Determination of iron, copper, zinc, magnesium and selenium in plasma and erythrocytes in neurosurgical patients.

A direct method for determination of Fe, Cu, Zn, Mg and Se in erythrocytes was developed. The aim of the present study was to establish a method for examining perioperative levels of the above mentioned elements simultaneously in erythrocytes and plasma by atomic absorption spectrophotometry in 11 patients undergoing neurosurgery for acute spinal nerve compressions because of intervertebral disk prolapses. Reference values for erythrocytes were 11.49 +/- 3.48 mmol/mmol Hb; 0.82 +/- 0.087 mmol/mmol Hb; 9.01 +/- 2.20 mmol/mmol Hb; 0.104 +/- 0.032 mmol/mmol Hb; 0.07 +/- 0.050 mmol/mmol Hb for iron, copper, zinc, magnesium, and selenium, respectively. Postoperative erythrocyte concentrations did not differ significantly compared to those obtained preoperatively and remained within the reference ranges perioperatively. For plasma the following reference values were used: 19.0 +/- 8.0 mmol/l (Fe); 20.1 +/- 8.2 mmol/l (Cu); 15.4 +/- 4.6 mmol/l (Zn); 0.9 +/- 0.15 mmol/l (Mg); 1.02 +/- 0.3 mmol/l (Se). There was a significant decrease in the concentration of copper in plasma (13.41 +/- 3.46 mmol/l, p < 0.1) and zinc (10.73 +/- 2.73 mmol/l, p < 0.1) immediately postoperative, iron (10.56 +/- 3.91 mmol/l, p < 0.1) and zinc on day 1 (11.28 +/- 1.88 mmol/l, p < 0.10), and a significant postoperative increase of copper on day 5 (18.81 +/- 3.97 mmol/l, p < 0.1), postoperatively. The mean plasma concentrations of iron, copper, zinc magnesium and selenium remained within the reference ranges during the entire period.     

Haemoglobin levels according to age, haematocrit, transferrin and serum iron level in medical students of comparable socio-economic status.

1. The haemoglobin, haematocrit, transferrin and serum iron of a group of 418 healthy medical students, aging from 18 till 25 years, were determined. The mean Hb for the male students was 9.4 +/- 0.63 mmol/l, for the female students 8.7 +/- 0.56 mmol/l. 2. The correlations between Hb, Ht, SeFe and transferrin have been investigated. A positive correlation exists between Hb and SeFe and Ht and SeFe.     

Quantitative analysis of serum sodium concentration after prolonged running in the heat.

This study compared measured serum [Na(+)] (S([Na+]); brackets denote concentration) with that predicted by the Nguyen-Kurtz equation after manipulating ingested [Na(+)] and changes in body mass (DeltaBM) during prolonged running in the heat. Athletes (4 men, 4 women; 22-36 yr) ran for 2 h, followed by a run to exhaustion and 1-h recovery. During exercise and recovery, subjects drank a 6% carbohydrate solution without Na(+) (Na(+)0), 6% carbohydrate solution with 18 mmol/l Na(+) (Na(+)18), or 6% carbohydrate solution with 30 mmol/l Na(+) (Na(+)30) to maintain BM (0%DeltaBM), increase BM by 2%, or decrease BM by 2% or 4% in 12 separate trials. Net fluid, Na(+), and K(+) balance were measured to calculate the Nguyen-Kurtz predicted S([Na+]) for each trial. For all beverages, predicted and measured S([Na+]) were not significantly different during the 0%, -2%, and -4%DeltaBM trials (-0.2 +/- 0.2 mmol/l) but were significantly different during the +2%DeltaBM trials (-2.6 +/- 0.5 mmol/l). Overall, Na(+) consumption attenuated the decline in S([Na+]) (-2.0 +/- 0.5, -0.9 +/- 0.5, -0.5 +/- 0.5 mmol/l from pre- to postexperiment of the 0%DeltaBM trials for Na(+)30, Na(+)18, and Na(+)0, respectively) but the differences among beverages were not statistically significant. Beverage [Na(+)] did not affect performance; however, time to exhaustion was significantly shorter during the -4% (8 +/- 3 min) and -2% (14 +/- 3 min) vs. 0% (22 +/- 5 min) and +2% (26 +/- 6 min) DeltaBM trials. In conclusion, when athletes maintain or lose BM, changes in S([Na+]) can be accurately predicted by changes in the mass balance of fluid, Na(+), and K(+) during prolonged running in the heat.     

