Erythrocyte Sodium Concentration Research Articles

Changes of the erythrocyte phenotype and blood biochemistry in dairy calves during the first ten weeks of age.

BackgroundBovine erythrocytes undergo important changes in their morphology and chemical composition during the first weeks of age, which must be understood to accurately interpret hematology results in calves. The objectives of this prospective cohort study were to describe physiological changes of calf erythrocytes and to investigate mechanisms potentially causing these changes.MethodsBlood samples from 30 clinically healthy dairy calves were obtained from birth to the tenth week of age in weekly intervals. Hematological and plasma biochemical parameters as well as the mineral electrolyte content of erythrocytes were determined and followed over time. The changes of parameters characterizing the erythrocyte phenotype over time were compared to the changes of plasma and erythrocyte biochemical parameters and possible associations were investigated using correlation and stepwise regression analyses.ResultsAlthough the erythrocyte mean corpuscular volume (MCV) declined from 43.6 ± 3.7 fL to 35.6 ± 3.2 fL between the first and seventh week, the red blood cell count (RBC) increased from 7.2 ± 1.1 × 1012/L to 9.3 ± 1.0 × 1012/L until the fifth week of age. The blood hemoglobin (Hb) concentration increased from 0.96 ± 0.16 g/L to 1.16 ± 0.11 g/L in the first three weeks of age and remained at this level until the end of the study. Changes in MCV were accompanied by a decline of the erythrocyte potassium content (KERY) from 91.9 ± 13.5 to 24.6 ± 7.2 mmol/L and a concomitant increase of the erythrocyte sodium content from 45.0 ± 32.0 to 102.7 ± 26.5 mmol/L. MCV was found to be associated with KERY, the primary determinant of the intra-erythrocyte osmotic pressure from the sixth week of age and with blood hemoglobin, the primary determinant of the intra-erythrocyte oncotic pressure from the eighth week of age, when KERY, blood Hb and MCV already had reached or approached normal levels of adult cattle. The plasma iron concentration was not found to be associated to any of the studied hematological parameters.ConclusionA volume reduction of 20% in bovine neonatal erythrocytes is a physiological change occurring during the first weeks of age and is neither associated with sideropenia nor with anemia in healthy calves. The mechanism driving the observed erythrocyte volume change could not be identified. Results of the correlation and regression analyses indicate that changes in intra-erythrocyte osmotic or oncotic pressure are improbable underlying causes. Results reported here show that KERY is an unreliable indicator for the K homeostasis of the intracellular space in neonatal calves and that a decrease in MCV in early life per-se is an unreliable indicator for the development of microcytic anemia.

ERYTHROCYTE CATIONS IN THE ADAPTATION PROCESS IN PERCH PERCA FLUVIATILIS L. (PERCIDAE)

The concentration of sodium and potassium ions in erythrocytes in perch Perca fluviatilis L. was compared to that in ten other freshwater fish species. The cation concentration was determined by flame photometry. The participation of erythrocyte cations in the buffer and respiratory processes that promote the specific resistance of perch to unfavorable factors is substantiated. Among the investigated fish species, the highest sodium concentrations in red blood cells were found in perch and pike, who are the most resistant to water acidification. High sodium concentration in red blood cells indicates a high alkalization capacity of the erythrocytes’ inner environment and is one of the mechanisms for enhanced resistance of perch to water acidification. In perch the potassium concentration in erythrocytes is at the lower limit of the range typical for fish resistant to hypoxia. A high potassium level in red blood cells is regarded as one of the mechanisms for promoting the tolerance of perch to hypoxia. Analysis of data from the literature revealed the same kind of participation of erythrocyte sodium in buffer processes and erythrocyte potassium in respiratory processes in marine fish as in freshwater fish. When determining the level of hematocrit, higher values of this parameter were found in perch as compared to other freshwater fish. Other known physiological and biochemical mechanisms for promoting total and specific resistance of perch to detrimental factors are also analyzed in the paper.

