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Biomedical subjects

L L Ng

Publications and source records attributed to L L Ng.

At least 109 records · Page 6Linked to original sources
PubMed1990

Evidence for abnormal Na+/H+ antiport activity detected by phosphorus nuclear magnetic resonance spectroscopy in exercising skeletal muscle of patients with essential hypertension.

1. Exercise-induced pH changes in skeletal muscle were studied in a group of eight subjects with essential hypertension by using 31P n.m.r. spectroscopy. 2. Leucocyte Na+/H+ antiport activity was measured in vitro in the same subjects using a pH-sensitive fluorescent dye. 3. Resting skeletal muscle pH and unstimulated leucocyte pH values were similar to those in control subjects, but increased Na+/H+ antiport activity was demonstrated in the leucocytes from hypertensive subjects by acid loading in vitro. Decreased skeletal muscle acidification and an increased rate of pH recovery was also demonstrated in vivo in these same patients during an acid load induced by isotonic exercise. 4. These findings suggest that the increased cellular Na+/H+ antiport activity, which has been demonstrated in vitro in essential hypertension, also affects the biochemical response of skeletal muscle to physiological levels of exercise. This strengthens the argument that increased Na+/H+ antiport activity in hypertension is a generalized and physiologically relevant cellular abnormality.

Biological Transport, Active↗
PubMed1990

Kinetics of the human leucocyte Na(+)-H+ antiport in essential hypertension.

Many membrane abnormalities have been described in human essential hypertension that may lead to an increased intracellular Na+ content, an example being reduced Na+ efflux by the sodium pump. We have previously found increased Na(+)-H+ antiport activity in leucocytes of hypertensive subjects. In the present study we examined the kinetics of this pump in 16 hypertensive and 20 carefully matched normotensive subjects by loading cells to different intracellular pH levels (as measured by fluorimetry) using a double-ionophore technique. The maximal rate of ethyl isopropyl amiloride-sensitive H+ efflux was significantly raised in leucocytes from the hypertensive subjects [75.3 +/- 6.2 versus 48.8 +/- 2.1 mmol/l per min in normotensives (mean +/- s.e.m.); P less than 0.001]. There was no difference in the affinity of the Na(+)-H+ antiport for intracellular H+. Intracellular buffering power at different internal pH levels in the range 6.0-7.1 did not differ in the two groups. We conclude that one reason for the reported intracellular alkalinity and increased sodium content of leucocytes from hypertensive subjects in bicarbonate-free media could be an increased number of active Na(+)-H+ exchangers or an increased turnover rate for each exchanger. A similar defect in vascular smooth muscle could account for the increased tone and thickening of the media. The abnormal maximal transport capacity of the leucocyte may be a useful membrane marker for future studies in human hypertension.

Biological Transport, Active↗
PubMed1990

Cellular sodium influx is low in type 1 (insulin dependent) diabetes.

Leucocyte sodium influx was studied in 29 type 1 (insulin dependent) diabetic subjects and compared to 24 non diabetic controls matched for age, body mass index and blood pressure. Total sodium influx from a low external concentration ((Na+) = 10 mmol/l) was reduced in type 1 diabetes (0.23 vs 0.31 mmol/l/min, p less than 0.05) as was amiloride insensitive sodium influx (0.09 vs 0.13 mmol/l/min, p less than 0.01). No difference was found in amiloride sensitive flux. No ionic flux was correlated with plasma glucose or insulin concentrations or with HbA1 levels. Intracellular sodium accumulation in type 1 diabetes is not due to an increase in total sodium influx, as judged from an external concentration of 10 mmol/l.

Adult↗
PubMed1990

Application of minimal models to measuring insulin sensitivity.

Bergman's minimal model of glucose dynamics was used to analyse intravenous glucose tolerance tests in non-diabetic and non-insulin dependent diabetic subjects (NIDDM). This analytical approach yielded an index of insulin sensitivity in 63% of the non-diabetic and 15% of NIDDM subjects. When the model was constrained to search for the most likely parameter solutions, all the non-diabetic and 96% of the diabetic plasma insulin-glucose curves could be solved. A comparison of the insulin sensitivity index derived from this constrained minimal model against the metabolic clearance rate of glucose during a hyperinsulinaemic clamp carried out on the same subjects showed a correlation of 0.84 (P less than 0.01, N = 12 normal subjects) and 0.65 (P less than 0.001, N = 21 NIDDM patients). We conclude that this modification of the minimal model may improve the number of intravenous glucose tolerance tests capable of systematic analysis in NIDDM subjects, giving a measure of insulin sensitivity that correlates with more established measures of this parameter.

