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Biomedical subjects

R M Schaefer

Publications and source records attributed to R M Schaefer.

At least 127 records · Page 7Linked to original sources
PubMed1989

Reduced protein catabolism by the antiglucocorticoid RU 38486 in acutely uremic rats.

Protein breakdown in acute uremia is enhanced, as evidenced by an increment in amino acid release from skeletal muscle and an increased amino acid uptake and urea and glucose production by the liver. To study whether this metabolic pattern is mediated by glucocorticoids, we investigated the effect of the antiglucocorticoid RU 38486 on both muscle protein breakdown and urea and glucose production of isolated hepatocytes in acutely uremic rats. Animals were rendered uremic by bilateral nephrectomy (BNX). Forty-eight hours after BNX, the rats had markedly elevated serum levels of urea nitrogen, creatinine, potassium, and phosphorus. In uremic rats receiving RU 38486 comparable levels of serum creatinine were found, but the serum levels of urea nitrogen (221 +/- 4 vs. 259 +/- 5 mg/dl) and phosphorus (6.5 +/- 0.3 vs. 8.5 +/- 0.4 mmol/liter) were significantly decreased as compared to uremic animals without RU 38486. In comparison to sham operated rats, urea-N appearance (net urea production) was increased by 56% 48 hours after BNX. This increment was almost completely reversed in uremic animals receiving the antiglucocorticoid. In untreated uremic rats, plasma levels of Nt-methylhistidine were 10.3 +/- 0.9 micrograms/dl, whereas the administration of RU 38486 caused a significant decline in the levels of this amino acid (7.6 +/- 0.5 micrograms/dl). Hepatic glucose production in BNX rats was significantly increased from alanine (+174%), glutamine (+158%), and serine (+87%) as compared to sham-operated controls. Concomitantly, hepatic urea formation from amino acid substrates was also enhanced in BNX animals. With the administration of RU 38486 to acutely uremic rats, both hepatic glucose and urea production were normalized.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Clinical evaluation of a new high-flux cellulose acetate membrane.

One major goal of dialysis therapy has become the removal of beta 2-microglobulin (beta 2-m). The interdialytic elimination of beta 2-m was studied using a newly developed high-flux cellulose acetate (CA) membrane. The results show that high-flux CA dialyzers offer better biocompatibility than classical Cuprophan or high-flux Cuprophan devices, with regard to leukopenia, C3a desarg generation, and elastase release from polymorphonuclear (PMN) leukocytes. Compared to high-flux CA membranes, high-flux PMMA membranes induce less C3a desarg formation but comparable leukopenia. High-flux PMMA membranes, however cause greater leukocyte stimulation than CA as demonstrated by more PMN elastase release during hemodialysis. Using high-flux CA or high-flux PMMA membranes, serum beta 2-m levels decreased 32% during dialysis. Serum beta 2-m dropped 10% with high-flux Cuprophan membranes, but remained unchanged with conventional Cuprophan dialyzers. Sieving coefficients for beta 2-microglobulin (beta 2-m) were virtually zero with classical Cuprophan and 0.66 with high-flux cellulose acetate membranes. High-flux membranes made of Cuprophan and PMMA gave coefficients of 0.25 and 0.45, respectively. This indicates the high removal capacity of the new CA-membrane for substances with high molecular weight. This high-flux CA membrane thus appears to combine a good degree of biocompatibility with a high capacity for beta 2-m removal.

Adult↗
PubMed1989

Cadmium and renal hypertension.

In our study we investigated 36 patients with renal disease, 22 of whom were hypertensive. In all proteinuria was present (4.30 +/- 5.05 g protein/day) and renal lesions were proved by renal biopsy. Blood cadmium in non-smokers was significantly (P less than 0.05) lower than in smokers. We found a positive correlation between cadmium concentrations in blood and urine (P less than 0.01, r = 0.44) and between cadmium concentration in blood and serum uric acid levels (P less than 0.01, r = 0.44). Proteinuria was weakly correlated with cadmium concentration in urine (P less than 0.05, r = 0.35). Patients with hypertension showed a significantly higher (P less than 0.05) urine cadmium excretion per day (1.60 +/- 1.12 micrograms/day compared with normotensives with disease of the kidney (1.14 +/- 1.47 micrograms/day). Our results indicate that cadmium may be involved in the development of hypertension in patients with renal disease.

Cadmium↗
PubMed1989

Normalization of serum prolactin levels in hemodialysis patients on recombinant human erythropoietin.

