Aluminum inhibits hemoglobin synthesis but enhances iron uptake in Friend erythroleukemia cells

Aluminum (Al) overload in dialysis patients and experimental animals is associated with the development of anemia. However, the precise mechanisms of erythrocyte Al uptake and toxicity are poorly understood. Al accumulation, hemoglobin (Hb) synthesis and cell growth were evaluated in dimethylsulfoxide (DMSO)-induced Friend erythroleukemia cells (FEC), a model system for erythroid differentiation. FEC were grown in media containing either Al citrate, transferrin-aluminum (Tf-Al), Tf or no additions. Al accumulation occurring only in cells grown in Tf-Al containing media was detected at 24 hours and increased linearly up to 96 hours after induction. By 96 hours, 200 +/- 36 micrograms Al/liter lysed cells were detected in Tf-Al grown cells versus 5 +/- 1 micrograms Al/liter lysed cells in cells grown in Al citrate (P less than 0.001). Tf-Al inhibited Hb synthesis at 72 hours after induction. At 96 hours 50 +/- 15% cells were benzidine positive when grown in Tf-Al compared to 76 +/- 15% in Al citrate (P less than 0.001). FEC grown in increasing concentrations of Tf-Al (100 to 500 micrograms/ml) showed inhibition of Hb synthesis at lower concentrations of Tf-Al at 100 micrograms/ml than for cell growth at 300 micrograms/ml. Higher concentrations of Tf-Al (greater than 300 micrograms/ml) did not further inhibit Hb synthesis or cell growth. Iron (Fe) and Tf uptake were increased in Al loaded FEC compared to control cells. The increased Tf uptake was probably the result of increased Tf receptor expression on FES since Tf cell cycling time was unchanged. These data indicate that Al utilizes the Tf uptake pathway for entry into erythrocyte precursors. Al is toxic at sites distal to Fe uptake, possibly at the heme and/or globin synthetic pathways, resulting in decreased Hb synthesis and cell growth.     

Aluminum alters calcium influx and efflux from bone in vitro

Aluminum retention can cause osteomalacia and adynamic lesions of bone in patients undergoing long-term dialysis. It is not known, however, whether aluminum inhibits the mineralization of bone directly or whether alterations in osteoblastic function mediate this response. To examine this issue, the uptake of 45Ca by 14-day embryonic chick calvaria was measured in vitro. Comparative studies were done in living and devitalized tissues to evaluate the role of bone cells in aluminum-related changes in 45Ca uptake. Aluminum was added to serum-free media as the citrate complex, and paired hemicalvaria maintained in equimolar sodium citrate served as controls. Aluminum citrate decreased the uptake of 45Ca into bone during 24 hour incubations to 76 +/- 3% and 38 +/- 2% (x +/- SD) of control values at 10 microM and 100 microM aluminum, respectively. No change in 45Ca uptake was observed at the end of four hour incubations with 100 microM aluminum citrate, whereas 45Ca uptake decreased from 356 +/- 48 to 266 +/- 36 cpm/micrograms bone, P less than 0.05, at eight hours and from 327 +/- 22 to 269 +/- 41 cpm/micrograms bone, P less than 0.05, at 24 hours. The inhibitory effects of 10 microM and 100 microM aluminum on 45Ca uptake were eliminated, however, in devitalized tissues, and reductions in 45Ca uptake during incubations with aluminum were markedly attenuated by lowering the media phosphorus level from 4.0 mM to 2.0 mM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aluminum concentrations in serum, dialysate, urine and bone among patients undergoing continuous ambulatory peritoneal dialysis (CAPD)

Aluminum (Al) concentration in serum, urine, and dialysate was estimated in 21 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). In 12 of the patients bone Al concentration was measured as well. Mean serum Al level was 32.4 +/- 21.0 micrograms/l. The Al concentrations in the dialysate and urine were 9.1 +/- 4.1 micrograms/l and 52.5 +/- 47.3 micrograms/l, respectively. Bone Al concentration was 21.0 +/- 14.9 ppm and correlated significantly with concentrations of Al in serum (p less than 0.01) and dialysate (p less than 0.01). A mass transfer (MT) from the patients to the dialysate was observed in all patients (-44.0 +/- 28.8 micrograms/24 h). There was a highly significant correlation between peritoneal Al MT and serum Al (p less than 0.001), actual Al consumption (p less than 0.05) and bone Al concentration (p less than 0.005) supporting the existence of an overflow phenomenon. Despite very low Al levels in the dialysate, patients are at risk of elevated Al levels in the serum, dialysate, urine and bone because of consumption of Al-containing phosphate binders.     