Blood Glucose↗
PubMed1989

Altered stoichiometry of the human leucocyte Na+/H+ antiport with decreasing pH.

The Na+/H+ antiport is an important regulator of cellular volume, pH and Na+ concentration in mammalian cells. The stoichiometry of this antiporter has previously been shown to be a 1:1 exchange of internal H+ for external Na+. We have investigated this stoichiometry in human leucocytes by using a novel intracellular pH-clamping technique and measuring 22Na+ influx and H+ efflux in the same cells. As internal pH was lowered, the stoichiometry of H+/Na+ exchange rose to a mean +/- S.D. of 2.23 +/- 0.69. This mechanism allows a higher H+ efflux in the face of intracellular acid stress without causing excessive intracellular Na+ overload.

Carrier Proteins↗
PubMed1989

Intracellular pH clamping of human leucocytes: a technique for determination of cellular buffering power and Na+/H+ antiport characteristics.

1. A modified method is described for holding the intracellular pH of leucocytes at different values for prolonged periods of time. 2. Using ammonium sulphate at a final concentration of 8 mmol/l, the buffering power of leucocytes was measured at different internal pH values. 3. A marked dependence of buffering power on internal pH was found. As internal pH was lowered below 7.0, buffering power rose steeply. Above this value, buffering power remained approximately constant. This property may be one factor preventing intracellular acidosis under stress. 4. This method is also suitable for the study of Na+/H+ antiport activity. The addition of external Na+ to cells acid-loaded to an internal pH of 6.7 led to an ethyl isopropyl amiloride-sensitive 1:1 stoichiometric exchange of external Na+ for internal H+.

Biological Transport↗
PubMed1989

The effect of environmental temperature on prandial changes in leucocyte sodium transport in man.

Cellular sodium transport via the Na+, K+-ATPase contributes significantly to daily energy expenditure. The effect of a meal on leucocyte Na+ transport and intracellular electrolytes was therefore investigated in lean normal subjects at room temperatures of 23 degrees and 33 degrees, to determine if the Na pump responds to the need for thermogenesis. In the fasting state, the ouabain-sensitive efflux rate which reflects active Na+ transport, and the intracellular electrolytes were similar. At 2 h after eating a 4.2 MJ (1000 kcal) meal, the ouabain-sensitive efflux rate constant rose when the room temperature was 23 degrees but not at 33 degrees. The ouabain-sensitive Na+ efflux rate, an index of active Na+ transport, rose post-prandially at 23 degrees only. The post-prandial activation of leucocyte active Na efflux in normal subjects was blunted at higher environmental temperatures, when the need for thermogenesis was reduced.

Adult↗
PubMed1989

Leucocyte intracellular pH and Na+/H+ antiport activity in human hypertension.

Hypertension is associated with thickening of the wall of resistance vessels, but the cellular or genetic basis of this is unclear. Cell proliferation and intracellular alkalinization via increased Na+/H+ exchange are linked in the response of tissues to growth factors. To define a possible cellular basis for vascular medial thickening in hypertension, we studied leucocyte intracellular pH, buffering power and Na+/H+ antiport activity in 17 hypertensive and 17 age-, sex- and weight-matched normotensive subjects. The cells from hypertensive subjects were significantly more alkaline [median (range): 7.49 (7.26-7.95) versus 7.39 (7.25-7.53); P less than 0.01], and had a lower buffering power [8.95 (3.05-17.98) versus 12.57 (7.44-19.95) mmol/l per pH unit; P less than 0.02] than those from normotensive subjects. Moreover, the activity of the Na+/H+ antiport was higher when cells were acid-loaded to an intracellular pH of 6.7. The presence of a similar increased activity in vascular smooth muscle cells may be associated with increased cellular proliferation resulting in a thickened media or increased vascular smooth muscle contractility.