Correction of anemia in long-term hemodialysis patients by recombinant human erythropoietin (r-HuEPO) has been reported to improve sexual function. As elevated serum prolactin levels are believed to contribute to altered sexual function in uremia, we followed serum prolactin and testosterone levels during four months of r-HuEPO therapy. Within these four months, hematocrit values rose from 23.7 +/- 1.2 to 35.7 +/- 0.2% and hemoglobin from 7.3 +/- 0.3 to 11.3 +/- 0.4 g/100 ml. In parallel, serum prolactin values decreased significantly, from 66.9 +/- 9.3 to 9.6 +/- 2.6 ng/ml in females and from 39.5 +/- 10.5 to 10.3 +/- 1.0 ng/ml in male dialysis patients. Testosterone concentrations were in the lower normal range in male patients and remained unchanged during r-HuEPO therapy. Sexual function improved in four out of seven males, and five out of nine female patients started to have regular menstruations again. It appears that treatment of anemia in end-stage renal disease by r-HuEPO may improve sexual function by lowering elevated serum prolactin concentrations.

Adult↗
PubMed1989

Improved sexual function in hemodialysis patients on recombinant erythropoietin: a possible role for prolactin.

As it was reported that correction of anemia in long-term hemodialysis patients by recombinant human erythropoietin (r-HuEPO) is associated with improved sexual function, we conducted the present study to further delineate the mechanism(s) by which this is brought about. Serum prolactin, testosterone, and parathyroid hormone (PTH) levels were followed during 4 months of r-HuEPO therapy. Within 4 months of treatment with r-HuEPO, hematocrit values rose from 23.7 +/- 1.2 to 35.7 +/- 0.2% and hemoglobin increased from 7.3 +/- 0.3 to 11.3 +/- 0.4 g/100 ml. In parallel, serum prolactin values decreased significantly from 66.9 +/- 9.3 to 9.6 +/- 2.6 ng/ml in females and from 39.5 +/- 10.5 to 10.3 +/- 1.0 ng/ml in male dialysis patients. Testosterone concentrations were low in male patients and remained unchanged during r-HuEPO therapy. Baseline PTH values were elevated (1,880 +/- 220 pg/ml) in patients of both sexes and declined to 1,410 +/- 180 pg/ml during treatment with r-HuEPO. However, this difference did not reach statistical significance. Sexual function improved in 4 out of 7 males and 5 out of 9 female patients began to menstruate regularly again. It appears that treatment of anemia in end-stage renal disease by r-HuEPO improves sexual function via normalization of elevated serum prolactin concentrations.

Adult↗
PubMed1988

Abnormalities of carbohydrate metabolism in spontaneously hypertensive rats.

The present study was performed to investigate as to whether peripheral insulin resistance exists in spontaneously hypertensive rats (SHR). After a 12 h fasting period, SHR had significantly higher serum glucose and higher plasma glucagon values in comparison to normotensive control rats (WKY). There was a tendency for higher serum insulin concentrations as well, but this difference did not reach significance. After oral glucose loading or glucose/insulin administration, serum glucose and insulin levels were also higher in SHR compared to WKY rats. Muscle glycogen and glucose concentrations were identical in fasted SHR and WKY rats. With an oral glucose load or glucose/insulin treatment there was a significant increase in muscle glycogen, whereas glucose values declined in skeletal muscle. Both total (a+b-form) phosphorylase activity as well as the active a-form of the enzyme were similar in skeletal muscle of SHR and WKY rats. Glucose/insulin administration or oral glucose loading induced a considerable reduction of both a+b-form and a-form activities. The decrease in muscle phosphorylase activities was almost identical in both groups of animals. There was also a comparable activity of muscle glycogen synthetase activity in all groups of rats. Despite subtile changes of glucose, glucagon and to a lesser degree insulin levels which would be suggestive of insulin resistance, the data obtained from skeletal muscle argue against peripheral insulin resistance in spontaneously hypertensive rats.

Animals↗
PubMed1988

[Therapy of renal anemia with recombinant human erythropoietin].

The effectiveness of recombinant human erythropoietin (r-HEPO) was tested in 15 haemodialysis patients. The dosage was started at 24 IU/kg three times weekly, as an intravenous bolus at the end of the dialysis session, and then doubled every two weeks as long as the rise in haemoglobin was less than 2 g/dl. During treatment the reticulocyte count rose from 31 +/- 5 x 10(3)/microliters to 152 +/- 11 x 10(3)/microliters after 16 weeks. The haematocrit rose from 0.24 +/- 0.01 to 0.36 +/- 0.002. At the beginning of treatment the haemoglobin level was 7.3 +/- 0.3 g/dl and rose during treatment to 11.3 +/- 0.2 g/dl. Three patients developed hypertension and in two their Cimino shunt closed. but there were no toxic side effects, organ damage, allergic reactions or antibodies against the hormone. The results show that the anaemia of patients on chronic dialysis can be treated effectively and without serious side effects with r-HEPO.