Aluminium uptake by intestinal cells: effect of iron status and precomplexation.

The investigation of different aluminium-binding agents and metabolic conditions that might act as critical factors in modulating aluminium absorption could yield valuable information in the understanding of aluminium gastrointestinal absorption. We evaluated the effect of iron depletion in aluminium uptake and the role of transferrin and citrate in aluminium incorporation by the intestinal epithelial cell line RIE1. Both complex, aluminium-citrate and aluminium-transferrin were prepared in a molar ratio of 2:1; both facilitated the aluminium uptake although a greater aluminium incorporation was found when aluminium was administered as aluminium-transferrin. This difference became even greater in the iron-depleted cells (normal cells vs iron-depleted cells): 7.7 +/- 1.4 versus 30 +/- 5.6 ng Al/micrograms DNA (P less than 0.05). From these and previous data it is possible to speculate that iron status could modulate the intestinal uptake of aluminium and that both transferrin and citrate would act as effective carriers in the incorporation of aluminium into mucosal cells.     

Absorption and bioavailability of oral transmucosal fentanyl citrate.

Oral transmucosal fentanyl citrate (OTFC) is a novel, noninvasive dosage form of fentanyl used to provide children and adults with sedation, anxiolysis, and analgesia. In order to determine the bioavailability and absorption of fentanyl from OTFC, 12 volunteers were given intravenous fentanyl citrate or OTFC 15 micrograms/kg on each of two occasions. On a third occasion, the authors assessed oral administration (gastrointestinal absorption) by giving eight of the same volunteers the same dose of a solution of fentanyl citrate to swallow. In each study, arterial blood samples were taken over 24 h for analysis of plasma fentanyl. After intravenous (iv) administration of fentanyl, clearance (mean +/- standard deviation) was 0.67 +/- 0.15 l/min; volume of distribution at steady state was 287 +/- 79 l; and the terminal elimination half-life was 425 +/- 102 min. Peak plasma concentrations of fentanyl were higher (3.0 +/- 1.0 vs. 1.6 +/- 0.6 ng/ml, P = 0.01) and occurred sooner (22 +/- 2.5 vs. 101 +/- 48.8 min, P = 0.003) after OTFC than after oral solution administration. Plasma concentrations of fentanyl after OTFC decreased rapidly, to less than 1.0 ng/ml within 75-135 min after the beginning of administration. Peak absorption rate was greater (11.1 +/- 4.3 vs. 3.6 +/- 2.1 micrograms/min, P = 0.004) and occurred much sooner after OTFC than after oral solution administration (19 +/- 2.6 vs. 87.5 +/- 38.1 min, P = 0.001). Systemic bioavailability was greater after OTFC administration than after the oral solution (0.52 +/- 0.1 vs. 0.32 +/- 0.1, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

High deposition rate of aluminum in tissues in diabetic hemodialysis patients

Aluminum (Al) accumulation in bone is a serious problem in patients on hemodialysis. We studied deferoxamine infusion test (DFO test) in 14 diabetic patients on hemodialysis (HDDM) and 23 hemodialysis patients originated from glomerulo nephritis (HDCGN) to determine whether Al accumulation is different between the two groups or not. There was no difference in hemodialysis duration and total oral intake of Al containing drugs between two groups. Serum C-terminal parathyroid hormone (C-PTH) in HDDM was lower than that in HDCGN group (1.82 +/- 1.30 vs. 3.80 +/- 1.82 ng/ml; P less than 0.01). However serum Al (s-Al) levels were comparable (61.9 +/- 53.0 vs, 45.0 +/- 32.3 micrograms/l). A significant correlation was observed between duration of dialysis period and s-Al in HDDM (r = 0.806, p less than 0.01), but in HDCGN, the relation was not significant. The patients in HDDM whose cumulative aluminum intake was less than 2.0 kg showed the higher serum A1 concentrations before DFO and greater increases in s-Al after DFO test, as compared with those in HDCGN with matched aluminum intake (93.8 +/- 67.6 vs. 35.9 +/- 23.6 micrograms/l; p less than 0.001 and 141.2 +/- 81.8 vs. 70.3 +/- 41.1 micrograms/l; p = 0.035). These results indicate that in uremic diabetic patients with lower intake of Al containing drugs, an early accumulation of Al in the whole body occurs possibly because of the enhanced absorption rate of Al at an intestine and/or the low PTH level.     