Erythrocyte potassium and glutathione polymorphism determination in Saanen x Malta crossbred goats

Hand K L associated with the potassium concentration were calculated as 0.94 and 0.06, respectively. The differences between the mean values of low and high potassium concentrations in erythrocyte were statistically significant (P < 0.01). In addition, there were some significant relationships between erythrocyte potassium types and some blood parameters such as whole blood sodium and potassium concentrations, erythrocyte sodium and potassium concentrations and total monovalent cation concentration in erythrocyte (P < 0.05). The allele gene frequencies of GSH H and GSH h related with the glutathione concentration were calculated as 0.43 and 0.57, respectively. The difference between the mean values of low and high glutathione erythrocyte concentrations were also statistically significant (P < 0.01). Finally, the significant correlation coefficient between erythrocyte sodium and potassium concentrations was observed in this study (P < 0.05).

Intracellular sodium and potassium concentrations in erythrocytes of healthy male subjects.

Intracellular sodium and potassium concentrations in erythrocytes of healthy male subjects.

Erythrocyte potassium, sodium and glutathione concentrations and their relationship with reproduction, body weight and fleece weight traits in Awassi sheep

Abstract. Relationship between erythrocyte potassium (Ke), erythrocyte sodium (Nae) and blood glutathione (GSH) concentrations and production/ reproduction traits were investigated in Awassi sheep. Thirty healthy sheep subjected to analyze for phenotypic and gene frequencies of Ke, Nae and GSH concentrations. Correlation between these parameters and production/ reproduction traits such as greasy fleece weight, milk production, birth rate, single and twin birth rate and body weight were calculated. A positive correlation was found between birth rate and mean Ke concentration (r=0.481, P&lt;0.008) and Nae concentration (r=−0.454, P&lt;0.013). Another correlation between GSH concentration and greasy fleece weight (r=−0.368, P&lt;0.049) and milk production (r=0.379, P&lt;0.050) parameters was also evidenced. These suggest that Ke, Nae and GSH concentrations may be included in the metabolic profile testing parameters.

Changes in the concentration of sodium and potasium in erythrocytes during pregnancy in patients with and without essential hypertension

To date, there is scant information on the relation between pregnancy and the intracellular Na+ and K+ content in patients with essential hypertension. The aim of this study is to determine the changes in the concentrations of Na+ and K+ in erythrocytes of patients diagnosed with essential hypertension in pregnancy. We studied a group of 204 Polish women in ambulatory conditions. During pregnancy all women had no dietary restrictions, did not take any medications, and were non-smokers. We divided the patients into 3 groups. From a cohort of 84 women (mean 29.5 ±5.5 years of age) diagnosed with essential hypertension before the pregnancy by complete clinical examination and appropriate laboratory investigation with definite exclusion of the secondary casuses of HTN, we assembled 2 groups of hypertensive women. In the first group diagnosed with HTN before pregnancy, BP did not exceed 140/90 mmHg throughout the time of pregnancy (HTN, BP<140/90 mmHg). The second group had BP between 140/90 and 160/110 mmHg during pregnancy (HTN, BP>140/90 mmHg). The third group of patients had normal BP, but had a family history of HTN in, at least, one of parents. The forth group of normotensive 60 women (mean 28.5 ±4.9 years of age) was used as a control group. We took a sample of blood from each patient for measurments of Na+ and K+ on 3 occasions throughout the pregnancy: between weeks 8 and 12, 24 and 28, 34 and 38 of gestation and additionally 4 months after the delivery. The lowest values of the concentration of intracellular Na+ in all groups occured between weeks 34–38 in the group of normotensive patients with FH+ (10,93 +/-0,64mmol/l) (p<0,05).The only significant difference in the concentration of intracelullar K+ occured between the weeks 8 and 12 of pregnancy when values of the concentration of K+ in the erythrocytes were significantly lower in the groups of HTN>140/90 mmHg compared to all other groups (p<0,01). This disparity disapeared later in the pregnancy.We have recorded a statistically significant elevation in the concentration of intracellular K+ inside the group of HTN>140/90 mmHg during the pregnancy (p<0,05).