Effect of short-term testosterone treatment on leptin concentrations in boys with pubertal delay

Testosterone administration increases growth hormone (GH) secretion and decreases the plasma leptin concentration in men. We evaluated the effect of increased GH secretion due to short-term testosterone treatment on leptin concentrations. Ten boys aged 14.8 +/- 0.2 (mean +/- SE) years with transient GH deficiency caused by pubertal delay were evaluated before and after (3 months) 4 intramuscular injections of 100 mg testosterone heptylate, given at 15-day intervals. The leptin concentration decreased from 5.4 +/- 1.3 to 3. 6 +/- 1.1 microgram/l (p < 0.001), despite a weight gain of 3.4 +/- 0.5 kg. There were significant increases in body mass index (BMI), from -0.2 +/- 0.5 to 0.2 +/- 0.5 SD, p < 0.005, in GH peak after stimulation test, from 6.3 +/- 0.5 to 21.7 +/- 2.9 microgram/l, p < 0. 0003, in plasma testosterone, from 0.6 +/- 0.1 to 6.5 +/- 1.3 microgram/l, p < 0.001, in insulin-like growth factor-I (IGF-I), from 152 +/- 21 to 330 +/- 30 microgram/l, p < 0.0001, and in IGF-binding protein-3 (IGFBP-3), from 4.2 +/- 0.5 to 5.4 +/- 0.4 mg/l, p < 0.01. But there were no changes in blood glucose (4.7 +/- 0.1 and 4.8 +/- 0.1 mmol/l), or plasma fasting insulin (9.0 +/- 1.2 and 8.1 +/- 1.3 mIU/l). The leptin concentrations were positively correlated with the BMI before (p < 0.03) and after (p < 0.04) testosterone, but not with the GH peak after stimulation, or with plasma testosterone, IGF-I or IGFBP-3. The leptin and insulin concentrations after testosterone treatment were positively correlated (p < 0.04). Thus, short-term testosterone treatment of boys with pubertal delay decreases their leptin concentrations. The lack of correlation with GH secretion or with its changes, despite the dramatic increase in GH secretion, and the lack of change in insulin are additional features suggesting that testosterone increases the leptin concentration mainly by an effect on adipose tissue.     

Impact of human growth hormone on plasma lipoprotein concentrations

To evaluate whether the moderately elevated human growth hormone concentration, seen in insulin dependent diabetic patients, has any impact on lipoproteins, human growth hormone was given to nondiabetic persons in doses which would bring their plasma human growth hormone concentration up in the same level as seen in insulin dependent diabetic patients. After one week of treatment with human growth hormone we found total plasma triglyceride to be significantly raised (0.98 mmol/l +/- 0.28 mmol/l (mean +/- SD) before versus 1.27 mmol/l +/- 0.38 mmol/l (mean +/- SD) after treatment). Very low density lipoprotein (VLDL) was separated into two fractions (VLDL-1 and VLDL-2) of which VLDL-2 is regarded as a VLDL-remnant which is suggested to be of importance for development of atherosclerosis. After one week of human growth hormone treatment there were no changes in VLDL-1 concentrations whereas a significant raise in VLDL-2 triglyceride and VLDL-2 cholesterol was seen.     

Adaptive responses during anemia and its correction in lambs.