Aluminium determination in the skin of patients with and without end-stage renal failure

Aluminium (Al) concentration in the skin was determined by inductively coupled plasma optical emission spectrometry to look for a correlation between Al exposure and skin content in patients with end-stage renal failure. Skin Al concentrations were higher in dialyzed patients than in the nondialyzed group (1.02 +/- 0.30 vs. 0.26 +/- 0.10 micrograms/g; p less than 0.001). Moreover, in the dialyzed group, the patients treated for more than 100 months had a higher concentration of Al in the skin than the others (1.20 +/- 0.26 vs. 0.80 +/- 0.18 micrograms/g; p less than 0.05). Al skin content correlated better with the deferoxamine infusion test (DIT) than with Al blood plasma concentration. In conclusion, our data confirm that the DIT is a valuable tool for the evaluation of body Al content.     

Ascorbic acid does not augment the restoration effect of iron treatment for empty iron stores in patients after gastrointestinal surgery

The effect of a 6-week combined treatment with ferrous sulfate (80 mg Fe++ three times daily) and ascorbic acid (75 mg three times daily) on the empty iron stores in 20 patients after gastrointestinal surgery was examined from changes of serum ferritin. One group of 20 patients with similar clinical characteristics served as controls. The treatment replaced the empty iron stores. Since mean serum ferritin concentrations increased from 9 +/- 8 to 29 +/- 11 micrograms/l (P less than 0.001) in males and from 8 +/- 8 to 26 +/- 10 micrograms/l (P less than 0.001) in the females. Also blood hemoglobin and serum iron concentrations increased significantly (P less than 0.01). Among the controls there were no marked changes in serum ferritin, blood hemoglobin or serum iron concentrations. However, the increase of serum ferritin caused by this combined treatment was similar with that caused previously by pure ferrous sulfate treatment. Thus, it is considered that the combined treatment with ferrous sulfate (80 mg Fe++ three times daily) and ascorbic acid (75 mg three times daily) restores the empty iron stores in patients after gastrointestinal surgery, but that the increase is not augmented by the ascorbic acid. Thus, a pure iron therapy is recommended to fill up the empty iron stores in these patients.     

Effects of deferoxamine, feroxamine and iron on experimental mucormycosis (zygomycosis)

Mucormycosis was induced in healthy guinea pigs by the i.v. injection of spores from Rhizopus microsporus var. rhizopodiformis or from Rhizopus oryzae, leading to a reproducible mortality. Pretreatment with one dose of 50 mg of deferoxamine (DFO) shortened animal survival from 4.2 +/- 0.4 to 3.3 +/- 0.5 days for Rh. rhizopodiformis and from 8.8 +/- 0.4 to 7.3 +/- 1.9 days for Rh. oryzae (P less than 0.05). Survival was shortened even more after 4 doses of DFO (P = 0.0013 for Rh. rhizopodiformis and P = 0.002 for Rh. oryzae). After Rh. oryzae infection, animal survival decreased similarly after DFO, feroxamine or DFO combined with Fe3+ citrate (P less than 0.001). Fe3+ citrate also decreased survival (P = 0.0011), although significantly less than DFO either alone or combined with Fe3+. In vitro growth of both fungal strains was enhanced by addition of either DFO or Fe3+ at 0.001 to 1 mmol in the medium. DFO abolished the prolonged survival induced by amphotericin B in vivo and in vitro. Indeed, four doses of DFO abolished the improved survival due to amphotericin B (P = 0.0019 for Rh. rhizopodiformis and P = 0.002 for Rh. oryzae); DFO combined with Fe3+ at greater than or equal to 0.1 mmol decreased the antifungal activity of amphotericin B in vitro. These results point to a major role of DFO in the pathogenesis of mucormycosis in dialysis patients and suggest that DFO behaves as a siderophore for Rhizopus strains, stimulating their growth.     

