Growth hormone regulates amino acid transport in human and rat liver.

Human growth hormone (GH) has been shown to improve nitrogen balance in surgical patients and to decrease urea production. This has been thought to be due primarily to an increase in protein synthesis in skeletal muscle. Little attention has focused on the liver as a possible site where GH may modulate amino acid uptake and thereby divert nitrogen away from urea-genesis. The authors hypothesized that GH regulates amino acid transport in hepatocytes at the plasma membrane level. They studied hepatic amino acid transport in 20 healthy surgical patients that received saline, low-dose GH (0.1 mg/kg/day), or high-dose (0.2 mg/kg/day) GH for 3 days before operation. At operation, a 5- to 10-g wedge biopsy of the liver was obtained, and hepatocyte plasma membrane vesicles were prepared by Percoll density gradient centrifugation. Vesicle transport of [3H]-MeAIB, a highly selective system A substrate, and [3H]-glutamine, a selective system N substrate, was measured, employing a rapid mixing/filtration technique. Hepatocyte plasma membrane vesicles were also prepared from 14 rats treated with saline or one of three different GH treatment regimens: (A) 12 hours after chronic GH treatment (6 mg/kg every 12 hours x 4 doses); (B) 4 hours after acute (1 dose) GH treatment; and (C) 4 hours after chronic GH treatment. In human liver vesicles, low-dose GH resulted in a 13% decrease in system A activity (p = not significant), whereas high-dose GH caused a marked 79% decrease (6.7 +/- 1.7 pmol/mg protein/10 seconds in control patients versus 1.4 +/- 0.7 in GH, p less than 0.05). System N was unaffected. Kinetic analysis of MeAIB transport by vesicles from high-dose GH patients showed the reduction in transport to be due to a 63% decrease in the Vmax (maximal transport velocity) with no alteration in the transport Km (carrier affinity). Vesicles from rats treated chronically with GH using a protocol similar to that used for human subjects exhibited decreased system A transport activity (10.4 +/- 0.4 pmol/mg pro/10 seconds in controls versus 7.5 +/- 0.2 in GH, p less than 0.05) secondary to a 59% reduction in the transport Vmax. Chronic growth hormone treatment decreases the activity of system A in both human and rat hepatocytes. This may be one mechanism by which GH diminishes hepatic urea-genesis and spares amino acids for peripheral protein synthesis.

Clinical and histological results of long-term management of aluminium overloading in uraemic patients with desferrioxamine.

Aluminium introxication in uraemic patients has been reported both in epidemic and sporadic forms. Desferrioxamine (DFO) results in strong Al mobilisation, but definitive treatment schedules, times of stop, and actual long-term Al removal her not been established. This study was carried out on three sporadic cases of Al intoxication treated with DFO for 3 1/2, 4 1/2 and 1 years. Clinical and laboratory parameters were employed to check the brain, bone and red cell status. Direct evaluation of Al kinetics showed that actual Al removal may be overestimated. In our experience it did not exceed 100 mg/year, and the ratio (DFO used/Al removed) decreased to 150 g/25 mg after two years of DFO, though considerable tissue deposits persisted in the patient who died after 3 1/2 years of treatment. Despite unexplained EEG worsening, neurological symptoms improved. Relapses, however, occurred after many years of DFO. Bone status improvement, at least in parathyroidectomised patients, proved to be only partial and time-related. The therapeutic effectiveness of DFO in these patients seemed to be exhausted after two years even if Al deposits had not vanished.

Hypervitaminosis B12 in maintenance hemodialysis patients receiving massive supplementation of vitamin B12.

We have administered routinely a multivitamin preparation containing a megadose of B12 to 106 hemodialysis patients after dialysis treatments. We found that these patients had very high levels of serum vitamin B12 which returned to original values only after a period of three years after stopping the vitamin. Discontinuing therapy had no effect on hemoglobin, mean erythrocyte corpuscular volume, or motor nerve conduction velocity. It is not known whether maintaining a prolonged high level of vitamin B12 is harmful. However, animal and epidemiologic studies have suggested that both cobalamin and cobalt may be potentially toxic. In view of the absence of demonstrable benefit and the possible risk of toxicity, we believe that the use of such megadose vitamin compounds in dialysis patients should be re-evaluated.

Three-year follow-up after withdrawal of iron therapy in uremic patients on regular dialytic treatment.

Iron supplementation is commonly recommended in uremic patients undergoing regular dialytic treatment in order to correct a presumed iron deficiency due to impaired absorption and dialytic losses. Serum ferritin levels show an iron overload in 83% of 136 patients on 1.25 g/year i.v. iron therapy. After the withdrawal of iron therapy, directly correlated ferritin levels and percentage transferrin saturation decreased slowly, except in carriers of HLA-A3 antigens and in polytransfused patients. In these latter patients, desferrioxamine reduced but did not normalize the iron balance. The 16 patients who never received iron therapy showed a normal iron balance over a 3-year follow-up. Despite iron-ferritin therapy, 11 patients with baseline ferritin values at the lower normal limits showed a tendency toward further depletion. Orally administered bivalent iron seems to be more promising in normalizing iron-deficient patients without potentially harmful overloading.