There is limited information available on which to base decisions regarding red blood cell (RBC) transfusion treatment in anemic newborn infants. Using a conscious newborn lamb model of progressive anemia, we sought to identify accessible metabolic and cardiovascular measures of hypoxia that might provide guidance in the management of anemic infants. We hypothesized that severe phlebotomy-induced isovolemic anemia and its reversal after RBC transfusion result in a defined pattern of adaptive responses. Anemia was produced over 2 days by serial phlebotomy (with plasma replacement) to Hb levels of 30-40 g/l. During the ensuing 2 days, Hb was restored to pretransfusion baseline levels by repeated RBC transfusion. Area-under-the-curve methodology was utilized for defining the Hb level at which individual study variables demonstrated significant change. Significant reciprocal changes (P < 0.05) of equivalent magnitude were observed during the phlebotomy and transfusion phases for cardiac output, plasma erythropoietin (Epo) concentration, oxygen extraction ratio, oxygen delivery, venous oxygen saturation, and blood lactate concentration. No significant change was observed in resting oxygen consumption. Cardiac output and plasma Epo concentration increased at Hb levels <75 g/l, oxygen delivery and oxygen extraction ratio decreased at Hb levels <60 g/l, and venous oxygen saturation decreased and blood lactate concentration increased at Hb levels <55 g/l. We speculate that plasma Epo and blood lactate concentrations may be useful measures of clinically significant anemia in infants and may indicate when an infant might benefit from a RBC transfusion.     

Threat of unemployment and cardiovascular risk factors: longitudinal study of quality of sleep and serum cholesterol concentrations in men threatened with redundancy.

OBJECTIVE--To assess whether the threat of unemployment affects risk factors for cardiovascular disease. DESIGN--Longitudinal study of a cohort of middle aged shipyard workers followed up for a mean of 6.2 (SD 1.9) years and a group of controls observed for the same period. The first investigation took place during a period of relative economic stability for the shipyard and the second during the phase of its closure. SETTING--An age cohort health screening programme in Malmö, Sweden. PARTICIPANTS--715 Male shipyard workers and 261 age matched male controls. MAIN OUTCOME MEASURES--Changes in 19 variables related to the risk of cardiovascular disease, and psychological variables, alcohol consumption, smoking, and dietary habits as assessed by questionnaire. RESULTS--Serum cholesterol concentrations increased more (mean 0.25 (SD 0.68) mmol/l v 0.08 (0.66) mmol/l) and serum calcium concentrations decreased less (-0.06 (0.10) mmol/l v -0.08 (0.09) mmol/l) in the shipyard workers than in the controls. A correlation was found between scores for sleep disturbance and changes in serum cholesterol concentration. In the whole series there was a greater increase in serum cholesterol concentrations among men threatened with unemployment (437/976; 44.8%) than among those who were not. In stepwise regression analysis the change in serum cholesterol concentration was correlated with changes in haemoglobin concentration, body weight, and serum triglyceride and calcium concentrations. A positive correlation was found between change in cholesterol concentration and change in blood pressure, indicating that the overall risk profile had worsened among men with increased serum cholesterol concentrations. CONCLUSIONS--Risk of unemployment increases the serum cholesterol concentration in middle aged men, the increase being more pronounced in those with sleep disturbance. The increase in serum cholesterol is related to changes in other established risk factors for cardiovascular disease. These findings might partly explain the excessive mortality due to cardiovascular disease recorded among the unemployed and people with sleep disturbance.     

Galanin in the porcine pancreas.

Galanin, a 29 amino acid neuropeptide, was recently isolated from pig intestine. We studied the localization, nature and effect of galanin in pig pancreas. Galanin immunoreactive nerve fibers were regularly found in the pancreas. A peptide chromatographically similar to synthetic galanin was identified in pancreas extracts. The effect of galanin on the endocrine and exocrine secretion was studied in isolated pancreases, perfused with a synthetic medium containing 3.5, 5 or 8 mmol/l glucose and synthetic galanin (10(-10)-10(-8) mol/l). There was no effect on the basal exocrine secretion. The output of insulin, glucagon, somatostatin and pancreatic polypeptide (PP) was measured in the effluent. There was no effect on PP secretion. At a perfusate glucose concentration of 5 mmol/l, galanin at 10(-9) mol/l increased insulin secretion by 55 +/- 14% (mean +/- S.E.M., n = 5) of basal secretion, and at 10(-8) mol/l by 58 +/- 27% (n = 6). At 8 mmol/l glucose, insulin secretion increased by 25 +/- 10% (n = 6) and 62 +/- 17% (n = 8). At 5 mmol/l glucose glucagon secretion was increased by 15 +/- 3% (n = 5) by galanin at 10(-9) mol/l and by 29 +/- 11% (n = 5) by galanin at 10(-8) mol/l, and at 8 mmol/l glucose by 66 +/- 27% and 41 +/- 25%. Somatostatin secretion was inhibited to 72 +/- 2% (n = 5) of basal secretion by galanin at 10(-9) mol/l and to 65 +/- 7% (n = 7) at galanin at 10(-8) mol/l, both at 5 mmol/l glucose. At 8 mmol/l the figures were 83 +/- 6% and 70 +/- 10%. Insulin secretion in response to square wave increases in glucose concentration from 3.5 to 11 mmol/l (n = 5) increased 2-fold during simultaneous perfusion with galanin (10(-8) mol/l).     

