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J Cambar

Publications and source records attributed to J Cambar.

At least 73 records · Page 4Linked to original sources

[Chronobiology and renal physiopathology].

This review presents our recent knowledge in renal chronobiology, considering physiology, pathology, pharmacology and toxicology. In a first part, are described renal chronophysiological data, pointing out particularly urinary excretion rhythms, largely described for last century. Such physiological observations lead to conclude that renal structures and functions present large temporal variations. Endogenous and exogenous origins of these rhythms are widely discussed. Evidence of such circadian and circannual variations in these renal structures and functions permit to understand why different agents, pathogeneous, toxic or medicamentous, will present time-dependent effects at renal level. So, a second part presents some recent experimental and clinical data in chrononephrology, chronopharmacology and chrononephrotoxicity. Finally, the concept of renal chronesthesy is presented and discussed, in order to explain these temporal variations in renal target susceptibility to different substances acting at this level.

Animals↗

[Circadian variations of amikacin nephrotoxicity in rats].

We have studied the circadian variations in the nephrotoxicity of a single dose of a recently developed aminoglycoside, amikacin, in rats. Male rats placed in cages providing constant thermal conditions and lighted from 08:00 to 20:00 h were given a single intraperitoneal injection of 1.2 g/kg amikacin at different times of the 24 hour cycle (08:00, 14:00, 20:00 or 02:00). The study was carried out in October/November. Several parameters were monitored, including urinary excretion of gamma-glutamyl transferase, an enzyme found in the brush border of proximal tubule cells. The increase in urinary excretion of gamma-glutamyl transferase (expressed as a percentage) was found to vary according to the time of administration of amikacin. The highest GGT excretion occurred following administration of amikacin at 20:00 (484% +/- 62.75) and the lowest excretion, similar to that observed in controls, was found following administration at 14:00 (127% +/- 16.85). Thus, it seems that circadian variations in amikacin nephrotoxicity exist in rats. In a previous study we had found circadian variations in acute amikacin nephrotoxicity in mice. A thorough knowledge of these phenomena would improve our use of antibiotics in human clinical practice.

Amikacin↗

[Influence of 3 beta-blockers on the diameter of glomeruli isolated from the renal cortex of rats].

The purpose of the study was to determine a direct vascular effect of beta-blockers on isolated glomeruli of rat kidney. The glomeruli were isolated by sieving and their diameters measured with a micrometer before and after addition of each of three beta-blockers. The diameter of the glomeruli increases (6,7%) with verapamil, a calcium inhibitor, but remains unchanged in the same experimental conditions as well with propranolol, drug which decreases renal plasma flow, than with nadolol and tertatolol, drug increasing renal haemodynamics. The location and the mechanism of the glomerular vasoactivity of these different beta-blockers are discussed.

Adrenergic beta-Antagonists↗

[Chronotoxicity of amikacin].

This study addresses circadian variations in the tolerance of mice to a single lethal dose of amikacin. Female mice placed in cages providing constant thermal conditions and lighted from 8 h to 20 h were given a single intraperitoneal injection of 1.6 to 1.9 g/kg amikacin at different times over the 24 hours (8 h, 14 h, 20 h and 2 h) and in two different seasons (november/december and march/april). The number of dead mice was determined every day for seven consecutive days. For a given dose, mortality rate was influenced by the time and season of administration of amikacin. Amikacin toxicity exhibited a peak at 2 h (mean 60%) and nadir at 14 h (mean 47.75%) in november/december, whereas the opposite was true in spring (means 36.6% and 23.3% respectively at 14 h and 2 h). Thus, acute toxicity of amikacin in mice varies throughout the circadian cycle and from season to season. These findings encourage further research in view of achieving optimal use of antibiotics in human clinical practice.

Amikacin↗

Effects of verapamil--a calcium inhibitor--on the vasomotor response of cortical and juxtamedullary glomeruli of the human kidney.

Cortical and juxtamedullary glomeruli of the human kidney were isolated by sieving. Verapamil, a calcium inhibitor, was added to a suspension of the glomeruli. The vasomotor response was measured by a video analyser. We were thus able to determine the modification of the cortical and juxtamedullary glomeruli surface area. Only the cortical glomeruli became vasodilated in response to the calcium inhibitor.