Leptin association with erythrocyte sodium content in obesity-related hypertension

Insulin resistance is frequently associated with obesity-related hypertension. Leptin resistance and increased plasma leptin levels are frequent companions in this association. To examine whether in obesity hypertension with insulin resistance, plus hyperleptinemia, the sodium content of erythrocyte (Naie) reflects a positive sodium balance related to the physiological loss of leptin in sodium reabsorption, we studied a group of obese hypertensive patients, and a group of lean normotensive subjects. In obese hypertensives, fasting glucose, insulin and the insulin resistance index were higher as compared to the lean individuals (107.0 ± 4.1 mg/dl, 10.2 ± 1.4 pU/ml and 2.94 ± 0.52, respectively, vs 98.7 ± 4.1 mg/dl, 7.22 ± 1.33 U/ml, and 1.79 ± 0.16, respectively, p < 0.002). Both the leptin/BMI 2 index as well as the Naie were significantly higher in the obese hypertensive group as compared to control group (1.9± 0.21 vs 1.25 ± 0.27, respectively p < 0.01, and 12.5 ± 0.51 vs 10.7 ± 0.5 mEq/ml/cell, respectively p < 0.05). In obese hypertensives the leptin/BMI 2 index was significantly associated with DBP (r= = 0.41, p < 0.04), MBP (r= 0.44, p < 0.03), Naie (r = 0.41, p < 0.05) and age (r = 0.43, p = 0.03). We conclude that in obese hypertensive patients Naie is increased reflecting a state of positive sodium balance. In these patients, the elevated circulating leptin concentrations were one of the main regulators of the content of sodium in erythrocytes.

Alteration in ouabain-sensitive sodium potassium pump of erythrocytes during pregnancy induced hypertension: a kinetic study.

The erythrocytes are widely used as model cells for studies of sodium-potassium pump (Na(+)-K(+) pump) in health and disease. Hence, to explore the possible role of the Na(+) transport across the cell membrane in the pathogenesis of pregnancy-induced hypertension (PIH), the present study was conducted to assess the Na(+)-K(+) pump functions in relation to its intrinsic kinetic properties using erythrocytes (RBC). Erythrocyte sodium concentration in pregnancy-induced hypertensive women was significantly (p<0.01) lower in comparison to normotensive pregnant women. On the contrary erythrocyte potassium was significantly higher (p<0.01) in PIH women as compared to normotensive pregnant women. Observed alterations in Na(+) and K(+) concentrations in erythrocytes were associated with significantly (p<001) increased Ouabain-sensitive sodium efflux rate and rate constants in erythrocytes from PIH women. Further, kinetic studies revealed that increased Ouabain-sensitive efflux rate constant in RBC from PIH women was accompanied by increased maximal velocity (V(max)) of Na(+)-K(+) pump. However, the affinity constant (K(m)) was unaltered in both the groups. Therefore, these findings suggest that increased Na(+)-K(+) pump activity in RBC of PIH women could be due to either increased numbers of Na(+)-K(+) pump units of increased numbers of active subunits of Na(+)-K(+) pump possibly due to specific plasma factors in PIH women.

Low-renin hypertension, altered sodium homeostasis, and an alpha-adducin polymorphism.