The role of serum fructosamine as a screening test for gestational diabetes mellitus

The serum fructosamine concentration indicates the degree of glycation of serum proteins, particularly albumin, and reflects an average blood glucose level over the previous 1-3 weeks. Serum fructosamine, glycated haemoglobin (HbA1c), total serum protein, serum albumin, fasting plasma glucose and oral glucose tolerance test (OGTT) have been measured in 127 healthy control subjects, 102 type 1 and 152 type 2 diabetes mellitus patients and 106 nondiabetic pregnant women. Fructosamine concentration of 2.24 +/- 0.16 and 3.21 +/- 0.41 mmol/l (mean +/- S.D.) has been found in control subjects and diabetics respectively (P less than 0.001). During the second trimester a significantly lower fructosamine level (1.92 +/- 0.21 mmol/l) has been found in pregnant women, most likely due to the low serum albumin concentration (31.35 +/- 3.97 g/l). None of them had a fructosamine level above the normal limit of 2.55 mmol/l. On the other hand, 12 pregnant women showed a disturbed OGTT with normal fructosamine. If the serum fructosamine concentration was adjusted for 40 g/l albumin, then a mean fructosamine of 2.16 +/- 0.24 mmol/l was found in patients with gestational diabetes. Our results show that serum fructosamine has a similar diagnostic value as HbA1c for non-pregnant adults, but neither can replace OGTT for the diagnosis of gestational diabetes.     

Glycogen loading alters muscle glycogen resynthesis after exercise.

This study compared muscle glycogen recovery after depletion of approximately 50 mmol/l (DeltaGly) from normal (Nor) resting levels (63.2 +/- 2.8 mmol/l) with recovery after depletion of approximately 50 mmol/l from a glycogen-loaded (GL) state (99.3 +/- 4.0 mmol/l) in 12 healthy, untrained subjects (5 men, 7 women). To glycogen load, a 7-day carbohydrate-loading protocol increased muscle glycogen 1.6 +/- 0.2-fold (P < or = 0.01). GL subjects then performed plantar flexion (single-leg toe raises) at 50 +/- 3% of maximum voluntary contraction (MVC) to yield DeltaGly = 48.0 +/- 1.3 mmol/l. The Nor trial, performed on a separate occasion, yielded DeltaGly = 47.5 +/- 4.5 mmol/l. Interleaved natural abundance (13)C-(31)P-NMR spectra were acquired and quantified before exercise and during 5 h of recovery immediately after exercise. During the initial 15 min after exercise, glycogen recovery in the GL trial was rapid (32.9 +/- 8.9 mmol. l(-1). h(-1)) compared with the Nor trial (15.9 +/- 6.9 mmol. l(-1). h(-1)). During the next 45 min, GL glycogen synthesis was not as rapid as in the Nor trial (0.9 +/- 2.5 mmol. l(-1). h(-1) for GL; 14.7 +/- 3.0 mmol. l(-1). h(-1) for Nor; P < or = 0.005) despite similar glucose 6-phosphate levels. During extended recovery (60-300 min), reduced GL recovery rates continued (1.3 +/- 0.5 mmol. l(-1). h(-1) for GL; 3.9 +/- 0.3 mmol. l(-1). h(-1) for Nor; P < or = 0.001). We conclude that glycogen recovery from heavy exercise is controlled primarily by the remaining postexercise glycogen concentration, with only a transient synthesis period when glycogen levels are not severely reduced.     