Seminal lead and copper in fertile and infertile men: Blei und Kupfer im Spermaplasma bei fertilen und infertilen Männern

Lead and copper concentrations were determined by atomic absorption spectroscopy in semen from 18 fertile and 172 infertile men. Significant correlations between copper concentrations in semen and sperm concentration (r = 0.32, P less than 0.001), percentage progressive motility (r = 0.23, P less than 0.005) and normal morphology (r = 0.22, P less than 0.005) were observed, while no such correlation existed for lead. However, semen copper concentrations of infertile men (194.99 +/- 5.70 micrograms l-1) and fertile men (183.39 +/- 14.37 micrograms l-1) did not differ significantly. Mean lead concentration in semen of fertile men was 11.18 +/- 0.62 micrograms l-1 and significantly higher than lead concentration in semen of fertile men (5.61 +/- 0.53 micrograms l-1, P less than 0.006). Reinvestigation of 18 infertile men after 2 years showed a significant drop of lead concentrations in semen from 17.31 +/- 1.41 to 6.94 +/- 1.32 micrograms l-1 (P less than 0.0002), which might be related to the decreasing use of leaded petrol in the Federal Republic of Germany.     

Light chain effects on alanine and glucose uptake by renal brush border membranes

Effect of varying concentrations (0 to 800 microM) of three different light chains on sodium-dependent L-(14C)alanine and D-(14C)glucose uptake by rat renal brush border membrane vesicles were studied. One kappa and two lambda type light chains (lambda-1 and lambda-2) were isolated from urines of patients with multiple myeloma. At maximal inhibitory concentrations the kappa chain reduced alanine uptake from 206 +/- 18 to 77 +/- 18 pmole/mg protein (P less than 0.005) and glucose uptake from 357 +/- 22 to 146 +/- 8 pmole/mg protein (P less than 0.001). lambda-1 reduced alanine uptake from 136 +/- 17 to 60 +/- 8 pmole/mg protein (P less than 0.005) and glucose uptake from 354 +/- 17 to 77 +/- 14 pmole/mg protein (P less than 0.001). lambda-2 reduced alanine uptake from 105 +/- 9 to 28 +/- 5 pmole/mg protein (P less than 0.001) and glucose uptake from 194 +/- 7 to 66 +/- 7 pmole/mg protein (P less than 0.001). The half maximal inhibitory concentrations (I50) of kappa, lambda-1 and lambda-2 light chains were 68, 76 and 140 microM for alanine uptake and 120, 70 and 105 microM for glucose uptake. Control experiments using bovine serum albumin and beta-lactoglobulin showed no inhibitory effect on alanine and glucose uptake by either protein. These data reveal brush border membrane effects by myeloma light chains and confirm that direct Bence Jones protein nephrotoxicity may play an important role in the pathogenesis of kidney dysfunction associated with multiple myeloma.     

Acute phosphate depletion and in vitro rat proximal tubule injury: protection by glycine and acidosis.

The effects of phosphate (PO4) removal from Krebs Henseleit buffer on freshly isolated rat proximal tubules (rPT) were assessed by measuring Ca2+ uptake (nmol/mg protein), cellular adenosine triphosphate (ATP) (nmol/mg), tissue K+ content (nmol/mg) and lactate dehydrogenase (LDH) as an index of cell integrity. Ca2+ uptake increased by 50% in rPT incubated in zero PO4 medium as compared to control (2.6 +/- 0.1 vs. 3.9 +/- 0.19, P less than 0.001) and LDH release increased 2.5-fold from 14.2 +/- 0.6 to 31.6 +/- 1.6%, P less than 0.001. Neither verapamil (200 microM) nor mepacrine (50 microM) reduced Ca2+ uptake or decreased LDH release suggesting that the increased Ca2+ uptake was not occurring through potential operated channels and that phospholipase-induced cell injury was not the cause of increased LDH release. Either glycine (2 mM) or extracellular fluid acidosis (pH 7.06), however, significantly diminished rPT injury and Ca2+ uptake. Specifically, as compared to the increased LDH released in untreated. PO4-depleted rPT, LDH release was diminished significantly by glycine treatment (31.0 +/- 0.9 vs. 15.5 +/- 1.6%, P less than 0.001) or acidosis (30.3 +/- 0.04 vs. 19.2 +/- 0.9%, P less than 0.01). Ca2+ uptake did not increase in glycine treated tubules (2.6 +/- 0.1 vs. 2.8 +/- 0.2 nmol/mg, NS) or in the presence of acidosis (2.6 +/- 0.1 vs. 2.97 +/- 0.17 nmol/mg, NS). ATP concentrations were markedly reduced by PO4 depletion (2.8 +/- 0.2 vs. 4.8 +/- 0.3 nmol/mg, P less than 0.001) and remained at low levels during either acidosis or glycine-induced protection.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vitro cyclosporine toxicity. The effect of verapamil

