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Biomedical subjects

L Longerich

Publications and source records attributed to L Longerich.

At least 19 recordsLinked to original sources
PubMed1995

Ethanol- and threonine-induced hypertension in rats: a common mechanism.

OBJECTIVE: To investigate the effects of oral L-threonine and ethanol, precursor of endogenous acetaldehyde, on systolic blood pressure, cystolic free calcium ([Ca2+]i) and vascular calcium uptake in Wistar-Kyoto (WKY) rats. METHODS: Twenty-four male WKY rats aged eight weeks were divided into four groups of six animals each. Animals were given either water or 5% ethanol, 8% L-threonine or 8% L-glycine in drinking water for 15 weeks, animals were sacrificed, aortic rings were incubated in physiological buffer containing 45Ca2+ and uptake was measured after 20 mins. ([Ca2+]i in platelets was measured with a fluorescence [Ca2+]i indicator, FURA-2. Tissues were processed for morphological investigation. RESULTS: After 15 weeks, systolic blood pressure, platelet [Ca2+]i and aortic calcium uptake were all significantly higher (P < 0.001) in rats given either threonine or ethanol than in control rats given water or glycine. Animals in threonine or ethanol group also showed smooth muscle cell hyperplasia, with some thickening of the wall and narrowing of the lumen in small arteries and arterioles of the kidney. Glycine treatment did not cause any of these changes in rats. CONCLUSION: These results suggest that acetaldehyde may be a common cause of both ethanol- and threonine-induced hypertension.

Animals↗
PubMed1995

N-acetyl cysteine attenuates ethanol induced hypertension in rats.

All known pathways of ethanol metabolism result in the production of acetaldehyde, a highly reactive compound. N-acetyl cysteine, an analogue of the dietary amino acid cysteine, binds acetaldehyde, thus preventing its damaging effect on physiological proteins. This study examined the effect of oral N-acetyl cysteine on the increased blood pressure, platelet cytosolic free calcium, blood acetaldehyde and adverse renal vascular changes induced by chronic ethanol treatment in rats. Twenty-four male Wistar-Kyoto (WKY) rats, age 7 weeks were divided into four groups of six animals each. Animals in group I were given water and group II 5% ethanol in water for the next 14 weeks. Animals in group III were given 5% ethanol + 1% N-acetyl cysteine for 4 weeks followed by 5% ethanol + 2% N-acetyl cysteine for the next 10 weeks. Animals in group IV were given 5% ethanol for 7 weeks; at that time ethanol was withdrawn and animals were placed on water with 2% N-acetyl cysteine for the next 7 weeks. After 14 weeks systolic blood pressure and platelet cytosolic free calcium were all significantly higher (p<0.001) in rats given ethanol as compared to rats in other groups. N-acetyl cysteine treatment, along with ethanol, significantly (p<0.001) attenuated the increased blood pressure and platelet cytosolic free calcium and adverse renal vascular changes. Discontinuation of ethanol treatment for 7 weeks along with N-acetyl cysteine supplementation also significantly lowered the blood pressure and platelet cytosolic free calcium and attenuated adverse renal vascular changes. There was no significant difference in aortic malonaldehyde among four groups. Increase in blood acetaldehyde with ethanol treatment was significantly attenuated with N-acetyl cysteine treatment. These results suggest that acetaldehyde may be the cause of ethanol-induced hypertension and elevated cytosolic free calcium and renal vascular changes.

Acetaldehyde↗
PubMed1994

Fructose-induced hypertension, hypertriglyceridemia and elevated cytosolic calcium in rats: prevention by deuterium oxide.

We examined the effect of 5% deuterium oxide (D20) in drinking water on systolic blood pressure, platelet cytosolic free calcium, aortic calcium uptake and plasma insulin, glucose and triglycerides in rats with fructose-induced hypertension. Eighteen male Wistar-Kyoto (WKY) rats, age 8 weeks, were divided into 3 groups of 6 animals each. Animals in group I were given water; group II, 8% fructose and group III, 8% fructose + 5% D20 as their drinking water for the next 15 weeks. Systolic blood pressure in the fructose treated rats was significantly higher (p < 0.01) than in animals on water after 2 weeks and remained higher throughout the study. At 15 weeks, systolic blood pressure, platelet cytosolic calcium, aortic calcium uptake and plasma glucose, insulin and triglycerides were significantly higher (p < 0.01) in the fructose treated rats compared with rats from other groups. Deuterium oxide given together with fructose prevented development of high blood pressure and the associated increase in platelet cytosolic calcium, aortic calcium uptake and plasma triglycerides. D20 treatment did not prevent fructose induced increases in plasma insulin and glucose. The parallel increase in systolic blood pressure, cytosolic free calcium, and in vascular calcium uptake suggests that an increased cytosolic free calcium is involved in the pathophysiology of hypertension. D20 prevents this hypertension by normalizing cytosolic free calcium.