Heterogeneity of sickle-cell anemia based on a profile of hematological variables.

Factors that influence the heterogeneity of the disease expression of sickle-cell anemia are not well understood. This study examines the ability of a profile of six hematological variables (HB, HCT, RBC, %Hb F, MCV, and %HBA2) to predict the severity of disease measured on 225 patients ranging from 0.2 to 18 years of age. Four subgroups of patients were identified separately in each sex using cluster analysis techniques. In each sex, mean hemoglobin concentration and percent Hb F increased across the four clusters from 7 to 10 gm/dl and from 7% to 16%, respectively. Mean cell volumes were approximately 90, 80, 90, and 75 in groups 1, 2, 3, and 4, respectively; thus MCV did not increase in an orderly progression along with HB and %Hb F. We studied the distribution of four anthropometric, five physical examination, and seven clinical measures of disease severity among clusters. In each sex, subgroups differed significantly (P less than .05) for percent ever hospitalized for sickle-cell anemia, percent ever transfused, and percent with bone-age delays greater than 1 year. In addition, male clusters differed significantly for percent ever having had pneumonia, priapism, or dactylitis, and females differed significantly for height and weight. %Hb F and its inverse relationship with %HBA2 was more highly associated with the measures of severity than the degree of anemia or MCV. This study establishes the utility of a vector of hematological variables as a predictor of heterogeneity of measures of clinical manifestations among young patients with sickle-cell anemia. The role of alpha-thalassemia and genetic factors that affect Hb F levels were considered as possible explanations for the observed heterogeneity.     

Selenium, glutathione peroxidases, and some other antioxidant parameters in blood of patients with chronic renal failure

In the present study several parameters associated with oxidative stress were examined in the blood of 25 chronic renal failure (CRF) patients and the results were compared with 18 healthy subjects. Mean creatinine concentration in patients was 1,216 +/- 292 micromol/l. Selenium (Se) concentration in red cells, whole blood and in plasma of CRF patients (106 +/- 32.5, 59.0 +/- 16.7 and 42.4 +/- 13.8 ng/ml, respectively) was significantly (0.0001 < P 0.01) lower (by 20-42%) compared with the controls. Red cell and plasma glutathione peroxidase (GSH-Px) activities (16.6 +/- 3.4 U/g Hb and 93.7 +/- 32.9 U/l plasma) were lower by 12 and 53% (P < 0.05 and < 0.0001, respectively) in patients than in healthy subjects. GSH concentration in red cells of patients (2.81 +/- 0.45 mmol/l) was significantly (P < 0.001) higher (by 20%) than in control group. Malonyldialdehyde (MDA) concentration (expressed as thiobarbituric acid-reactive substances) in red cells of patients (725 +/- 155 nmol/g Hb) was significantly (P < 0.001) higher (by 28%) than in control group. No significant difference was observed in the activity of superoxide dismutase in pLasma between the two groups. In conclusion, our results confirm that the aLterations in Se levels in blood components and in GSH-Px activity in plasma show that the kidney plays an important role in Se homeostasis and in plasma GSH-Px synthesis.     

Application of 31P MRS to the analysis of phospholipid changes in plasma of patients with acute leukemia