Adult↗
PubMed1989

Leucocyte sodium content and sodium pump activity in overweight and lean hypertensives.

Leucocyte sodium content and sodium pump activity was studied in overweight and lean hypertensive subjects and normotensive controls, all in the fasting state. In lean subjects (body mass index less than 27 kg m-2), hypertensives did not have altered leucocyte sodium content or pump activity. In the overweight (mostly obese) subjects, the leucocyte sodium content was higher in hypertensive than in normotensive subjects (median (range) 56.1 (42.0-84.1) vs 32.0 (18.2-59.4) mmol kg-1, P less than 0.001). This raised sodium content in overweight hypertensives was associated with a lower (ouabain-sensitive) 22Na efflux rate constant (2.25 (1.15-3.01) vs 2.64 (1.98-3.61) h-1, P less than 0.05) and a higher passive (or ouabain-insensitive) 22Na efflux rate constant (0.90(0.53-1.18) vs 0.63 (0.21-1.09) h-1, P less than 0.01). The systolic and diastolic blood pressures were significantly correlated to intracellular Na+ in the overweight group (r = 0.41 and 0.56, P less than 0.02 and 0.001 respectively). Thus, hypertension in the overweight subjects is associated with accumulation of intracellular sodium that may be due to abnormalities of the active sodium pump, though changes in ouabain-insensitive mechanisms also occur.

Biological Transport↗
PubMed1989

The derivation of a minimal model insulin sensitivity index from euglycaemic clamps in man.

We describe a computer program based on the minimal model of Bergman et al., which has been used to control euglycaemic hyperinsulinaemic clamps and to derive the insulin sensitivity index (Si) from clamp data. Clamps were undertaken on 33 subjects with a range of insulin resistance. The steady state glucose had an acceptable coefficient of variation (c.v.) and was close to the desired clamp level. The c.v. of the steady state glucose infusion rate was smaller than for other clamp programmes. The Si was correlated with metabolic clearance rate for glucose (MCR) divided by the change in insulin concentration. Our results suggest that the assumptions of the minimal model hold true in the euglycaemic hyper-insulinaemic situation and demonstrate that a minimal-model-derived program can achieve acceptable clamping.

Algorithms↗
PubMed1989

Glycaemic control affects cellular sodium metabolism.

Total and amiloride sensitive leucocyte sodium influx in Media containing 10 mmol/l Na was studied directly using a triple isotope method for measuring initial 22Na uptake rates in 25 non insulin dependent diabetic subjects. Glycaemic control was assessed by glycated haemoglobin and fasting blood glucose. Although no significant relationship between Na flux and either plasma insulin or blood glucose could be found, glycated haemoglobin was significantly correlated with both total and amiloride sensitive flux. Glycaemic control must be considered in future work on cellular sodium metabolism.

Amiloride↗
PubMed1988

Leucocyte sodium efflux and electrolyte content in insulin treated diabetes.

Leucocyte sodium efflux and sodium content were studied in 41 insulin treated diabetic patients and compared to 41 age, body mass index and blood pressure matched nondiabetic control subjects. Fasting leucocyte 22Na ouabain-sensitive efflux rate constants were lower in diabetic patients (median [range] 2.30 [1.04-3.73] versus 2.45 [1.57-3.95] h-1, p less than 0.4) suggesting a reduced sodium pump activity. The 22Na ouabain-insensitive efflux rate constant which reflects passive sodium efflux was raised in insulin treated diabetes (0.92 [0.42-1.73] versus 0.79 [0.28-1.49] h-1, p less than 0.01). Leucocyte sodium content was raised in the diabetic patients (47.7 [26.9-93.4] versus 26.5 [15.9-67.7] mmol/kg, p less than 0.0001). Abnormal cellular sodium handling could lead to hypertension or other complications in diabetes.

Adult↗
PubMed1988

Sodium influx in human leucocytes: a novel technique for assessment of sodium-proton antiport activity.