Defining the genetic basis of common forms of human essential hypertension is most informative when correlated with physiological mechanisms that underlie blood pressure regulation. A polymorphism of the alpha-adducin gene as been associated with elevated blood pressure in the rat, but previous studies of the 460Trp polymorphism of the human alpha-adducin gene have not clearly identified an association with hypertension. In this study, the frequency of the 460Trp allele was 19% and 9 of 279 subjects (3.2%) were homozygous for the 460Trp allele. The systolic blood pressure response to changes in dietary sodium was significantly greater in subjects homozygous for the 460Trp allele (25 +/- 4 mm Hg) compared with subjects heterozygous for 460Trp (12 +/- 2 mm Hg) or homozygous for the 460Gly allele (14 +/- 1 mm Hg). Intracellular erythrocyte sodium content, sodium-lithium countertransport, and renal fractional excretion of sodium were significantly decreased in subjects homozygous for the 460Trp polymorphism (P<0.05). There was a significant association between homozygosity for the 460Trp allele and low-renin hypertension. Subjects heterozygous for the 460Trp allele did not have increased salt-sensitivity or an increased frequency of low-renin hypertension. Therefore, this study demonstrates a common genetic basis for altered cellular sodium homeostasis, impaired renal sodium handling, and salt-sensitivity of systolic blood pressure in individuals homozygous for the 460Trp polymorphism of the alpha-adducin gene. Homozygosity for this alpha-adducin allele may be an important determinant for approximately 10% of individuals with low-renin hypertension.

Homozygosity for an Alpha-Adducin Polymorphism (460TRP) Is Associated with Salt-Sensitivity and Low-Renin Hypertension in Humans

P133 Single nucleotide polymorphisms of the adducin genes have been associated with the development of elevated blood pressure in the rat. However, previous studies of the 460Trp polymorphism of human alpha-adducin have not clearly identified an association with the development of human hypertension. In this study, 281 hypertensive subjects were subgrouped by the intermediate phenotypes of plasma renin status and sensitivity of systolic blood pressure to dietary sodium. The frequency of the 460Trp allele was 19% and 9 of 281 subjects (3.2%) were homozygous (TT) for the 460Trp allele. The systolic blood pressure response to changes in dietary sodium (&gt;150 meq/d vs. ≤30 meq/d) was significantly (p &lt; 0.05) greater in TT subjects (25 ± 2 mmHg) compared to those heterozygous (GT) for the 460Trp allele (12 ± 2 mmHg) or homozygous (GG) for the 460Gly allele (14 ± 1 mmHg). There was a significant (p &lt; 0.005) association between homozygosity for the 460Trp allele and low-renin hypertension. Six of 67 (9%) low-renin subjects, but only 3 of 214 (1.4%) normal- renin subjects had the TT genotype. Heterozygous (GT) subjects did not have increased salt-sensitivity of systolic blood pressure and did not have an increased frequency of low-renin hypertension. Erythrocyte sodium content was significantly (p &lt; 0.01) less in subjects with the TT genotype (24.5 ± 1.0 mmol/kgHgb) compared to all subjects (33.2 ± 0.4 mmol/kgHgb). Subjects with the TT genotype had a significantly (p &lt; 0.05) lower sodium-lithium countertransport (SLC) (0.16 ± 0.04 mmol/l/h) than other subjects (0.28 ± 0.01 mmol/l/h). However, the mean SLC of all low-renin hypertensive subjects (0.25 ± 0.02 mmol/l/h) was not significantly different than the mean SLC of normal-renin hypertensive subjects (0.26 ± 0.01 mmol/l/h). Thus, a decreased SLC is associated with the TT genotype and is not a characteristic of all individuals with low-renin hypertension. These findings suggest that homozygous expression of the 460Trp polymorphism of the alpha-adducin gene alters sodium handling in humans and may be an important contributor to the development of low-renin hypertension in some individuals.

Effects of ethoxyquin on the blood composition of turbot, Scophthalmus maximus L.

