Increased Kidney Glucose Utilization Induced by Cyclosporine:Lack of Relation to Magnesium Excretion

Increased Kidney Glucose Utilization Induced by Cyclospone:Lack of Relation to Magnesium Excretion. BOROWITZ, J. L, MAYER,P. R., RODRIGUEZ, C A., AND ANTOUN, M. (1989).Fundam. Appl Toxicol12, 158–162. Cyclosporine enhances D-[5-³H]glucose utilizationin homogenates of rat kidney medulla but not kidney cortex orliver. This is true whether cyclosporine is added to fresh tissuehomogenates or is given to rats prior to sacrifice. Throughthe use of isolated perfused rat kidneys, an attempt was madeto relate increased glucose utilization by cyclosporine to apossible consequence of cyclosponne nephrotoxicity, viz., lossof magnesium in urine. Although an enhanced rate of glucoseutilization by cyclosporine was evident in isolated kidneys,glucose consumption was not related to urinary magnesium loss.In fact, kidneys from cyclosporine-treated rats actually showeda normal or even diminished urinary magnesium loss. The datasuggest that cyclosporine-induced magnesium imbalance may beextrarenal in origin and that the kidney medulla may be a primarysite of the nephrotoxic action of cyclosporine since the drugincreases glucose utilization at this site.     

THE REGROWTH OF RIGHT ATRIAL NORADRENERGIC NERVES AFTER 6-HYDROXYDOPAMINE IN GENETICALLY DIABETIC MICE: EFFECTS OF INSULIN TREATMENT

1 This study examined the rate of repletion of right atrial noradrenaline levels after a single dose (100 mg/kg i.p.) of 6-hydroxydopamine (6-OH Da) in diabetic and non-diabetic mice of the C57 BL/KS db/db strain. 2 In mice which received no 6-OH Da there was no significant difference, in endogenous noradrenaline levels, between diabetic and non-diabetic animals. The depletion of noradrenaline 24 h after 6-OHDa was slightly more profound in the diabetic mice than in non-diabetic controls. Thereafter the rate of repletion of noradrenaline was more rapid in the diabetic group. 3 The normal noradrenaline content was reinstated in diabetic mice between 7 and 10 days after 6-OHDa. In the non-diabetic group levels similar to those found in untreated mice were not reinstated until 14 days after 6-OHDa. 4 Ten days after 6-OHDa right atria from diabetic mice were markedly more responsive to stimulation of the intramural noradrenergic nerves than were preparations from non-diabetic mice. 5 A group of diabetic mice was treated with insulin (10 m Units/g daily) for 6 weeks. The right atria from these animals, examined 10 days after 6-OHDa, were similar in their responses to noradrenergic nerve stimulation to the preparations from the non-diabetic mice. 6 All these groups of atria gave similar responses to exogenous noradrenaline. These findings indicate that regrowth of noradrenergic terminals after 6-OHDa was more rapid in diabetic mice than in either insulin-treated diabetic mice or non-diabetic mice.     

Effect of sufentanil on intracranial pressure in neurosurgical patients

The effects of sufentanil on intracranial pressure, mean arterial pressure, cerebral perfusion pressure and heart rate were studied in 20 neurosurgical intensive care unit patients. Epidural intracranial pressure probes were implanted in patients who suffered head injury, intracerebral haemorrhage or underwent tumour resection. Sufentanil was given intravenously in sequential doses of 0.5, 1.0 and 2.0 micrograms/kg. Fifteen minutes elapsed after each dose. The patients were allocated to either group 1 (baseline intracranial pressure less than 20 mmHg) or group 2 (baseline intracranial pressure greater than 20 mmHg). Intracranial pressure did not change significantly in either group. Therefore the falls in mean arterial pressure with the highest dose in both groups and with 1.0 micrograms/kg in group 2, closely reflect corresponding reductions in cerebral perfusion pressure. As sufentanil in itself exerts no effects on intracranial pressure, concomitant haemodynamic changes are the critical factor for an adequate cerebral perfusion pressure.