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Biomedical subjects

L Longerich

Publications and source records attributed to L Longerich.

At least 37 records · Page 2Linked to original sources
PubMed1993

Ethanol induced hypertension in rats: reversibility and role of intracellular cytosolic calcium.

This study examined the reversibility of chronic ethanol induced increase in systolic blood pressure, elevated platelet cytosolic free calcium and aortic calcium uptake in rats and the effect of a calcium channel blocker on these changes. Twenty-four male Wistar-Kyoto rats, age 7 weeks, were divided into 4 groups of 6 animals each. Animals in group I were given water and group II, III and IV, 5% ethanol in drinking water for the next 7 weeks. Systolic blood pressure in the ethanol treated rats was significantly higher (p < 0.01) than in controls after 1 week and remained higher. After 7 weeks, group I was continued on water, group II on ethanol, group III was continued on ethanol but with the addition of verapamil 5 mg/100 ml in their drinking water and group IV was returned to normal drinking water for the next 7 weeks. After 14 weeks, systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake was significantly higher (p < 0.01) in rats given ethanol for 14 weeks and also in rats given ethanol for 7 weeks followed by water for 7 weeks as compared to controls. These two groups also showed smooth muscle cell hyperplasia with some thickening of the wall and narrowing of the lumen in small arteries and arterioles of kidney. Verapamil given to the ethanol treated rats normalized their blood pressure, platelet cytosolic free calcium, aortic calcium uptake and attenuated renal vascular changes. Discontinuation of ethanol treatment for 7 weeks did not reverse the hypertension or the adverse renal vascular changes in ethanol induced hypertensive rats.

Alcoholism↗
PubMed1992

Heparin, fatty acids and sodium, potassium-ATPase inhibition by plasma factors during hemodialysis.

To assess the relationship between heparin and the associated increase in nonesterified fatty acids (NEFA) and their possible influence on Na,K-ATPase during hemodialysis, we studied two groups of patients: (1) 12 patients on chronic hemodialysis dialysed with heparin and (2) 6 patients dialysed without heparin. All 12 patients who received heparin anticoagulation had a 7-fold rise in NEFA on average and also had an increase in circulating inhibitors of Na,K-ATPase assayed by 3H-ouabain displacement from Na,K-ATPase and/or by effect of plasma on the uptake of 86Rb by rat aortic rings. Serial assays in 3 of the patients receiving heparin showed NEFA and inhibitory changes to be at or near maximum within 30-60 min. Of the individual NEFA, the greatest relative increases were in oleic (18:1) and linoleic (18:2) acids, and the strongest correlations were between linoleic acid and both 3H-ouabain displacement (r = 0.94) and 86Rb uptake (r = 0.86). However, a small and slower increase in NEFA also occurred in 3 of the patients dialysed without heparin. We conclude that heparin anticoagulation during dialysis leads to a rapid and marked increase in circulating NEFA, particularly the unsaturated fatty acids, with a corresponding interference with Na,K-ATPase activity. The clinical significance of these findings is unknown. The rise in NEFA during dialysis without heparin in some patients suggests that factors other than heparin may also contribute to the rise in NEFA.

Adult↗
PubMed1992

Oral heparin prevents hypertension and elevated cytosolic calcium in salt-sensitive rats.

This study examined the effect of oral heparin on systolic blood pressure, platelet cytosolic free calcium, aortic calcium uptake and renal vascular changes in Dahl salt-sensitive (DS) rats on low (0.4% NaCl) and high (8% NaCl) salt diet. Twenty-four male DS rats, age 8 weeks, were divided into four groups of 6 animals each. Groups I and II were on low salt diet and groups III and IV on the high salt diet. Additionally, groups I and III were placed on 100% H2O and groups II and IV on sodium heparin 0.5 mg/ml in H2O as their drinking water for a period of 6 weeks. At 14 weeks, systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake were significantly higher in rats on high salt diet and water compared with rats from all other groups. Oral heparin treatment prevented the increase in systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake in rats on high salt diet. Heparin also prevented or attenuated the onset of adverse renal vascular changes observed in Dahl salt-sensitive rats on high salt diet. Oral heparin treatment did not cause abnormal hematological, biochemical or pathological changes in rats.

Animals↗
PubMed1992

Oral heparin normalizes blood pressure and elevated cytosolic calcium in hypertensive rats.