Ethoxyquin (6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline (EQ) is a synthetic antioxidant used for preventing rancidity in animal foodstuffs. Three groups of ten fish were given a diet containing respectively 75 (control group with the commercial food), 200 and 400 ppm EQ for 16 days. The control group had a plasma osmolality and chloride concentration within the normal range of marine teleosts, but sodium concentrations of only about 110 mM, indicating the presence in the plasma of substantial amounts of another cation. Fish given food with 400 ppm EQ displayed a 70 mM increase in the plasma concentration of sodium. This indicates that EQ has disturbed the iono-regulatory mechanisms, probably by reducing the ATP production or inhibiting directly the Na/K-ATPase in the gills. The large increase in plasma sodium concentration was not accompanied by any significant increase in plasma osmolality, indicating that at least a part of the sodium added to the plasma is made osmotically inactive. In spite of the elevated plasma sodium concentration, the sodium content of erythrocytes of the 400-ppm EQ fish was reduced to half, while the content of calcium was unaffected. The transmembrane energy gradient of sodium in the EQ exposed turbot obviously increased, allowing them to use a sodium coupled antiport system to keep the cellular calcium content low when the Ca-ATPases is blocked. A mechanism of this kind is also likely to be important to turbot that experience hypoxia under natural conditions. The 400-ppm group also displayed a substantial increase in liver weight, but the physiological significance of this effect is not clear. The leucocyte counts indicated the absence of obvious immunological effects.

Relationship Between Salt And Blood Pressure In Hypertensive Patients On Chronic ACE-Inhibition

We investigated the effect of a 4-day oral salt load (150 mmol NaCl extra per day) on blood pressure, erythrocyte sodium transport and the activity in the renin-angiotensin system in six males with primary hypertension, who had attained normotension on chronic enalapril treatment for 4 years. The design was a placebo-controlled, randomized, two-way cross over, double-blind study, i.e. each patient served as his own control. Intracellular erythrocyte sodium and potassium content were measured by flame photomometry. The increase in the intracellular sodium concentration during 1 h in 37 degrees C incubation of whole-blood with ouabain (compared with no-ouabain) was measured to determine the rate of active sodium efflux. 24-h blood pressure registration was performed with Space-lab equipment (SL 90202) before and at the end of the salt load. Left ventricular morphology was evaluated with echocardiography and the minimal vascular resistance of the hand vascular bed with water plethysmography at baseline and after 4 years on enalapril. Four years' enalapril treatment caused a significant decrease in blood pressure, left ventricular mass and minimal vascular resistance. During the 4-day salt load average 24-h blood pressure was significantly elevated, 129+/-3/85+/-2 mmHg as compared to 124+/-2/82+/-2 mmHg during placebo treatment (p=0.025). The change (delta) in MAP during high salt intake showed a negative relationship to delta-sodium efflux rate constant (r=-0.65, p=0.047). No significant relationship was found between the blood pressure response to the salt load and structural cardiovascular changes. In conclusion, a short-term oral salt load in hypertensive patients on chronic enalapril treatment caused a blood pressure rise, which was related to cellular sodium transport but not to structural cardiovascular changes.

Mechanisms of echinocytosis induced by Crotalus atrox venom.

Transient echinocytosis has been reported in association with snake envenomation in humans and dogs. An in vitro model of echinocytosis induced by venom of crotalus atrox (western diamondback rattlesnake) was established to characterize erythrocyte morphologic changes and to investigate potential mechanisms of echinocytic transformation. Erythrocyte morphologic changes produced after the addition of venom to canine, feline, equine, and human blood were characterized by dose-dependent echinocytosis. Type III echinocytosis were consistently induced in vitro at a dose comparable to in vivo envenomation; higher venom doses produced spheroechinocytic and spherocytic transformations. The changes could not be induced in vitro in the presence of ethylenediaminetraacetic acid but were observed in heparinized and citrated blood samples, suggesting the participation of calcium or a metalloprotein in echinocytic change. These findings suggest that phospholipase A2 (PLA2), a calcium-dependent enzyme in snake venom, may be responsible for echinocytic transformation via the production of lysolecithin, a known echinocytic agent. Purified PLA2 from C. atrox venom induced dose-dependent echinocytic change in vitro in canine blood. Other potential mechanisms of echinocytic change evaluated in canine blood included erythrocyte cation loss and erythrocyte ATP depletion. In canine blood mixed with venom, erythrocyte sodium and potassium concentrations were consistently less than those of controls, likely as a result of membrane alteration produced by the actions of PLA2. There was no difference in blood ATP concentrations from dogs with snakebite when compared with normal controls; however, the power of this comparison was low. Echinocytosis induced by rattlesnake venom is related to the degree of venom exposure and may correlate clinically with the amount of venom absorbed. Echinocytic transformation in vitro is induced by PLA2 present in venom.