Adult↗
PubMed1988

Hormonal regulation of muscle protein catabolism in acutely uremic rats: effect of adrenalectomy and parathyroidectomy.

To examine the role of glucocorticoids and PTH on the enhanced protein catabolism of acute uremia, rats were rendered uremic and had their adrenals or their parathyroid glands concomitantly removed. Adrenalectomy resulted in a marked reduction of urea generation in uremic animals due to decrease of myofibrillar protein breakdown as indicated by lower serum levels of Nt-methylhistidine and a reduction in the activity of the myofibrillar proteinase from skeletal muscle. This reduced urea formation was accompanied by marked hypoglycemia. Parathyroidectomy, on the other hand, caused no change of those parameters of protein catabolism, suggesting that PTH does not account for the protein degradation observed in acutely uremic rats.

Acute Disease↗
PubMed1988

Evidence for the role of proteinases in uremic catabolism.

Enhanced muscle protein breakdown has been demonstrated in acutely uremic rats by numerous authors. In order to investigate the pathogenetic role of skeletal muscle proteinases leupeptin, a low-molecular weight proteinase inhibitor, was administered intraperitoneally to acutely uremic rats. Twenty-four hours after bilateral nephrectomy, leupeptin-treated animals displayed significantly lowered serum urea levels (-32%), as compared to untreated uremic rats. As a sign of muscle protein breakdown, plasma levels of Nt-methylhistidine, an indicator of myofibrillar protein degradation, were also decreased (-35%) in the uremic animals treated with leupeptin as compared to untreated uremic rats. Finally, leupeptin treatment resulted in a significant inhibition of the myofibrillar alkaline proteinase activity, a proteinase which has been related to various catabolic conditions. These findings suggest that the increased muscle protein breakdown in uremia is caused by enhanced activity of muscular proteinases and that anti-proteolytic agents display favourable effects on the enhanced protein degradation observed in acute uremia.

Acute Disease↗
PubMed1988

Eglin C fails to reduce catabolism in acutely uremic rats.

Increased release of proteinases from polymorphonuclear leukocytes, namely elastase, has been incriminated to take part in the pathogenesis of enhanced muscle protein breakdown in acute renal failure. In order to investigate, whether inhibition of the granulocyte proteinase elastase and cathepsin G would have a beneficial effect on the extent of muscle protein degradation, eglin C, a potent inhibitor of the granulocyte proteinase elastase and cathepsin G, was administered intraperitoneally to acutely uremic rats. 48 hours after bilateral nephrectomy, eglin C-treated animals displayed no significant difference, as far as serum levels of SUN, glucose and Nt-methylhistidine are concerned. Similarly, eglin C treatment failed to reduce the stimulated activity of the alkaline myofibrillar proteinase in comparison to binephrectomized controls. Hence, according to these results, granulocyte proteinases do not seem to be an important mediator of uremic catabolism, since their inhibition by eglin C does not reduce enhanced protein breakdown in acutely uremic rats.

Acute Disease↗
PubMed1988

Activation of leukocytes during prolonged physical exercise.

Previous studies have demonstrated an increment of circulating leukocytes and enhanced secretion of interleukin-1 by monocytes and macrophages during physical exercise. In the present study the effect of physical exertion on the activity of polymorphonuclear (PMN) leukocytes was investigated. Following both short-term (running 2,000 meters) and long-term (running 10,000 meters) exertion, phorbol-stimulated chemiluminescence, as an indicator of leukocytic oxygen radical formation and release of leukocytic elastase, as a parameter of degranulation, were determined immediately after running. The number of circulating leukocytes increased both after short-term (+21%) and long-term (+61%) exercise. There was a minor release of PMN elastase following short-term activity causing plasma levels of this compound to rise from 100 +/- 4.0 ng/ml to 116 +/- 12.3 ng/ml. Long-term exercise, on the other hand, induced a significant increase of elastase plasma levels from 107 +/- 9.1 ng/ml to 300 +/- 23.4 ng/ml, suggesting a remarkable release of this proteinase from neutrophils. Based on these findings we conclude that during physical exercise degranulation of PMN leukocytes occurs. Moreover, the fact that phorbol-stimulated chemiluminescence is decreased after running demonstrates an impaired capability of white cells to generate oxygen radicals.