Increased calcium uptake in vascular tissue, leading to elevated cytosolic free calcium has been implicated in the pathophysiology of hypertension. This study examined the effect of oral heparin on systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake in spontaneously hypertensive and normotensive Wistar-Kyoto rats. Starting at age 12 weeks, each strain of rats were divided into 2 groups (6 animals in each group); the control group was placed on H2O (100%) and the experimental group was placed on H2O with heparin (0.5 mg sodium heparin/ml H2O) for a period of nine weeks. At 21 weeks, systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake were significantly higher in spontaneously hypertensive rats on water compared with spontaneously hypertensive rats on heparin and Wistar-Kyoto rats on water and on heparin. Oral heparin treatment normalized the elevated platelet cytosolic free calcium, aortic calcium uptake and systolic blood pressure in spontaneously hypertensive rats but had no effect on Wistar-Kyoto rats. Heparin also prevented onset of adverse renal vascular changes observed in spontaneously hypertensive rats. Oral heparin treatment did not cause abnormal hematological, biochemical or pathological changes in rats.

Administration, Oral↗
PubMed1991

Deuterium oxide prevents hypertension and elevated cytosolic calcium in hypertensive rats.

Increased calcium uptake in vascular tissue, leading to elevated cytosolic free calcium, has been implicated in the pathophysiology of hypertension. This study examined the dose-dependent effect of deuterium oxide (5%, 10%, or 20% in drinking water) on systolic blood pressure, aortic calcium uptake, and platelet cytosolic free calcium in spontaneously hypertensive rats. Starting at age 8 weeks, spontaneously hypertensive rats were divided into four groups of six animals each. The drinking water of groups 1, 2, 3, and 4 was replaced by 100% water and 5%, 10%, and 20% deuterium oxide in water, respectively, for another 7 weeks. Ten Wistar-Kyoto rats, age 8 weeks, were given 100% water for the next 7 weeks. The usual increase in systolic blood pressure and the associated increase in aortic calcium uptake and platelet cytosolic free calcium in spontaneously hypertensive rats at age 15 weeks was lowered in a dose-dependent manner by deuterium oxide. Deuterium oxide also prevented renal vascular changes in spontaneously hypertensive rats. A minimum dose of 10% deuterium oxide was needed to completely prevent the development of hypertension, elevated aortic calcium uptake, platelet cytosolic free calcium, and renal vascular changes in spontaneously hypertensive rats.

Animals↗
PubMed1990

Comparison of urinary tract infection in calcium oxalate and calcium phosphate stone formers.

To compare the frequency of urine infection in calcium oxalate and calcium phosphate stone formers, we reviewed charts from patients whose last renal stone submitted for analysis was predominantly composed of calcium phosphate in 118 and of calcium oxalate in 223. Positive cultures were commoner, but not significantly, in the phosphate than the oxalate stone formers, both in men (17 vs. 7.6%) and women (22 vs. 15%). Bacteria frequently producing urease were found in only 4% of the phosphate group. Urine leucocytes were slightly more frequent in the oxalate group for men and significantly so for women. The results do not support the concept that calcium phosphate stones are mainly due to infection with urease-producing or other bacteria.

Calcium Oxalate↗
PubMed1990

Plasma conjugated androgens in a dialysis-dependent male as immunoreactive digitalis-like factors.

Endogenous digitalis-like factors (DLF) including those which were immunoreactive with digoxin antibody and those which displaced ouabain from Na,K-ATPase, were isolated from the plasma of a dialysis-dependent male patient not taking digoxin. Plasma was passed through a C18 disposable column, the DLF eluted with methanol and separated by HPLC on a C8 column. Immunoreactive DLF were measured in each 1 ml HPLC fraction using radioimmunoassay (RIA) for digoxin. The immunoreactive peaks were determined and aliquots from each peak analyzed by fast atom bombardment mass spectroscopy (FAB-ms). The compounds in the five major HPLC immunoreactive peaks were identified as: 1) dehydroepiandrosterone glucuronide and tetrahydrocortisone glucuronide; 2) epiandrosterone glucuronide; 3) dehydroepiandrosterone sulfate and androsterone glucuronide; 4) epiandrosterone sulfate and 5) androsterone sulfate and androstanediol glucuronide. These immunoreactive DLF represent 70% of the total plasma immunoreactive DLF of 0.124 micrograms digoxin equivalents/l. Aliquots of the HPLC fractions were also assayed for ability to displace ouabain from Na,K-ATPase. The ouabain displacing DLF gave a very different elution pattern from that obtained by RIA with the major Na,K-ATPase ouabain displacing DLF eluting in the more polar fractions. They remain unidentified.

Adult↗
PubMed1989

Lipids as endogenous Na,K-ATPase inhibitors in plasma of healthy individuals and in dialysis dependent patients.

