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 x 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.

Hypokalemia, high erythrocyte Na+ and low erythrocyte Na,K-ATPase in relatives of patients dying from sudden unexplained death syndrome in north-east Thailand and in survivors from near-fatal attacks.

The sudden unexplained death syndrome (SUDS) is a sudden death of unknown cause in healthy South-East Asians. In Thailand, it is common in the North-East region. We previously reported high incidences of low erythrocyte sodium and potassium-activated adenosine triphosphatase (Na,K-ATPase) activity and of high erythrocyte sodium in North-East Thais and speculated that this metabolic defect might be associated with the high incidence of SUDS in that region. In this communication, we studied plasma sodium and potassium, erythrocyte sodium and potassium, activities of erythrocyte Na,K-ATPase, ouabain-insensitive ATPase and total ATPase in healthy Thai blood donors from Central Thailand (group 1), healthy North-East city dwellers (group 2), relatives of SUDS victims (group 3) and survivors from SUDS-like attacks (group 4). Compared with groups 1 and 2, group 3 and 4 subjects had significantly lower plasma potassium (p < 0.0001), higher erythrocyte sodium (p < 0.0001), lower activities of erythrocyte Na,K-ATPase (p < 0.0001) and of erythrocyte total ATPase (p < 0.0001). In addition, group 4 subjects had lower plasma potassium, higher erythrocyte sodium and lower activity of total ATPase than those of group 3. The findings suggest that the pathogenesis of SUDS could be related to hypokalemia and a membrane sodium/potassium pump defect.

Hypouricemia, hypokalemia, proximal and distal tubular acidification defect following administration of outdated tetracycline: a case report.

A Thai female patient developed muscular weakness, hypouricemia, hypokalemia and hyperchloremic metabolic acidosis after taking outdated tetracycline. A pathophysiologic study shows a proximal tubular defect for reabsorption of urate and bicarbonate and a distal tubular acidification defect, probably caused by outdated tetracycline.

Abnormal erythrocyte Na, K-ATPase activity in a northeastern Thai population.

We studied the cellular membrane enzyme responsible for potassium transport in different Thai populations. We measured plasma and intraerythrocytic concentrations of sodium and potassium, activities of erythrocytic membrane Na, K-activated adenosine triphosphatase (Na, K-ATPase), ouabain-insensitive ATPase, total ATPase and the activity ratio of Na, K-ATPase/total ATPase in 25 healthy blood donors at Khon Kaen University Hospital, Khon Kaen (group 1), and in 32 donors at the National Blood Center, Thai Red Cross Society, Bangkok (group 2). Group 1 subjects had significantly higher concentrations of erythrocyte sodium (p < 0.001) and lower activity of Na, K-ATPase (p < 0.001) than group 2. When data of these 2 groups were combined, erythrocyte Na+ correlated inversely with Na, K-ATPase and the activity ratio of Na, K-ATPase/total ATPase. Our study suggests that there is a defect in membrane transport enzymes for sodium/potassium in certain northeast Thai populations.

Effects of acute arginine loading on renal and systemic hemodynamics in dogs.

Effects of L-arginine (ARG) infusion on renal and systemic hemodynamics were studied in 12 anesthetized dogs. The experiment was performed in two groups of dogs. The dogs of group 1 (n = 6) received intravenous ARG at 2.5 mmol/kg followed by indomethacin (IND) injection (10 mg/kg) and were rechallenged with ARG at the same amount. The dogs of group 2 (n = 6) received intravenous ARG at 5 mmol/kg followed by IND injection (10 mg/kg) and were later infused with ARG at the same dose. In group 1, the first ARG infusion caused no significant changes in renal and systemic hemodynamics. During the second ARG infusion, glomerular filtration rate (GFR) and renal plasma flow (RPF) were significantly increased when compared with the IND-treated period. In group 2, the first ARG infusion increased cardiac output (CO) and decreased total peripheral resistance (TPR) without significant changes in GFR and RPF. The second ARG infusion induced acute rise of both GFR and RPF approximately twofold, compared with the IND-treated period. CO was also increased significantly. Plasma glucagon levels determined in 2 dogs showed an increase following both ARG infusions. These results indicate that an acute ARG loading induces renal and systemic vasodilatation in a dose-dependent manner despite IND effect, and would indicate that increased renal hemodynamics are not prostaglandin-mediated.

Identification of urinary metabolites and quantitative measurement of creatinine by a proton nuclear magnetic resonance spectrometry.

1H-NMR spectra of 60 human urine specimens were recorded without pretreatment by a JEOL FX 90 Q spectrometer operating at 89.55 MHz. The signals of the methyl protons of creatinine (3.04 +/- 0.02 ppm) were observed in all spot fasting morning urine samples collected from 7 healthy persons, 10 patients with nephrotic syndrome and 43 patients with diabetes mellitus. The concentrations of creatinine measured by NMR spectroscopy (Y) and the chemical assay based on the Jaffe reaction (X), over the range of 19-190 mg/dl, were compared by the least-squares linear regression analysis (Y = 6.7799 + 0.6717 X). The mean urinary creatinine concentration by NMR spectroscopy appeared to be lower than that obtained by the Jaffe reaction at the normal and high normal levels. In the urine of 20 diabetic patients with an average blood glucose of 251.30 +/- 50.26 (SD) mg/dl typical spectra of the multiple large signals of glucose protons at position from 3.13 +/- 0.04 to 4.04 +/- 0.12 (SD) ppm were shown. Moreover, some urinary metabolites and amino acids spectra were occasionally detected at one time.