Constituents of aromatic plants: carvacrol.

Carvacrol is a component of numerous aromatic plants. Up to now, no toxicological data were available. Carvacrol show a weak activity in the mutagenicity studies. Moreover, in the metabolism study, carvacrol has shown to be excreted with urine after 24 h in large quantities or unchanged or as glucoronide and sulphate conjugates. The available data do not allow the assessment of the NOEL. Further toxicological studies are needed.

Constituents of aromatic plants: elemicin.

No results of short-term or chronic toxicity studies have been found. Elemicin did induce UDS in hepatocytes from male rats. Studies on carcinogenicity were negative, but the 1'-hydroxy-metabolite of elemicin gave positive and negative results. The total intake of elemicin from essential oil seems to be limited. The main source of intake appears to be nutmeg. Further studies are needed to evaluate if the intake of elemicin may represent a health risk.

Constituents of aromatic plants: eucalyptol.

The subacute toxicity studies reported up to now in rats and mice suggested that mice were less susceptible than rats to the toxicity of eucalyptol. In fact, after gavage, it was found toxic in male rats at doses higher than 600 mg/kg while no effect was seen in mice up to 1200 mg/kg. However, the limitations and the quality of the study do not allow the extrapolation of a 'no effect level'. Several reports in rat and brushtail possum show the formation of hydroxylated bicycled products of eucalyptol as main metabolites. Moreover, metabolites which require ring opening have been also detected. Following the accidental exposure of human beings, death was reported in two cases after ingestion of 3.5-5 ml of essential eucalyptus oil, but a number of recoveries have also been described for much higher amounts of oil.

High- and low-flux acetate-free biofiltration: experimental assessment of calcium mass balance and intact parathyroid hormone behaviour.

We studied total calcium mass balance and plasma intact parathyroid hormone behaviour in 10 uraemic patients who underwent acetate-free biofiltration carried out in accordance with six different dialytic schedules, where either a polyacrylonitrile or a polysulphone membrane was used. Schedules 1 and 2 involved a reinfusion flow rate of 33.3 ml/min with a dialysate calcium concentration (DCa) of 1.75 and 2 mmol/l respectively; in schedule 3, 4, 5 and 6 reinfusion flow rate amounted to 50 ml/min and DCa was respectively of 1.75, 2, 2.25 and 2.5 mmol/l. Dehydration remained unchanged in all schedules: 700 g/h. Finally high- and low-flux acetate-free biofiltration are able to induce different Ca mass balance which may suit different therapeutic contexts. Ca mass balance was either positive or negative depending on reinfusion flow rate and DCa. With a reinfusion flow rate of 33.3 ml/min a DCa of at least 2 mmol/l was necessary to obtain a positive mass balance, while with a reinfusion flow rate of 50 ml/min DCa had to equal 2.25 mmol/l. In high-flux acetate-free biofiltration, the estimation of predialytic Ca2+ and DCa values, using a simple formula, allows prediction of the mass balance that will be attained. At the end of acetate-free biofiltration, intact parathyroid hormone always decreased when a polyacrylonitrile membrane was employed while it increased, in the presence of negative Ca mass balance with a polysulphone membrane.

Calcium mass balance and behavior of intact immunoreactive parathyroid hormone in acetate-free biofiltration: acute and one-year evaluation.

The present study evaluated calcium mass balance (MB) during acetate-free biofiltration (AFB) with a dialysate calcium concentration of 2 mmol/l and different ultrafiltration rates (UF; 42.5 ml/min in schedule 1 and 48.5 ml/min in schedule 3), and with a calcium concentration of 1.75 mmol/l but an UF of 43 ml/min (schedule 2). We also examined the effects of these schedules on the behavior of intact parathyroid hormone (I-PTH). AFB according to schedule 1 and 3 achieve a positive calcium MB (8.49 +/- 1.56 and 5.59 +/- 1.06 mmol, respectively), while in schedule 2 calcium MB merely balanced (0.07 +/- 2.29 mmol/l). A significant acute intradialytic I-PTH decrease was observed with all schedules; after 1 month, however, predialytic PTH values were unchanged in schedules 1 and 3, but worsening was noted in schedule 2. Subsequently, AFB was performed for 12 months employing a dialytic schedule (No. 1) involving a positive calcium balance. A year later I-PTH was significantly lower, thus proving that AFB may play an additional part in controlling secondary hyperparathyroidism.