We assayed plasma Na,K-ATPase inhibitory activity due to total lipids and lipid fractions. The effect of dialysis on the Na,K-ATPase inhibitory activity was also studied. Plasma lipid extracts from 11 healthy volunteers and 9 dialysis-dependent patients (pre and post dialysis) were separated into neutral lipids and phospholipids. Further fractionation was by thin layer chromatography. These lipid fractions were analyzed for Na,K-ATPase inhibitory activity by displacement of [3H]-ouabain from hog brain Na,K-ATPase. Total inhibitory activity was significantly increased (p less than 0.001) in the post-dialysis plasma compared to pre-dialysis plasma of the same patient group and to controls (482, 85 and 78 nmol/L respectively; means of the groups in digoxin equivalents). The major inhibitory activity was associated with non-esterified fatty acids with modest contributions from four other lipid fractions. Our results show that endogenous lipids are major plasma Na,K-ATPase inhibitors in vitro under these assay conditions.

Adult↗
PubMed1988

Identification of progesterone and cortisol as immunoreactive plasma digitalis like factors in pregnancy.

Plasma values for immunoreactive digitalis like factors (DLF) in 3 women during the third trimester of pregnancy were 0.13, 0.13 and 0.40 ng digoxin equivalents/ml. Progesterone accounted for 39%, 35% and 19% of the total DLF in the three women respectively, and cortisol 4%, 18% and 7% based on HPLC analysis. Both progesterone and cortisol displaced [125I]-digoxin from digoxin antibody and [3H]-ouabain from hog brain Na,K-ATPase in a concentration-dependent manner, but only progesterone in the plasma concentrations found in these patients would appreciable influence Na,K-ATPase. HPLC separation of the plasma DLF from two of the women showed several peaks. Two of these were identified as progesterone and cortisol by retention time, immunoassay and by GC-mass spectrometry.

Blood Proteins↗
PubMed1988

Disposable-column radioimmunoassay for serum digoxin with less interference from metabolites and endogenous digitalis-like factors.

A preparative extraction step using disposable C18 low-pressure chromatography columns greatly improved the specificity of a commercially prepared digoxin radioimmunoassay (RIA). Elution solvents were isopropanol/water (15/85 by vol), which extracted most immunoreactive digitalis-like factors and metabolites, and methanol, which extracted digoxin for RIA. Many different digoxin RIA kits could be used. The coefficients of variation for replicates and duplicates were 4.6% and 5.2%. Analytical recoveries of digoxin standards in serum of 1.0, 0.5, and 0.1 microgram/L were 96%, 95%, and 88%, respectively. Serum digoxin was assayed by this method in 200 patients, 47 of whom were studied by HPLC-RIA. Values correlated better with "true digoxin" by HPLC-RIA (r = 0.93) than did values found by direct assay (r = 0.63). The mean for the isopropanol fraction as a percentage of the mean direct RIA value was higher for the 21 dialysis-dependent patients than was that found for the 179 nondialysis patients (P less than 0.004). The method is suggested as being most useful when metabolites or digitalis-like factors are known to be often high and values for digoxin are disproportionate to the dose.

1-Propanol↗
PubMed1988

Evidence for an adrenal contribution to plasma digitalis-like factors.

Digitalis-like factors (DLF) were assayed on plasma collected serially using antibody to digoxin: (1) after intravenous ACTH (n = 3 patients) and (2) after 0.15 U/kg crystalline insulin, 50 micrograms gonadotropin-releasing hormone and 0.2 mg thyrotropin-releasing hormone (n = 7) as a combined pituitary function test. Patients had either hypothalamic-pituitary or ovarian problems. Mean values for DLF rose fourfold after ACTH, and by a factor of 2.3 with the combined pituitary function test. DLF rose at least 50% in all 10 subjects. In 3 dogs, adrenal vein values for DLF were on average more than double values in either adrenal artery or lower vena cava. These results suggest that certain DLFs have an adrenal origin.

Adrenal Glands↗
PubMed1987

Plasma endogenous digitalis-like factors in healthy individuals and in dialysis-dependent and kidney transplant patients.