Role of the renal kallikrein–kinin system in the development of hypertension

Role of renal kallikrein–kinin system has been studied using mutant Brown-Norway Katholiek (BN-Ka) rats, in which both high- and low- molecular weight kininogens were almost absent in plasma and kinin in urine was mainly not detectable. Mutant BN-Ka rats were very sensitive to increased salt intake, resulting in raised systemic blood pressure that is linked to reduced urinary excretion of sodium, when compared with normal BN-Kitasato (BN-Ki) rats. Consequently, sodium accumulated in erythrocytes and cerebrospinal fluid in mutant BN-Ka rats. Subcutaneous infusion of angiotensin II (20 mg/day/rat) also enhanced the concentration of sodium in erythrocytes and in cerebrospinal fluid and increased the systemic pressure by releasing aldosterone. A 4-day infusion of 0.3 M sodium solution (6 ml/kg/h) to the abdominal aorta of conscious and un-restrained mutant BN-Ka rats increased the pressor responses of the arterioles to norepinephrine and angiotensin II (i.a.) by 30- and 10-fold, respectively. Infusion of ebelactone B, (a selective inhibitor of carboxypeptidase Y-like exopeptidase, a kininase in rat urine), to normal BN-Ki rats during induction of hypertension with DOCA and salt, resulted in the reduction of the raised blood pressure, indicating that a site of action of kinins was at the luminal membrane of the renal tubule cells. Our results support the view that the role of renal kallikrein–kinin system is to excrete `excess sodium' and a reduction in the generation of renal kinins may be a factor in the development of hypertension as a result of the sodium accumulation in the body.

Physiological characteristics and hormonal profile of young normotensive men with exaggerated blood pressure response to exercise.

Exaggerated blood pressure (BP) response to exercise in normotensive subjects is considered as a predictor of future hypertension. The aim of the study was to find out whether elevated BP response to exercise is associated with any other haemodynamic, metabolic or hormonal abnormalities. Abnormal BP response to exercise, i.e. systolic BP (SBP) > 200 mmHg at 150 W or lower workload, was found in 37 out of 180 normotensive, male students, aged 20-24 years. Fifteen students with elevated exercise BP (group E) volunteered for further examinations. Their resting and ambulatory BP showed high normal values. Eight of them had a family history of hypertension. Four subjects met the criteria of cardiac hypertrophy. Significant correlations were found between exercise SBP and left ventricular mass index, average 24 h and daytime SBP recordings. In comparison with normal subjects of the same age (group N, n = 13), those from group E did not differ in body mass index, plasma lipid profile, fasting glucose, insulin and catecholamine (CA) concentrations, but had increased erythrocyte sodium content, slightly elevated plasma renin activity and cortisol level. During exercise, E subjects showed greater cardiac output (CO) increases with normal heart rate, total peripheral resistance (TPR) and plasma CA. There were no significant differences between groups in haemodynamic and plasma CA responses to posture change from supine to standing. Glucose ingestion (75 g) caused smaller increases in CO and smaller decreases in TPR in E than in N subjects without differences in BP, blood glucose plasma insulin and CA. It is concluded that young normotensive men with exaggerated BP response to exercise show some other characteristics that may be considered as markers of predisposition to hypertension or factors promoting the development of hypertension.