Humans↗

[Comparative study of the vasoreactivity of isolated human cortical and juxtamedullary glomeruli using verapamil and dopamine].

The purpose of the present study was to compare the area variations of human cortical and juxtamedullary glomeruli after incubation with verapamil and dopamine. The glomeruli were isolated by sieving; areas were measured by a video analyser. The surface of the cortical glomeruli increases largely with verapamil (+14,3%) and dopamine (+11,5%). But, the area of the juxtamedullary glomeruli remains unchanged in the same experimental conditions. Evidence of such a vasoreactivity difference between cortical and juxtamedullary glomeruli will permit a better understanding in the regulation of renal haemodynamics.

Dopamine↗

[Circadian variations of the mortality of mice due to cadmium sulfate].

If circadian variations in tolerance to drugs have been often demonstrated, such observations about heavy metals are still very scarce. The present study proposes to determine if circadian variations occur in the tolerance of Mice to single lethal dose of cadmium sulphate. 400 female mice, kept in cages on a 8.00-20.00 L/D cycle, received IP a single cadmium sulphate injection at different doses (2.5, 3, 3.5 and 4 mg/kg) at different hours in the day (8.00, 14.00, 20.00 and 2.00 hrs.). Death number was determined each day during 10 consecutive days. The mortality percentage is a function of the time of the cadmium administration, varying between 3.3 and 21.7% for 2.5 mg/kg, between 16.7 and 43.3% for 3 mg/kg, between 33.3 and 71.7% for 3.5 mg/kg and between 73.3 and 96.7% for 4 mg/kg. The metal is the most toxic at 20.00 hr (mean: 58.3%) and the least at 2.00 hr. (mean: 33.7%). A circadian susceptibility to cadmium sulphate in Mice thus clearly appears, as has been recently described with mercury and platinum.

Animals↗

[Comparative study of circadian changes of the mortality of mice with respect to 2 aminoglycosides, gentamycin and dibekacin].

We compare the acute toxicity of a dose of gentamicin or dibekacin in Mice at different times of the day. The female Mice are housed with food and water ad libitum for one and half week, ten or fifteen per cage in a light controlled room (lights on from 8 to 20 hrs). Each animal was given gentamycin (250, 275, 300 or 325 mg/kg) intramuscular and dibekacin (320, 355, 390, 425 or 460 mg/kg) at one of four times: 8, 14, 20 and 2 hrs). After injection, the animals are kept in their cages and observed for 10 days. We show that the circadian biosusceptibility rhythm in dibekacin toxicity is similar to that of gentamycin with significant differences in the mortality at the four hours. There is an evident parallelism between the curves for gentamycin and dibekacin but the differences in the percentage of mortality rate are more important for gentamycin than for dibekacin.

Animals↗

[Ciradian variation in the lethal dose 50 of mercuric chloride in mice].

If circadian variations in tolerance to drugs have been often demonstrated, such observations about heavy metals are still very scarce. The present study proposes to determine if circadian variations occur in the tolerance of Mice to single lethal dose of mercuric chloride. 360 female Mice, kept in cages on a 8.00 - 20.00 L/D cycle, receive I.P. a single mercuric chloride injection at different concentrations (100 to 300 X 10(-6)) at different hours in the day (8.00 - 14.00 - 20.00 or 2.00). Death number is determined each during 10 consecutive days. For the highest doses causing death (from 200 x 10(-6)), the mortality percentage is a function of the time of the mercury administration. The metal is the most toxic at 20.00 (LD50: 4,14 +/-0,47) mg/kg) and least at 2.00 (LD50: 5,54 +/- 0,18 mg/kg). Moreover, death occurs later at 2.00 than at other times. So a susceptibility to mercuric chloride in Mice clearly appears.

Animals↗

[Demonstration of 2 distinct glomerular populations by a sieving technic in the kidney cortex of the pig].