Plasma digitalis-like factors (DLF), dehydroepiandrosterone sulfate (DHEAS) and cortisol were assayed in 20 healthy subjects, 22 dialysis dependent subjects and 30 patients with kidney transplants. DLF were assayed on plasma extracts by digoxin radioimmunoassay (RIA), and by Na,K-ATPase inhibition and [3H]-ouabain displacement using hogbrain Na,K-ATPase. Values for the 3 methods strongly intercorrelated (r = 0.99, p less than .001). Mean values for plasma DLF, assayed by all three methods, were significantly greater in dialysis dependent subjects, than in healthy subjects (p less than .0001). Mean plasma DLF values measured by digoxin RIA in renal transplant recipients, were significantly lower than in dialysis dependent subjects (p less than 0.0001) and higher than in healthy subjects. Plasma DLF values correlated inversely with creatinine clearance (p less than 0.01). Plasma DHEAS levels were significantly lower and contributed substantially less to digoxin antibody reactivity and ouabain displacement in dialysis subjects and in renal transplants compared with healthy subjects. There was no change in plasma immunoreactive DLF, DHEAS or cortisol measured before and after dialysis. DHEAS is a major digoxin like immunoreactive DLF and a minor Na,K-ATPase inhibitor in healthy subjects but makes only a minor contribution to DLF in dialysis and transplant subjects. We found the assays involving Na,K-ATPase inhibition and [3H]-ouabain displacement from Na,K-ATPase to be more sensitive for plasma DLF than the digoxin RIA, but because of the strong correlation between the methods, we suggest the RIA on plasma extracts can be used as a screening procedure.

Adult↗
PubMed1986

Interpretation of serum digoxin values in renal failure.

We have studied three circumstances that have been reported to make interpretation of the serum digoxin concentration difficult in patients with renal failure: increased biotransformation; endogenous digitalis-like factors (DLF); and sudden, unexpected increases in serum digoxin values, even after the discontinuation of digoxin. Biotransformation, as estimated by the percent true digoxin in serum, was comparable in patients with renal failure who were dependent on dialysis and in control subjects (76% vs. 73%). Certain commercial immunoassays did not, or rarely, gave values for DLF of clinical significance (greater than 0.2 ng/ml digoxin equivalents) in patients with a wide range of renal dysfunction who were not receiving digoxin. With a sensitive method, values for DLF did not exceed 0.23 ng/ml in 22 dialysis patients dependent on dialysis, but were significantly increased in comparison with values in control subjects. The case histories of two patients with renal failure, acute illness, and sudden unexpected marked increases in serum digoxin concentrations are presented and possible explanations are discussed.

Adult↗
PubMed1985

Dehydroepiandrosterone sulfate as a digitalis like factor in plasma of healthy human adults.

Plasma values for digitalis like factors (DLF) and dehydroepiandrosterone sulfate (DHEA-S) in 11 healthy adults were (mean +/- SD) 44 +/- 6 pmol digoxin equivalents/L and 11 +/- 3 mumol/L respectively. DHEA-S accounted for 62-100% of the total plasma DLF. DHEA-S and plasma DLF displaced [125I]digoxin from digoxin antibody, inhibited hog brain Na,K-ATPase and displaced [3H]ouabain from ATPase in a concentration dependent manner similar to digoxin. Plasma extracts (11 subjects) inhibited Na,K-ATPase and displaced [3H]ouabain from Na,K-ATPase with mean values +/- SD of 1.7 +/- 0.22 and 1.8 +/- 0.25 nmol digoxin equivalents/L plasma respectively. HPLC fractionation of plasma DLF showed several peaks. The major peak was due to DHEA-S, identified by its retention time, radioimmunoassay of DHEA-S and mass spectrometry.

Adult↗
PubMed1985

Combined liquid chromatography/radioimmunoassay with improved specificity for serum digoxin.

This method for assaying digoxin in serum with improved specificity combines small-column extraction of serum, "high-performance" liquid chromatography, and RIA of the eluted fractions. Analytical recoveries of 1.0, 0.5, and 0.1 microgram/L standards were 95%, 93%, and 84%, respectively. The CVs for duplicates and replicates of sera with values of 0.5 to 1 microgram/L were 4 to 6%. Fifty-nine sera from 50 patients receiving digoxin were so studied. All digoxin metabolites appear to cross react with antibody to digoxin to various degrees. The most polar metabolites were quantitatively the most important, their average cross reactivity being 33%. For eight patients the value for digoxin by the present method was less than 60% of the RIA value. Sera from nine patients not taking digoxin but with falsely high digoxin values were also studied by the present method. The digoxin peak was well resolved from those for (a) digoxin metabolites (except dihydrodigoxin), (b) digitalis-like factors in neonates and in patients with renal failure or combined hepatic and renal failure, and (c) two cross reacting drugs and their metabolites.

Adult↗
PubMed1984

Digoxin-rifampin interaction.

Digoxin doses required to maintain therapeutic serum concentrations rose substantially in two patients dependent on dialysis with the commencement of rifampin therapy. When rifampin was discontinued, doses fell to requirements before rifampin. Serum digoxin concentration may fall to ineffective levels with rifampin therapy and rise to potentially toxic levels when rifampin is discontinued.

Digoxin↗