Low erythrocyte Na/K-pump activity and number in Northeast Thailand adults: Evidence suggesting an acquired disorder

Healthy northeastern Thais have a higher erythrocyte sodium concentration and a lower erythrocyte membrane Na,K-adenosine triphosphatase (ATPase) activity than central Thais. To elucidate whether the defect is hereditary or acquired, we studied plasma sodium and potassium and erythrocyte sodium, potassium, Na,K-ATPase activity, and ouabain-binding sites (OBS) in the following groups: healthy newborns of ethnic central Thais (group 1), healthy newborns of ethnic northeast Thais (group 2), healthy adults of central Thailand ethnicity who lived in the rural central region (group 3) or in Bangkok (group 4), healthy adults of northeast Thailand ethnicity who lived in the rural northeast region (group 5) or who migrated to work in Bangkok for at least 1 year (group 6). Erythrocyte Na was higher in group 2 than in group 1. Group 3 had lower erythrocyte Na,K-ATPase activity than group 4, and it was lower in group 5 than in group 6. Among all groups, group 5 had the highest erythrocyte Na (11.6 mmol/L, F < 0.0001) and the lowest Na,K-ATPase activity (63 mmol Pi/mg · h, F < 0.0001) and erythrocyte OBS (397 sites per cell, F < 0.05) than the other adult groups. There was a positive correlation between erythrocyte Na,K-ATPase and erythrocyte OBS ( r = .416, P < .0001). Multiple regression analysis demonstrated a correlation between erythrocyte Na as a dependent variable and erythrocyte OBS, plasma potassium, erythrocyte potassium, and erythrocyte Na,K-ATPase ( r = .517, P < .0001). The erythrocyte Na,K-ATPase/OBS ratio, an expression of Na,K-ATPase activity equalized for the number of Na,K-pump units, was lowest among rural adults of the central region (group 3) and the northeast region (group 5) (F < 0.0002). Our data suggest that rural dwellers in Thailand tend to have lower erythrocyte Na,K-ATPase activity than urban dwellers and that this is probably acquired after birth. It was more severe among those from the northeast versus the central region, and was less severe among those who migrated to an urban area. This defect in northeast rural dwellers was probably associated with low numbers of Na,K-pump units and a defect of the pump to express activity, whereas in central rural dwellers it was probably associated with the latter condition. We postulate that there might be circulating Na,K-pump inhibitors and metabolic disturbances that cause attenuation of Na,K-ATPase function and synthesis in the northeast Thailand rural population, and that such substances may have an environmental origin. There may be a relationship between these abnormalities and sudden unexpected deaths.

Effects of gramicidin and tryptophan-N-formylated gramicidin on the sodium and potassium content of human erythrocytes

In order to get a better understanding in the mechanism by which tryptophan-N-formylated gramicidin (NFG) and gramicidin kill the malaria parasite Plasmodium falciparum in vitro, we studied the capacity of these peptides to change the potassium, as well as the sodium, composition of normal human erythrocytes, and their ability to cause cell lysis. It is shown that both peptides are able to induce potassium leakage from, and sodium flux into, erythrocytes in such a manner that it is most likely that they are able to form cation channels in the membrane of these cells. For both peptides, potassium efflux proceeds at a faster rate than sodium influx, but this difference is greater for NFG than for gramicidin. This explains the observation that gramicidin is more lytic than NFG is, even when comparing concentrations that show the same antimalarial activity. The finding that gramicidin is approximately 10 times more active than NFG in causing potassium efflux from normal erythrocytes, as well as in killing the malaria parasite, supports the hypothesis that peptide-induced parasite death is related to their capacity to induce potassium leakage from infected erythrocytes. Finally, the observation that erythrocytes are able to restore their normal ion contents after losing more than 50% of their potassium content by incubation with NFG or gramicidin, suggests that, in vivo, and upon treatment with drug concentrations that cause full inhibition of parasite growth, these cells would not be irreversibly damaged by action of the drugs.