The epithelial cell line LLC-PK1, which expresses many proximal tubular characteristics, was used to investigate the relationship between calcium, the calcium channel blocker verapamil, and cyclosporine toxicity. The LLC-PK1 cells took up cyclosporine when this was added in a concentration of 2 micrograms/ml, and this uptake was maximal at 30 min (112 +/- 3 ng cyclosporine/mg cell protein). At 12 micrograms/ml it inhibited the sodium glucose cotransporter, as assessed by phlorizin-inhibitable 14C-alpha-methyl glucopyranoside (alpha-MG) uptake (control 37.2 +/- 6.3, 12 micrograms/ml 21.2 +/- 1.1 mumol/hr/mg protein). Cyclosporine at 2 micrograms/ml did not affect cell growth after 5 days (control 945 +/- 60 micrograms cell protein per 25 cm2 flask, 2 micrograms/ml cyclosporine/ml 1046 +/- 32 micrograms protein/flask), even in the presence of 7.6 mM ionized calcium (862 +/- 37 micrograms protein/flask). Cyclosporine at 12 micrograms/ml inhibited cell growth (286 +/- 27 micrograms protein/flask), and raising the ambient ionized calcium concentration to 7.6 mM reduced cell growth further (91 +/- 6 micrograms protein/flask). Cyclosporine at concentrations of 2 and 12 micrograms/ml produced increasing cell vacuolation, as seen in vivo. Short-term uptake of 2 micrograms/ml cyclosporine could be inhibited by 1.0 mM and 0.5 mM verapamil (49 +/- 9.5 and 71 +/- 6.4 ng cyclosporine/mg cell protein, respectively, at 30 min). However, in the presence of 2 micrograms/ml cyclosporine 0.1 mM verapamil was toxic to the cells grown over five days (44 +/- 5 micrograms protein/flask). At 0.01 mM verapamil was not toxic to cell growth (921 +/- 29 micrograms protein/flask), but raising the medium calcium to 7.6 mM reduced cell growth (652 +/- 96 micrograms/ml). Inhibition of cyclosporine uptake did not occur with 0.01 mm verapamil (control 145.6 +/- 12.3 vs. 0.01 mM verapamil 150.4 +/- 3.8 ng cyclosporine/mg cell protein). The LLC-PK1 cell line represents a good in vitro model for cyclosporine renal tubular toxicity, as the in vivo observation of glycosuria and proximal tubular cell vacuolation in cyclosporine nephrotoxicity can be reproduced. In vitro this is shown to be associated with inhibition of sodium-dependent glucose cotransport. Verapamil inhibited cyclosporine uptake, but only at concentrations that were toxic to the cells. Verapamil potentiated rather than reduced the increased cyclosporine toxicity produced by increasing the medium calcium concentration. The suggested protective effect of verapamil against cyclosporine nephrotoxicity is therefore unlikely to be due to inhibition of cyclosporine uptake or of calcium entry into proximal tubular cells.     

Residual renal function in hemodialysis patients may protect against hyperaluminemia

We investigated 106 home hemodialysis patients whose mean [+/- SEM] serum aluminum (Al) concentration was 60.9 +/- 4.1 micrograms/liter. Serum Al concentration was inversely related to daily urine output (r = -0.52, P less than 0.001). Urine volume and measurements of Al exposure were included in a multivariate analysis of serum Al concentration in the 62 patients whose urine output was greater than 10 ml/day. The multiple correlation coefficient (r) was 0.70 (P less than 0.001) and the percentage contributions to r2 (indicating the relative importance of each factor) were: urine output 57%, oral Al intake 36%, total dialysis hours 7%. The additional contribution from cumulative water Al was negligible. In a subgroup of 26 patients with a urine output exceeding 10 ml/day, urinary Al excretion averaged 15.4 micrograms/day, and renal Al clearance and serum Al concentration were inversely related (r = -0.69, P less than 0.001). We conclude that Al-containing phosphate binders were a more important source of Al than was dialysate in these patients and that residual renal function can reduce the severity of hyperaluminemia in hemodialysis patients.     