Long-term effect of oral calcitriol single weekly pulse in CAPD and in HD.

This study was undertaken to evaluate the long-term effect of single weekly oral pulse calcitriol therapy (0.05 mcg/kg) in 16 uremic patients. Eight (5 female, 3 male; aged 51.6 +/- 8.5 years) were on continuous ambulatory peritoneal dialysis (CAPD) for 28.8 +/- 12.7 months with basal intact parathyroid hormone (iPTH) 247 +/- 60 pg/mL. Eight (6 female, 2 male; aged 53 +/- 17.9 years) were on hemodialysis (HD) for 76.3 +/- 55 months with basal iPTH 270.9 +/- 92. Calcium dialysate was 1.75 mmol/L in all patients and serum phosphorus was controlled with CaCO3 2-4 g/day. Ca and P were measured weekly; iPTH and alkaline phosphatase were measured monthly. After two months, iPTH decreased to 132.4 +/- 89 (p < 0.05 vs basal values) in the HD patients and to 158.2 +/- 61 (p < 0.05) in the CAPD group. After six months, iPTH decreased to 108.6 +/- 73.2 (p < 0.01) in the HD patients and to 126.5 +/- 48 (p < 0.01) in the CAPD patients. Two patients (1 HD and 1 CAPD) who were not compliant with phosphate binder therapy were dropped. To control hyperphosphatemia in 1 HD patient we reduced bolus to 0.03 mcg/kg. Two CAPD patients presented hypercalcemia and required calcium dialysate of 1.25 mmol/L. In conclusion, single weekly oral pulse of calcitriol appears to be effective in suppressing mild hyperparathyroidism both in CAPD and in HD patients, even though some variations in the protocols may be required.

Acute effects of repetitive hemodialysis on circulating immunoreactive parathyroid hormone levels in uremic patients undergoing vitamin D (calcitriol) therapy.

The acute effects on parathyroid gland activity of repetitive hemodialysis with a dialysate calcium concentration of between 3.5 and 4 mEq/l were evaluated in 21 hemodialysis patients on calcitriol therapy for 1 year or more. In this study circulating immunoreactive parathyroid hormone (iPTH) levels were measured using radioimmunoassay specific for C-terminal iPTH (C-PTH), middle molecule iPTH (MM-PTH) and intact iPTH (I-PTH), before the dialysis session at the end of the week (I), after 4 h regular hemodialysis (II) and after a further 72 h (III). C-PTH was abnormally high (202 +/- 64 pmol/l) (I) in 18 patients with no documented parathyroid hyperplasia and showed no significant difference in subsequent controls. MM-PTH was also high (379 +/- 125.5 pmol/l) (I), but decreased to 348 +/- 136.7 (II) (p less than 0.05) and returned to predialysis levels (III). I-PTH (I) was 8.2 +/- 5.3 pmol/l (normal levels in 8 patients), fell to 3.4 +/- 2.6 pmol/l (II) (p less than 0.01), and increased (p less than 0.01) with respect to the basal levels of 11.1 +/- 7.5 pmol/l (III). Three patients presented echographically documentable parathyroid hyperplasia and, despite constantly high iPTH levels, showed a similar I-PTH behavior while MM-PTH and C-PTH revealed no constant pattern. The decrease in iPTH levels was accompanied by a significant increase in total calcium and ionized calcium during the hemodialysis session. No significant changes in iCa and Ca together with I-PTH levels were found in 4 volunteers before and after the hemodialysis session with dialysate calcium 2.75 mEq/l. We conclude that I-PTH assay has been shown to capture acute changes in parathyroid gland activity in hemodialyzed patients for both low and high iPTH levels. High calcium dialysate hemodialysis inhibits acutely intradialytic PTH secretion but the effect is just temporary and the 72-hour interdialytic period, despite vitamin D therapy, stimulates parathyroid secretion significantly. Nevertheless, I-PTH fluctuations occur in some patients within the normal range, and high dialysate and calcitriol therapy seem to be capable of controlling parathyroid activity; as regards the remaining population, we suggest that a personalized therapeutic approach should be studied with a view to achieving a better control of interdialytic calcium homeostasis.