Adult↗
PubMed1988

Blood rheology and hypertension in hemodialysis patients treated with erythropoietin.

Fifteen hemodialysis patients suffering from stable anemia were treated with recombinant human erythropoietin (r-HuEPO). Within 16 weeks, hematocrit values increased from 23.7 +/- 1.2 to 35.7 +/- 0.2%. Simultaneously, mean predialytic blood pressure rose significantly from 131/79 to 139/85 mm Hg. Three out of 15 patients developed frank hypertension and had to be put on antihypertensive therapy. When the hematocrit was lowered again from 36.3 +/- 1.8 to 30.5 +/- 1.2% in these 3 patients, blood pressure was attenuated and the antihypertensive medication could be reduced or abolished. With rising hematocrit values, whole blood viscosity increased at both low (+42%) and high shear rates (+33%) without reaching the values seen in healthy subjects. By contrast, plasma viscosity was already elevated in hemodialysis patients prior to r-HuEPO treatment and showed only a slight, but insignificant increase during r-HuEPO treatment. Since whole blood viscosity is one factor that determines vascular resistance, it is conceivable that the development of hypertension during correction of the renal anemia is, at least partly, due to an increment of blood viscosity.

Adult↗
PubMed1988

Reduction of urea generation and muscle protein degradation by adrenalectomy in acutely uremic rats.

The effect of adrenalectomy on the enhanced protein degradation in acute uremia was investigated. Therefore, serum urea nitrogen, urea N appearance and Nt-methylhistidine were followed in bilaterally nephrectomized rats. At 48 h after induction of uremia the animals displayed serum urea nitrogen levels of 223 +/- 9.5 mg/dl as compared to 26.0 +/- 1.0 mg/dl in sham-treated rats. This increment was significantly attenuated in acutely uremic, adrenalectomized animals (176 +/- 6.0 mg/dl). When these rats were substituted with corticosterone (5 mg/kg body weight), serum urea nitrogen readily increased to levels of acutely uremic animals with intact adrenal glands (225 +/- 6.0 mg/dl). The net generation of urea, as determined by the urea N appearance, was significantly increased during acute uremia (370 +/- 26 mg/48 h) as compared to SHAM animals (220 +/- 15 mg/48 h). This increment of urea formation could almost be completely reversed by simultaneous adrenalectomy (238 +/- 20 mg/48 h). When these rats were substituted with corticosterone, the urea N appearance rebounded to values quite comparable to acutely uremic rats with intact adrenal glands (363 +/- 30 mg/48 h). To determine whether skeletal muscle proteins might serve as a source for the enhanced protein degradation in acute uremia, plasma levels of Nt-methylhistidine were measured. Bilaterally nephrectomized rats had Nt-methylhistidine values of 9.6 +/- 1.0 micrograms/ml. In acutely uremic rats without adrenal glands, Nt-methylhistidine levels were found to be significantly decreased (6.0 +/- 0.4 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

Chronic ethanol ingestion enhances catabolism and muscle protease activity in acutely uremic rats.

Skeletal muscle wasting in men as well as enhanced urea production in animals due to ethanol consumption has been demonstrated by numerous authors. Furthermore, the outcome of acute renal failure is closely related to the extent of catabolism. The present study was performed to investigate whether chronic ethanol exposition prior to binephrectomy (BN) may represent a predisposing factor for enhanced protein breakdown. Rats underwent BN after exposure to ethanol or isocaloric substrate for 4 weeks. Blood chemistries and muscle samples were obtained 48 h after BN. Animals fed with ethanol revealed significantly higher levels of serum urea nitrogen (SUN) and urea nitrogen appearance (UNA) in comparison to controls. Preconditioning on ethanol-derived calories induced an accelerated fractional degradation rate of myofibrillar protein as demonstrated by a significantly enhanced serum Nt-methylhistidine/creatinine ratio. The increase in serum indicators of enhanced myofibrillar breakdown correlated with the stimulated activities of alkaline myofibrillar protease and cathepsin B. Finally, serum corticosterone levels were enhanced in the experimental group in comparison to controls, indicating an ethanol-related adrenocortical stimulation to be a possible mediating factor of enhanced catabolism in ARF. Thus, chronic ethanol intake prior to the onset of ARF seems to be a risk factor for enhanced catabolism in the course of acute uremia.

Acute Kidney Injury↗