Animals↗
PubMed1994

Oral treatment with low molecular weight heparin normalizes blood pressure 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 low molecular weight heparin (Logiparin) on systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake in spontaneously hypertensive rats. Starting at age 12 weeks, spontaneously hypertensive rats were divided into three groups of six animals each. The drinking water of groups 1, 2 and 3 was replaced by 100% H2O, 0.5 mg (low dose) or 1 mg (high dose) low molecular weight heparin/ml H2O, respectively, for next 11 weeks. Six normotensive Wistar-Kyoto rats (age 12 weeks) on H2O and six on low dose heparin in H2O were used as controls. At age 23 weeks, increase in systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake in spontaneously hypertensive rats was significantly lowered by low dose LMW heparin as compared to spontaneously hypertensive rats on H2O, but was significantly higher than Wistar-Kyoto rats on H2O and LMW heparin. This dose of heparin did not have any effect on these parameters in normotensive Wistar-Kyoto rats. High dose LMW heparin normalized the elevated platelet cytosolic free calcium, aortic calcium uptake and systolic blood pressure in spontaneously hypertensive rats, but it had a limited effect on adverse renal vascular changes. Oral low molecular weight heparin did not cause any abnormal hematological, biochemical or pathological changes in rats.

Administration, Oral↗
PubMed1993

Calcium and calcium magnesium carbonate specimens submitted as urinary tract stones.

Of 8,129 specimens submitted as urinary stones from 6,095 patients, 67 from 15 patients were predominantly calcium carbonate or calcium magnesium carbonate (dolomite) by infrared analysis. Detailed study of 1 man and 4 women who submitted 3 or more such specimens showed that all were of aragonite calcium carbonate crystal form in 2 women and all calcite in the man. All 3 patients had a long history of nephrolithiasis preceding submission of calcium carbonate stones. There was frequent and often painful spontaneous passage of many small stones. Medullary sponge kidney was reported in 2 patients. Specimens submitted by the other 2 women included dolomite and quartz artifacts. Of the other 10 patients 4 had calcite and 1 had aragonite (possibly true stones). Five patients had artifacts with dolomite in 3 and mixed specimens in 2. True calcium carbonate kidney stones and calcium carbonate artifacts may be difficult to distinguish, and dolomite and quartz artifacts may require x-ray diffraction for clear-cut diagnosis.

Adult↗
PubMed1993

Deuterium oxide normalizes blood pressure and elevated cytosolic calcium in rats with ethanol-induced hypertension.

This study examined the effect of 10% deuterium oxide (D2O) in drinking water on systolic blood pressure, platelet cytosolic free calcium, aortic calcium uptake and renal vascular changes in rats with ethanol-induced hypertension. Eighteen male Wistar-Kyoto rats, age seven weeks, were divided into three groups of six animals each. Group I was given water and groups II and III, 5% ethanol in drinking water for the next seven weeks. After one week, systolic blood pressure in the ethanol-treated rats was significantly higher (P < 0.01) than in rats drinking water. After seven weeks, animals in group I were continued on water, group II on 5% ethanol, group III on 5% ethanol but with the addition of 10% D2O in their drinking water for the next seven weeks. After 14 weeks, systolic blood pressure, platelet cytosolic free calcium and aortic calcium uptake was significantly higher (P < 0.01) in group II rats (given ethanol for 14 weeks) compared with rats from other groups. Ethanol-treated rats also showed smooth muscle hyperplasia with some thickening of the wall and narrowing of the lumen in small arteries and arterioles of the kidney. D2O given to ethanol-treated rats normalized their blood pressure, platelet cytosolic free calcium, aortic calcium uptake and attenuated renal vascular changes.

Animals↗
PubMed1993

Digoxin-like factors in herbal teas.

Forty-six commercially packaged teas and 78 teas prepared from purchased herbs were assayed for digoxin-like factors (DLF) by their crossreactivity with digoxin antibody (immuno-crossreactive DLF) and by their inhibition of ouabain binding to membrane Na,K-ATPase (NKA inhibitory DLF). Three packaged teas and 3 herbs gave NKA inhibitory DLF values > 30 micrograms digoxin equivalents/cup. Two packaged teas and 3 herbs gave immuno-crossreactive DLF values > .050 micrograms digoxin equivalent/cup. One herb, pleurisy root, had a crossreactive DLF value of 187 micrograms/cup and NKA inhibitory DLF equivalent to 3658 micrograms/cup. Plasma digoxin-like factors were measured after ingestion of the 3 commercially packaged herbal teas with highest values for NKA inhibitory DLF. After ingestion of each of the 3 teas, plasma NKA inhibitory DLF increase, in one case more than 100-fold. Two teas produced a measurable increase in plasma immuno-crossreactive DLF after ingestion. Some digoxin-like factors in human plasma may have a dietary source.

Beverages↗
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↗