasoconstrictive effect is more important (and maximum) after 10 min. incubation; significant decrease can be noted with 10(-7) M (-11.41%) and 10(-6) M (-10.26%). In conclusion, the isolated glomerulus model allows us to demonstrate the direct vasoconstrictive effect of CsA, that can in part explain the renal functional changes and the acute renal failure often described in human clinic.

Analysis of Variance↗

[Circadian variation of the nephrotoxicity induced in rats by bi-daily repeated administration of amikacin].

We have studied the chrononephrotoxicity of amikacin during and after a prolonged treatment in rats. Animals received by intramuscular route a daily dose of 400 mg/kg (in two times) during 7 days at two different times (8.00 - 20.00 and 14.00 - 2.00). Large time-dependent variations in renal injury had been evidenced by several parameters and particularly by enzymuria. This injury is maximal when administration is made at 14.00 - 2.00. These data confirmed our results obtained in previous investigations with single daily injections and evidence that chrononephrotoxicity could permit an optimization of nephrotoxic drugs largely used in clinics.

Acetylglucosaminidase↗

[Morphologic and enzymatic characteristics of healthy human kidney epithelial tubular cells in culture].

The present study defines morphological and enzymatic characteristics of human healthy renal tubular cells in primary culture, and during three passages. The results confirm the ability to culture human renal tubular cells and to quantitatively evaluate the activity of specific tubular enzymes in the cells and in the culture medium. Such determinations can be compared to similar enzyme activity research in renal biopsies or in urines, to investigate human renal cell functions, in clinical, pharmacological or toxicological approaches.

Alkaline Phosphatase↗

[Effect of cisplatin on healthy human renal tubular cells and cancerous cells in culture].

An in vitro comparative cis-platin cytotoxicity was evidenced in human renal normal and tumoral cultured cells. Cytotoxic effect was estimated at membrane level by intracellular enzymatic markers release into culture medium and nuclear level by ADN synthesis inhibition after 3H thymidine incorporation. These results show a more intensive activity of cis-platin in normal tubular cells than in tumoral ones.

Cells, Cultured↗

Circadian variations in the renal toxicity of gentamicin in rats.

The hypothesis that sublethal doses of aminoglycosides cause renal tubule disorders resulting in changes of urine enzyme levels was investigated. The renal status following injection of a single sublethal dose of gentamicin (200 mg/kg) at different times during a 24 h cycle was studied. Increased excretion of gamma-glutamyl transferase, alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase, used clinically as markers for tubule toxicity of aminoglycosides, was maximal when gentamicin was administered to rats at 2 p.m. and was minimal when injected at 8 p.m. These significant differences in enzyme excretion as a function of injection time are correlated with the concentration of gentamicin in the urine and in the renal cortex.

Acetylglucosaminidase↗

[Demonstration of seasonal variations of circadian rhythm in gentamicin-induced chrono-nephrotoxicity in rats].

The present study investigates the chronobiological approach of the gentamicin-induced nephrotoxicity in rats treated with a single sublethal dose administered at different times of day and season of year. The nephrotoxicity is appreciated by gamma-glutamyl-transferase and alanine-amino-peptidase, two enzymes of the brush border cells and N-acetyl-beta-D-glucosaminidase, a lysosomal enzyme. These excretions peak out at 8 p.m. and reach a through at 8 a.m. for the experimentation in january-february. In contrast, for the experimentation in June-July, we evidence gamma-glutamyl-transferase and alanine aminopeptidase excretion increased at 2 p.m. and decreased at 8 p.m. So, we evidence with gentamicin not only a circadian but also a seasonal susceptibility in rats.

Acetylglucosaminidase↗

[Quantitative approach of melanin in human cultured melanocytes].

The purpose of the study was to establish an in vitro model for the quantification of the melanin produced in human melanocytes in culture. Melanin content in these cultured human melanocytes is determined by spectrofluorimetric assay. Fluorescence intensity is quantitatively related to the melanin content present in cultured melanocytes.

Cell Count↗

Circadian rhythm in gamma glutamyltranspeptidase and leucine aminopeptidase urinary activity in rats.

Urinary gamma glutamyltranspeptidase (GGT) and leucine aminopeptidase (LAP), renal tubular brush border enzymes, have been shown to be sensitive indicators of renal tubular functions. This study documents circadian rhythms in the urinary activity of GGT and LAP, statistically validated and quantified by the cosinor method, in 15 male Wistar rats standardized to a LD 12:12 illumination schedule (light from 0800 hr to 2000 hr) and fed ad libitum. The acrophase of the circadian rhythms in urinary GGT and LAP activity occurred at the end of the rest span of the animals: between 1730 and 1915 for GGT (depending on the mode of expression of the activity) and between 1700 and 1910 for LAP. Of striking resemblance in their timing, both these rhythms were also of large amplitude (about 50% of the mesor for urinary GGT activity and about 45% for LAP one). The circadian acrophases of urinary GGT and LAP activity led in timing the circadian rhythms in urine volume and creatinine excretion by about 13 hr. Such findings consistent with the circadian variations found by other investigators in GGT in kidney homogenates or in LAP in human urine thus reflect a periodicity in renal tubular function. The reasons for these circadian variations, still unknown at this time, are discussed. The influence recently demonstrated of the hormonal context on protein and enzyme synthesis at the tubule, and its phase relations to urinary enzyme excretion emphasize how much the circadian rhythm in urinary GGT and LAP activity is well included in the murine time structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Importance of urinary enzymes as a marker of post-ischemic proximal tubular involvement in rat].

We have studied in rats the influence of renal ischemia on urinary excretion of three brush border membrane enzymes (gamma glutamyl transferase, alkaline phosphatase and leucine aminopeptidase) and of a lysosomal one (N-acetyl-B-D-glucosaminidase). Urines were collected over 24 hours periods during three days before and after a 45 minutes renal artery clamping. Urinary GGT, PAL and LAP excretion were significantly increased on the first day after renal ischemia, but returns to normal values on the second day. Urinary NAG activity increases on the first day, but contrary to the latter enzymes, reached to normal values only on the third day. Enzymuria seems to be a useful marker of tubular injury occurring after a temporary renal ischemia in the rat.

Acetylglucosaminidase↗

[Demonstration of seasonal changes of circadian rhythms of amikacin chrononephrotoxicity in rats].

The present study investigates the chronobiological approach of the amikacin-induced nephrotoxicity in rats treated with a single sublethal dose administered at different times of day. The nephrotoxicity is appreciated by gamma-glutamyl-transferase and N-acetyl-beta-D-glucosaminidase urinary excretion, respectively a brush border and a lysosomal enzyme. These excretions peak out at 14:00 and reach a through at 20:00. In contrast, in a precedent experimentation, in october/november, we evidence gamma-glutamyl-transferase excretion increased at 20:00. So, we evidenced with amikacin not only a circadian but also a seasonal susceptibility in rats.

Acetylglucosaminidase↗

[Chrononephrotoxicity of amikacin after 7-day chronic poisoning in rats].

We have studied the chrononephrotoxicity of amikacin during and after a prolonged treatment in rats. Animals received by intramuscular route a daily dose of 400 mg/kg during 7 days at four different times (08:00, 14:00, 20:00 or 02:00). Large time-dependent variations in renal injury had been evidenced by several parameters and particularly by enzymuria. This injury is maximal when administration is made at 14:00. These data confirmed results obtained in previous investigations. The knowledge of chrononephrotoxicity could permit an optimization of drugs in clinics.

Acetylglucosaminidase↗