Urinary and renal tissue kallikrein in the streptozocin-diabetic rat

The renal kallikrein-kinin system is thought to participate in blood pressure regulation and displays abnormalities in human hypertension, as well as in many animal models of hypertension. Urinary excretion and tissue levels of renal kallikrein were measured in streptozocin (STZ)-diabetic rats in relation to blood pressure, glycemia, and insulin treatment. In study 1, STZ-diabetic rats with marked hyperglycemia showed reduced kallikrein-like esterase excretion, compared with control rats, when first measured after 7 days of diabetes (9.9 +/- 2.5 versus 17.5 +/- 2.4 EU/24 h, P less than 0.05). This difference increased with time and, after 210 days, urinary esterase excretion in diabetic and control rats was 6.7 +/- 2.1 and 39.0 +/- 6.0 EU/24 h, respectively (P less than 0.001). Urine kallikrein, measured by radioimmunoassay, was similarly reduced in diabetic rats (40.4 +/- 8.0 versus 88.0 +/- 6.5 micrograms/24 h, at 30 days, P less than 0.001). At 120 days, systolic blood pressures were elevated in diabetic rats (P less than 0.05), and at 180 days over 60% of the diabetic rats had pressures above the highest pressures of control rats. In study 2, STZ-diabetic rats were treated with insulin for 2 wk (2 U NPH at 0800 h, or 2 U NPH at 0800 and 1600 h). In the single-dose group, with hyperglycemia similar to that of diabetic rats in study 1, kallikrein excretion was reduced as early as day 2, compared with nondiabetic rats (56.0 +/- 6.1 versus 109 +/- 9.4 micrograms/24 h, respectively, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Development of rat embryos cultured in glucose-deficient media

Embryo-culture techniques were used to study the effects of exposure to glucose-deficient culture media on rat embryos during organogenesis. Embryos and their extraembryonic membranes (explants) were cultured either in control media or in media with low or very low glucose concentrations. At the start of the culture the glucose concentrations were 8.4 +/- 0.57, 4.5 +/- 0.10, and 3.5 +/- 0.07 mM. During the cultures, the explants progressively depleted the glucose in the medium until, after 48 h, the glucose concentrations were reduced to 1.1 +/- 0.18, 0.4 +/- 0.13, and 0.3 +/- 0.02 mM, respectively. At glucose concentrations less than 2.5 mM, the rate of glucose uptake by the explants progressively decreased, and embryonic growth and differentiation became increasingly retarded. After 48 h in glucose-deficient culture media, embryos had smaller crown-rump lengths, lower protein contents, and fewer somites than embryos from the control media (P less than .001). Most of the embryos exposed to the lower glucose concentrations also had severe dysmorphic lesions, especially of the head and branchial arches. The deleterious effects of exposure to low concentrations of glucose on embryonic development appeared not to be reversible. Embryos cultured for 24 h in media with a low concentration of glucose followed by 24 h in control medium grew and developed just as poorly as those cultured for the entire 48 h in the glucose-deficient media.     

Plasma and red blood cell cyanide concentrations during hypotension induced by sodium nitroprusside or by a nitroprusside-trimetaphan mixture in rabbits

Plasma and red blood cells cyanide concentrations during hypotension induced by sodium nitroprusside and a nitroprusside-trimetaphan mixture were studied in 29 male rabbits under halothane anesthesia. They were randomly divided into three groups; Nitroprusside (group N; n = 10), A nitroprusside-trimetaphan mixture (group M; n = 10), Controls (group C; n = 9). No changes were noted in plasma and red blood cells cyanide concentrations in group C throughout the experiment. During and after induced hypotension, in group N, plasma cyanide concentration was significantly higher than the control value. The maximum increase occurred 60min after induction of hypotension and the highest concentration of plasma cyanide was six times the control value. In contrast, in group M, plasma cyanide concentration was unchanged from the control value. However, during and after induced hypotension, red blood cells cyanide concentrations of group N and group M were significantly higher compared with the control values. Red blood cells concentrations of cyanide increased for 30 and 60 min during induced hypotension in group N (27.11 +/- 3.9 micrograms.ml-1, P less than 0.001, 46, 73 +/- 4.7 micrograms.ml-1, P less than 0.001, respectively) and in group M (0.31 +/- 0.05 micrograms.ml-1, P less than 0.05, 0.29 +/- 0.03 micrograms.ml-1, P less than 0.05, respectively). In conclusion, the data suggest that a nitroprusside-trimetaphan mixture is a safe method for hypotensive anesthesia.     