The aim of the experiment was to evaluate the changes of phospholipid concentrations in patients (n=30) with acute leukemia compared with reference group of healthy volunteers (n=21). The analysis focused on the following phospholipids (PL) collected from plasma: phosphatidylcholine (PC), plasmalogen of phosphatidylcholine (CPLAS), lysophosphatidylcholine (LPC), sphingomyelin (SM), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Phospholipid extracts were obtained by Folch's method from 4 ml of plasma. 31P MR spectra were obtained on an AMX Bruker 300 MHz (7.05 T) spectrometer. Calculation of concentration based on integral intensity of the phospholipid relative to an internal concentration standard of MDPA. For healthy volunteers, the following values of phospholipid concentrations were obtained: (5.18+/-1.615) mmol/l for PC+CPLAS; (0.364+/-0.178) mmol/l for LPC; (1.211+/-0.411) mmol/l for SM; (0.343+/-0.124) mmol/l for PI+PE. PLs of patients were assayed at least twice: at the time of diagnosis and, when appropriate, at the time of complete remission from the disease (CR). At the time of diagnosis, the mean concentrations of studied compounds were: (1.602+/-0.716) mmol/l for PC+CPLAS; (0.041+/-0.048) mmol/l for LPC; (0.398+/-0.198) mmol/l for SM; (0.045+/-0.071) mmol/l for PI+PE. After attainment of complete remission (CR), the respective values were as follows: (4.094+/-1.886) mmol/l for PC+CPLAS; (0.295+/-0.139) mmol/l for LPC; (1.123+/-0.634) mmol/l for SM; (0.230+/-0.125) mmol/l for PI+PE. All concentrations found in patients at the time of diagnosis were significantly lower than in reference group and in those benefited from complete remission (CR). By contrast the differences in concentrations of phospholipids in plasma between patients with complete remission (CR) and healthy volunteers were no statistically significant.     

Erythrocyte carbonic anhydrase I concentration in patients receiving thyroxine.

We recently reported that the red blood cell (RBC) carbonic anhydrase I (CAI) concentration in patients with hyperthyroidism is reduced and reflects the patient's mean thyroid hormone level over the preceding months. In this study, RBC CAI concentrations were measured in patients with thyroid nodules who were receiving suppressive doses of thyroxine (group I) and compared with those obtained in patients with primary hypothyroidism receiving replacement doses of thyroxine (group 2). Of the 17 patients in group 1, 16 (94%) had elevated plasma free T4 levels, but all 17 had normal free T3 levels. Of the 17 patients in group 2, 16 (94%) had normal free T4 levels and all 17 had normal free T3 levels. Plasma TSH concentrations in group 1 were all below the lower limit of sensitivity of 0.04 mU/l. In group 2, 11 had normal and 6 had slightly elevated plasma TSH concentrations. The mean (+/- SD) RBC CAI concentration in group 1 (300 +/- 53 nmol/g Hb) was significantly lower than that in group 2 (340 +/- 57 nmol/g Hb). The RBC CAI concentration was significantly correlated with both the concentration of plasma free T4 and free T3. These observations indicate that in patients receiving suppressive doses of thyroxine a slight increase in the plasma free T4 concentration produces a slight but significant decrease in RBC CAI levels.     

Changes in plasma high-density lipoprotein cholesterol concentration after weight reduction in grossly obese subjects.

Changes in serum lipoproteins associated with weight loss were assessed in 13 grossly obese (relative weight 183%) patients who had participated in an outpatient semi-starvation diet consisting of liquid protein and carbohydrate. At the follow-up examination an average of six and a half months after the start of refeeding the mean weight loss was 16.1 +/- 4.5 kg or 15% of initial body weight. Significant increases in high-density lipoprotein (HDL) cholesterol of 0.16 +/- 0.05 mmol/l (6 +/- 2 mg/100 ml) and decreases in triglycerides (0.8 +/- 0.23 mmol/l; 73 +/- 20 mg/100 ml) and fasting blood sugar (0.6 +/- 0.22 mmol/l; 11 +/- 4 mg/100 ml) were observed. Changes in HDL cholesterol correlated significantly with changes in weight (r = 0.667) and percentage change in weight. The intercept of the regression equation relating HDL cholesterol to percentage change in weight was -7.3, indicating that a change in HDL cholesterol greater than zero required a weight loss of at least 7.3% of body weight. Thus, weight loss can significantly increase HDL cholesterol concentrations but a considerable amount of weight must be lost to produce a significant increase in HDL cholesterol concentration.     

Diagnosing familial hypercholesterolaemia in childhood by measuring serum cholesterol.