Amelioration of sieving technics for glomeruli isolation aims at obtention of purer and more homogeneous preparations, presenting a high preservation degree for glomerular functional studies. We have recently demonstrated the necessity to use sieves adapted to the glomeruli size of different considered animals as well as to use kidneys having exactly the same weight in order to obtain very homogeneous glomeruli suspensions. This study presents a new amelioration in the homogeneity of the glomeruli diameter through a preliminary dissection of the renal cortex in order to isolate glomeruli situated in the same particular cortical zone. Pig renal cortex, because of its size, agrees well with a fine dissection in order to dissociate the superficial and the juxta-medullary zones. Glomeruli are isolated with 160/120 micro mesh sieves. Diameter mean value is 218.8 +/- 30.1 micro in superficial glomeruli and 270.4 +/- 30.1 micro in juxta-medullary ones, highly significant difference, (p less than 0.001). Moreover, repartition frequency histograms of the juxta-medullary glomerular populations diameter presents a large shifting to higher values. This renal dissection preceding the glomeruli isolation sieving technique contributes to better the homogeneity of the isolated glomeruli suspensions and opens the way to the original study of the comparative in vitro vasoreactivity of these two different glomerular populations after incubation with physiological or pharmacological reagents.

Animals↗

[Circadian rhythms in rat and mouse urinary electrolytes and nitrogen derivatives excretion (author's transl)].

The present study considers circadian rhythms of excretion of six solutes in the urine of 40 rats and 100 mice collected during eight consecutive, six-hour long periods. 1. The different chronograms evidence significant diurnal variations in water, sodium, potassium, urea, creatinine and proteins excretion of the two rodent urines. To compare easily the circadian variations in rat and mouse (with very marked differences in excretion intensities), the value of each urinary solute for each six-hour period is given as a percent of the total 24 hours excretion. 2. Daily excretion represents only 34 to 44% of the total 24 hour excretion. 3. These variations are exactly reproduced on the two consecutive days. 4. Chronogram drawings of the circadian variations of these six urinary solutes are very comparable in each rodent. 5. Moreover, these circadian variations in excretion are very similar, when compared in rat and mouse; the difference between homologous values in the two rodents is less than 2% in 2/3 of the cases.

Animals↗

[Diurnal variations evidence of glomerular filtration in the rat (author's transl)].

Parallel variations in plasma and urine variations of endogenous urea and creatinine level in the rat during 4 consecutive 6-h-long periods permit to evidence urea and creatinine clearance diurnal variations with very significant increase in the 2 nightly periods. The signification of this very large nightly glomerular filtration increase is discussed.

Animals↗

[Effect of the time of theophylline administration on the intensity of diuresis and natriuresis in the rat].

The present study originates in two experimental data: circadian variations evidence of water, electrolytes and solutes urinary excretion and theophylline diuretic and salidiuretic effects knowledge; we purpose to evidence theophylline-induced water and sodium renal excretion in rats as modified by the time of drug administration. Theophylline single dose is injected in 100 animals (20 lots of 5 rats) at 8 h, 14 h, 20 h or 2 h and urines are collected during a consecutive to injection hours long period: 8 h-14 h (I), 14 h-20 h (II), 20 h-2 h (III) or 2 h-8 h (IV). Diuresis increases in + 40,4 p. cent (I), in + 123,7 p. cent (II), in + 123,3 p. cent (III) in + 65,4 p. cent (IV). So, natriuresis increases in 39,6 p. cent (I), in 223,2 p. cent (II), in 114,3 p cent (III) and in 109,6 p. cent (IV). These results evidence that theophylline diuretic and natriuretic effects change strongly with injection time, being largest if it is injected at 14 h and slightest if injected at 8 h. Such observations prompt to study if the other pharmacological properties of theophylline, especially at pulmonary level, response also with a time-dependant intensity.

Animals↗

[Demonstration of the myotoxic effect of theophylline on the isolated kidney glomerulus of the rat].

After confirmation of the intense and very fast myorelaxant effect of theophylline on isolated glomeruli, xanthic reagent myotoxic effects are shown during more or less long contacts with these glomerular suspensions. We studied isolated glomeruli diameter evolution according to reagent dose (0,25 to 10 mg/ml) and its contact length (1, 5, 10 minutes). If the diameter remains practically constant during all the period for the lowest doses, it begins to decrease after the 5th minute for higher (1 and 2,5 mg/ml) and cracks up in the first minutes for the biggest ones (5 and 10 mg/ml). Pharmacologic and toxic actions are discussed ; hypothesis of a toxic effect at smooth muscular cells level is proposed.

Animals↗