Concomitant iron and aluminum mass transfer following deferoxamine infusion during hemofiltration

Variable tissue overloading can alter the removal rate of iron and aluminum from uremics. Owing to its higher affinity to deferoxamine (DFO) and higher plasma concentrations, Fe could impair Al removal in cases of simultaneous body burden. Fe and Al plasma kinetics and mass transfer were therefore studied in 12 uremic patients with different Fe and Al status: six with normal ferritin levels (less than 400 micrograms/L [ng/mL]), and Al 1.4 to 4.7 mumol/L (40 to 131 micrograms/L) (group A); six with increased ferritin (greater than 2,000 micrograms/L), and Al 1.7 to 17 mumol/L (47 to 476 micrograms/L) (group B). DFO (40 and 80 mg/kg in a random sequence) was administered once a week during the first hour of the first hemofiltration (HF). The results show that in both groups and with both DFO doses, maximum Fe and Al mass transfer was achieved in the first and second HF, respectively. The 80-mg/kg dose of DFO significantly raised Al mass transfer in both groups, whereas Fe mass transfer was only slightly affected. Even though plasma Fe levels were almost always higher than Al, Al mass transfer eventually exceeded that of Fe, in both Fe-normal and Fe-overload patients. The bias towards Al in mass transfer was enhanced in both groups in the second HF, and at the higher DFO doses. Thus, DFO once a week reduced Fe loss to less than 30 mumol/wk in patients with normal ferritin levels. In both Fe and Al overloaded patients, Al can be removed, and Al mass transfer may often exceed Fe mass transfer, depending on the degree of tissue burden, the time from DFO infusion, and the DFO dose.     

Continuous interpleural infusion of bupivacaine for postoperative analgesia after surgery with flank incisions: a double-blind comparison of 0.25% and 0.5% solutions.

Postoperative analgesia, as assessed by visual analogue scale scores (0-10) and patient-controlled analgesia morphine requirements, pulmonary function (forced vital capacity and forced expiratory volume in 1 s), and plasma bupivacaine concentrations were studied in patients receiving interpleural blockade with bupivacaine after surgery with a flank incision. Two groups of 10 patients received either 0.5% or 0.25% bupivacaine, both with epinephrine (5 micrograms/mL). Pain relief was initiated when patients had visual analogue scale scores greater than or equal to 4. Patients received 21 mL of bupivacaine 0.25% or 0.5% in a double-blind fashion. One hour later, a continuous infusion of 5 mL/h of the study solution was started. At the same time, patient-controlled analgesia became accessible to the patients. The onset time of pain relief and the area under the visual analogue scale score-time curves over the first 8 h were similar in both groups. Patient-controlled analgesia morphine use was also similar in the 0.25% (21.3 +/- 14.6 mg) and 0.5% (21.0 +/- 16.0 mg) groups (mean +/- SD). In both groups, forced vital capacity and forced expiratory volume in 1 s improved significantly within 60 min (P less than 0.05). Peak plasma concentrations (Cmax) and the area under the plasma concentration-time curve (AUC) over 24 h were higher (P less than 0.001) in the 0.5% group (Cmax, 1.47 +/- 0.37 micrograms/mL; AUC, 1511 +/- 323 micrograms.mL-1.min) than those in the 0.25% group (Cmax, 0.55 +/- 0.22 micrograms/mL; AUC, 680 +/- 118 micrograms.mL-1.min) (mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS)     

Increase of body iron stores estimated by the increase of serum ferritin concentration during a treatment of 200 mg Fe++ daily after gastrointestinal surgery

A 6-week iron therapy of 200 mg Fe++ daily was given to 13 men and 12 women who had previously undergone various kinds of common gastrointestinal surgery and who had empty iron stores estimated from low serum ferritin concentration. The results were compared with those of a control group corresponding to the study group in respect of sex, number of patients, primary disease, previous operation, empty iron stores (serum ferritin), blood hemoglobin, serum iron, sedimentation rate, blood leukocytes, serum transferrin, folate and vitamin B12. The iron therapy restored the lack of body iron, for the serum ferritin concentrations increased from 12 +/- 7 to 30 +/- 11 micrograms/l (p less than 0.001) in the men and from 10 +/- 6 to 30 +/- 12 micrograms/l (p less than 0.001) in the women, whereas the corresponding changes in the control group were from 10 +/- 9 to 11 +/- 8 micrograms/l and from 11 +/- 8 to 13 +/- 11 micrograms/l in the men and women, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)