The serum cholesterol concentrations of 134 children aged 1-16 years who had at least one first-degree relative with presumed familial hypercholesterolaemia showed a bimodal distribution, and, using the maximum likelihood technique, two overlapping curves could be fitted. The mean value of the affected children (heterozygotes) was 8-9 mmol/l and that of the unaffected 4-9 mmol/l. The two curves intersected at 6-77 mmol/l, and at this point 5% of the unaffected children had values over 6-77 mmol/l and 3-5% of the heterozygotes had values under 6-77 mmol/l. If this cholesterol concentration is used as a cut-off point 4-25% of cases would be misdiagnosed.     

Control of hepatic nitrogen metabolism and glutathione release by cell volume regulatory mechanisms

1. Urea synthesis was studied in isolated perfused rat liver during cell volume regulatory ion fluxes following exposure of the liver to anisotonic perfusion media. Lowering of the osmolarity in influent perfusate from 305 mOsm/l to 225 mOsm/l (by decreasing influent [NaCl] by 40 mmol/l) led to an inhibition of urea synthesis from NH4Cl (0.5 mmol/l) by about 60% and a decrease of hepatic oxygen uptake by 0.43 +/- 0.03 mumol g-1 min-1 [from 3.09 +/- 0.13 mumol g-1 min-1 to 2.66 +/- 0.12 mumol g-1 min-1 (n = 9)]. The effects on urea synthesis and oxygen uptake were observed throughout hypotonic exposure (225 mOsm/l). They persisted although volume regulatory K+ efflux from the liver was complete within 8 min and were fully reversible upon reexposure to normotonic perfusion media (305 mOsm/l). A 42% inhibition of urea synthesis from NH4Cl (0.5 mmol/l) during hypotonicity was also observed when the perfusion medium was supplemented with glucose (5 mmol/l). Urea synthesis was inhibited by only 10-20% in livers from fed rats, and was even stimulated in those from starved rats when an amino acid mixture (twice the physiological concentration) plus NH4Cl (0.2 mmol/l) was infused. 2. The inhibition of urea synthesis from NH4Cl (0.5 mmol/l) during hypotonicity was accompanied by a threefold increase of citrulline tissue levels, a 50-70% decrease of the tissue contents of glutamate, aspartate, citrate and malate, whereas 2-oxoglutarate, ATP and ornithine tissue levels, and the [3H]inulin extracellular space remained almost unaltered. Further, hypotonic exposure stimulated hepatic glutathione (GSH) release with a time course roughly paralleling volume regulatory K+ efflux. NH4Cl stimulated lactate release from the liver during hypotonic but not during normotonic perfusion. In the absence of NH4Cl, hypotonicity did not significantly affect the lactate/pyruvate ratio in effluent perfusate. With NH4Cl (0.5 mmol/l) present, the lactate/pyruvate ratio increased from 4.3 to 8.2 in hypotonicity, whereas simultaneously the 3-hydroxybutyrate/acetoacetate ratio slightly, but significantly decreased. 3. Addition of lactate (2.1 mmol/l) and pyruvate (0.3 mmol/l) to influent perfusate did not affect urea synthesis in normotonic perfusions, but completely prevented the inhibition of urea synthesis from NH4Cl (0.5 mmol/l) induced by hypotonicity. Restoration of urea production in hypotonic perfusions by addition of lactate and pyruvate was largely abolished in the presence of 2-cyanocinnamate (0.5 mmol/l). Addition of 3-hydroxybutyrate (0.5 mmol/l), but not of acetoacetate (0.5 mmol/l) largely reversed the hypotonicity-induced inhibition of urea synthesis from NH4Cl.(ABSTRACT TRUNCATED AT 400 WORDS)     

Muscle glycogen resynthesis during recovery from cycle exercise: no effect of additional protein ingestion.