1. A triple-isotope method for measuring initial 22Na uptake rates in unactivated human leucocytes in the presence of serum, using 3H2O, [14C]sucrose and 22Na, is described. 2. This 22Na influx is inhibited by amiloride, with half-maximal inhibition at a concentration of 10(-5) mol/l. 3. About 70% of the 22Na influx in normal human leucocytes is inhibited by 1 mmol/l amiloride, with an external Na+ concentration of 10 mmol/l. 4. External Na+ antagonizes this inhibition by amiloride. The Km for external Na+ is 9 mmol/l. 5. Intracellular acidification from either external Na+ depletion or ammonium chloride incubation leads to an activation of amiloride-sensitive Na+ influx. 6. The amiloride-sensitive Na+-H+ antiport provides the major influx pathway for Na+ in unactivated human leucocytes in the presence of serum.

Amiloride↗
PubMed1988

Mechanisms of leucocyte sodium influx in essential hypertension.

1. Leucocyte Na+ influx in media containing 10 mmol/l Na+ was studied directly using a triple-isotope method for measuring initial 22Na uptake rates in 20 normal and 18 untreated hypertensive subjects. The effects of 1 mmol/l amiloride (a Na+-H+-antiport inhibitor) and 0.1 mmol/l bumetanide (a Na+,K+,Cl-symport inhibitor) were also examined. 2. The total, amiloride-sensitive and bumetanide-sensitive influx rates were raised in hypertensive compared with normotensive subjects [median (range): total 0.63 (0.25-1.82) vs 0.40 (0.09-0.65) mmol min-1 l-1, P less than 0.002; amiloride-sensitive 0.43 (0.18-1.56) vs 0.26 (0.04-0.48) mmol min-1 l-1, P less than 0.002; bumetanide-sensitive 0.12 (-0.03 to 0.83) vs 0.02 (-0.25 to 0.21) mmol min-1 l-1, P less than 0.005]. 3. We conclude that hypertensive patients have a raised leucocyte total Na+ influx when measured in media containing 10 mmol/l Na+ and that this is contributed mainly by amiloride-sensitive and bumetanide-sensitive Na+ influx mechanisms.

Amiloride↗
PubMed1988

The effect of Intralipid infusion on the human leucocyte sodium-pump in vivo.

1. The effect of unsaturated long-chain non-esterified fatty acids (NEFA) on the human leucocyte sodium-pump was studied in vivo. 2. Plasma NEFA level was raised acutely from 0.28 (SD 0.10) to 2.54 (SD 0.48) mmol/l by infusion of 'Intralipid 20%' (trademark) at 90 ml/h with heparin, and the human leucocyte 22Na efflux rate constants were studied in eight normal weight males. 3. After 3 h, there was a significant lowering of the total (from 3.97 (SD 0.92) to 3.10 (SD 0.71)/h; P less than 0.01) and ouabain-sensitive 22Na efflux rate constants (from 2.89 (SD 0.55) to 2.37 (SD 0.62)/h; P less than 0.02). Ouabain-insensitive efflux rate constants showed a tendency to fall (from 1.08 (SD 0.51) to 0.73 (SD 0.23)/h). Leucocyte potassium content remained unchanged, but sodium content rose from 31 (SD 12) to 38 (SD 18) mmol/kg dry weight (P less than 0.05). Total, ouabain-insensitive and ouabain-sensitive efflux rates did not change significantly during the Intralipid-heparin infusion. 4. Plasma insulin levels rose gradually throughout the 3 h infusion period. 5. In conclusion, NEFA, when raised to pathological levels, can inhibit the leucocyte Na-pump in vivo even in the presence of physiological levels of serum albumin, and may increase insulin secretion.

Biological Transport, Active↗
PubMed1988

Acanthosis nigricans, insulin resistance and cutaneous virilism.

Thirteen patients with the syndrome of acanthosis nigricans and insulin resistance are described. They all had a combination of dermatoses related to hyperandrogenism (cutaneous virilism): hirsuties (II), acne vulgaris (6), hidradenitis suppurativa (5) and androgenic alopecia (4). In addition, 9 out of 13 had keratosis pilaris. The patients had raised fasting plasma insulin levels compared with matched normal controls (P less than 0.01) and increased insulin resistance (P less than 0.02). Insulin resistance correlated with total serum testosterone (rs = 0.65; P less than 0.02).

Acanthosis Nigricans↗