Magnesium metabolism in hyperthyroidism.

Changes in magnesium metabolism, along with those in sodium, were investigated in 17 patients with Graves' disease (14 females and 3 males, mean +/- SD, 44.8 +/- 12.2 years) and their relationship to plasma levels of thyroid hormones were assessed before and after treatment. Each patient was studied in hyperthyroid state and euthyroid state after treatment. Each patient was studied in hyperthyroid state and euthyroid state after treatment with methimazole. Treatment with methimazole increased the magnesium concentration both in erythrocytes (2.00 +/- 0.18 vs. 2.08 +/- 0.24 mmol/l cells, P < 0.05) and in serum (0.72 +/- 0.12 vs. 0.84 +/- 0.11 mmol/l, P < 0.001) but both urinary output and fractional excretion of magnesium decreased significantly (P < 0.05 and P < 0.001, respectively). The erythrocyte sodium concentration decreased with treatment (10.7 +/- 2.6 vs. 8.1 +/- 1.1 mmol/l cells, P < 0.001) but the serum sodium remained unchanged (140.9 +/- 1.9 vs. 140.9 +/- 2.1 mmol/l, NS). Urinary excretion of sodium also decreased with treatment (P < 0.05), but only changes in indices of magnesium metabolism (decrease in renal fractional excretion, rise in serum level) correlated significantly with those of the thyroid functions with treatment. These observations clearly indicate that in Graves' disease, the magnitude of magnesium metabolism alteration is closely related to the extent of the increase in thyroid hormones in plasma.

Intracellular (polymorphonuclear) magnesium content in patients with bronchial asthma between attacks.

Previous studies have demonstrated the role of polymorphonuclears in asthma, the importance of increases in intracellular concentrations of ionized calcium in the release of chemical mediators, the role of magnesium as natural calcium channel blocker, and the importance of magnesium deficiency in plasma histamine concentration and in tissue prostanoid concentration. The objective of our study was to measure the polymorphonuclear magnesium content in patients with asthma in the interval between attacks. We measured the polymorphonuclear magnesium content, and serum and erythrocyte sodium, calcium, and magnesium concentrations in 21 healthy volunteers and 50 patients with different types of asthma. In our patients, the polymorphonuclear magnesium content was lower than in the control group (P < 0.001), while magnesium levels in erythrocytes and serum and the levels of other ions in erythrocytes and serum were normal. This is the first report to document low polymorphonuclear magnesium content in patients with bronchial asthma. The reduction of polymorphonuclear magnesium content may have an important role in the pathogenesis of asthma.

Predictors of blood pressure and left ventricular mass in the young: the Hypertension in Pregnancy Offspring Study.

The present study evaluates potential predictors for the future blood pressure and left ventricular mass in children. Fifty-two children were studied at mean age 12.6 +/- 1.5 years and reexamined after 5.6 years. Thirty-six children were born to mothers who had hypertension during pregnancy and 16 children were born after normotensive pregnancies by mothers who remained normotensive at follow-up. Blood pressure was measured at rest and during physical exercise. Left ventricular mass was calculated from M-mode echocardiography, and erythrocyte sodium and potassium concentrations were determined. A stepwise multiple linear regression analysis was used to predict subsequent blood pressure and left ventricular mass. Final systolic blood pressure was best explained by initial systolic blood pressure, erythrocyte potassium concentration, gender, and erythrocyte sodium concentration. Final diastolic blood pressure was best explained by erythrocyte potassium concentration. Gender and initial left ventricular mass were predictors of left ventricular mass at follow-up. This prospective study corroborates previous findings that blood pressure measured in children predicts their future blood pressure. Furthermore, an independent inverse relationship between childhood erythrocyte potassium concentration and adolescent blood pressure is demonstrated. Male gender and an early increased left ventricular mass are independent predictors of an increased left ventricular mass in adolescents.