In the present study, we have investigated the effect of carbohydrate and protein hydrolysate ingestion on muscle glycogen resynthesis during 4 h of recovery from intense cycle exercise. Five volunteers were studied during recovery while they ingested, immediately after exercise, a 600-ml bolus and then every 15 min a 150-ml bolus containing 1) 1.67 g. kg body wt(-1). l(-1) of sucrose and 0.5 g. kg body wt(-1). l(-1) of a whey protein hydrolysate (CHO/protein), 2) 1.67 g. kg body wt(-1). l(-1) of sucrose (CHO), and 3) water. CHO/protein and CHO ingestion caused an increased arterial glucose concentration compared with water ingestion during 4 h of recovery. With CHO ingestion, glucose concentration was 1-1.5 mmol/l higher during the first hour of recovery compared with CHO/protein ingestion. Leg glucose uptake was initially 0.7 mmol/min with water ingestion and decreased gradually with no measurable glucose uptake observed at 3 h of recovery. Leg glucose uptake was rather constant at 0.9 mmol/min with CHO/protein and CHO ingestion, and insulin levels were stable at 70, 45, and 5 mU/l for CHO/protein, CHO, and water ingestion, respectively. Glycogen resynthesis rates were 52 +/- 7, 48 +/- 5, and 18 +/- 6 for the first 1.5 h of recovery and decreased to 30 +/- 6, 36 +/- 3, and 8 +/- 6 mmol. kg dry muscle(-1). h(-1) between 1.5 and 4 h for CHO/protein, CHO, and water ingestion, respectively. No differences could be observed between CHO/protein and CHO ingestion ingestion. It is concluded that coingestion of carbohydrate and protein, compared with ingestion of carbohydrate alone, did not increase leg glucose uptake or glycogen resynthesis rate further when carbohydrate was ingested in sufficient amounts every 15 min to induce an optimal rate of glycogen resynthesis.     

Mechanisms of hypophosphatemia in humans with heatstroke

Hypophosphatemia is common in heatstroke, but little is known about its mechanism. We investigated 10 consecutive patients with heatstroke (mean age 58 +/- 2 yr) whose mean rectal temperature at admission was 42.3 +/- 0.2 degrees C. Eight patients presented with hypophosphatemia [0.48 +/- 0.08 mmol/l, normal range (NR) 0.8-1.4 mmol/l], associated with increased fractional excretion of phosphate (19.8 +/- 6.4%, NR 6-20%) relative to plasma phosphate levels and reduced renal threshold for phosphate (0.55 +/- 0.08 mmol/l glomerular filtrate, NR 0.8-1.4 mmol/l). Plasma parathyroid hormone (75.0 +/- 5 pmol/l) and calcium (2.24 +/- 0.02 mmol/l) levels and fractional excretion of calcium were normal (1.66 +/- 0.27%). There was no evidence of uricosuria or aminoaciduria, and only one patient had glucosuria. Arterial carbon dioxide was decreased in eight patients (28 +/- 1.1 Torr); however, none had elevated blood pH (7.35 +/- 0.02). The results suggest that heatstroke-related hypophosphatemia is associated with abnormal phosphaturia independent of the parathyroid hormone level, and there is no evidence of tubular dysfunction.     

Changes in serum levels of glycoprotein hormone alpha subunits in patients with alphoma-type pituitary tumors during LHRH and TRH stimulation tests

A group of 21 patients with the alphoma-type pituitary tumors was studied. In 9 cases the tumor was associated with acromegaly. Alpha subunit concentration was determined in all the patients and in control subjects in the course of dynamic tests consisting in simultaneous intravenous administration of 200 micrograms TRH and 100 micrograms LH-RH. In basal conditions the concentration of alpha subunit in patients with the alphoma-type tumors ranged between 2.1 and 30 micrograms/l (mean 7.5 +/- 6.6 micrograms/l), and in controls the respective values ranged between 0.2 and 1.6 micrograms/l (mean 0.78 +/- 0.36 micrograms/l). In the course of the LH-RH + TRH test there was an increase in the alpha subunit level both in the patients with alphoma associated with acromegaly and in the remaining cases of alphoma. Statistical analysis of the results obtained for the whole group of patients revealed a significant linear correlation between the alpha unit concentration 20, 30, 60 and 90 minutes following stimulation with the neurohormones and that before stimulation. For 9 patients with the acromegaly-associated tumors a statistically significant increase in the alpha subunit concentration was noted only at the 90-th minute of the stimulation test, while for the remaining 12 patients with alphoma an increase was statistically significant for the whole time of the duration of the test. In healthy subjects the concentration of alpha subunit never exceeded the limits of the normal values in the course of the LH-RH + TRH stimulation test.