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M Teschner

Publications and source records attributed to M Teschner.

At least 91 records · Page 5Linked to original sources
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

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↗
PubMed1988

Reduction of muscle protein degradation by leupeptin in acutely uremic rats.

Enhanced muscle protein breakdown has been demonstrated in acutely uremic rats by numerous authors. These findings have been used to explain the clinical signs of muscle wasting and enhanced urea-N appearance, frequently observed in patients suffering from uremia. In order to investigate whether inhibition of skeletal muscle proteinases would have a favourable effect on the extent of muscle protein degradation, leupeptin, a low-molecular-weight proteinase inhibitor, was administered intraperitoneally to acutely uremic rats. 24 h after bilateral nephrectomy, leupeptin-treated animals displayed significantly lowered serum urea levels (-32%), and hence decreased urea-N appearances (-39%) 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 antiproteolytic agents display favourable effects on the enhanced protein degradation observed in acute uremia.

Acute Disease↗
PubMed1988

Effects of acetate during regular hemodialysis.

The utilization of acetate and its effects on acid-base balance and on free fatty acid metabolism were investigated during regular hemodialysis (HD). Fourteen patients with chronic renal failure were studied during two successive dialysis treatments for which either acetate or bicarbonate were used as a buffer anion in the dialysate. In the acetate studies the mean plasma acetate concentration in the arterial line rose from 0.16 mM to 4.67 mM, while it rose from 0.17 mM to 0.62 mM during bicarbonate dialysis. There was a linear relationship between acetate utilization and the acetate concentration in the venous line. The increase of the blood pH during bicarbonate HD was due to an immediate increase of HCO3, whereas acetate caused a smaller HCO3 rise and a pronounced fall of the pCO2. The heart rate was higher during acetate than during bicarbonate HD. During both types of dialysis there was a twofold rise of total FFA as well as the individual fatty acids palmitate, palmitoleate, oleate, stearate and linoleate which was of similar magnitude when acetate or bicarbonate were used. The postulated antilipolytic effect of the short-chain fatty acid acetate could not be demonstrated under the circumstances of routine hemodialysis. Pre-dialysis dopamine was elevated in 7 of the 11 patients and remained high during both types of HD; other hormones were normal during acetate and bicarbonate HD.

Acetates↗
PubMed1987

Evidence for reduced catabolism by the antiglucocorticoid RU 38486 in acutely uremic rats.

Previous studies suggested that increased blood levels of, or increased tissue sensitivity to, glucocorticoids may contribute to catabolism in acute uremia. To examine this possibility we determined urea nitrogen (urea-N) appearance, plasma levels of Nt-methylhistidine and the activity of the alkaline myofibrillar proteinase in acutely uremic rats with and without treatment with RU 38486, a selective antiglucocorticoid. Forty-eight hours after bilateral nephrectomy, the rats had markedly elevated serum levels of urea-N, creatinine, potassium and phosphorus. In uremic rats receiving RU 38486, comparable levels of serum creatinine were found, but the serum levels of urea-N (221 +/- 4 vs. 259 +/- 5 mg/dl) and phosphorus (6.5 +/- 0.3 vs. 8.5 +/- 0.4 mmol/l) 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 h after bilateral nephrectomy. 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 microgram/dl, whereas the administration of RU 38486 caused a significant decline in the levels of this amino acid (7.6 +/- 0.5 microgram/dl). This reduction in Nt-methylhistidine was associated with a concomitant decrease of myofibrillar proteinase activity in muscle tissue homogenates. Compared to sham-operated animals, this proteinase activity was increased by 30% in uremic rats, but was normal in those given RU 38486. Taken together, these data support the view that in acute uremia accelerated ureagenesis occurs, while enhanced muscle protein breakdown, owing to an increment in myofibrillar proteinase activity, provides the necessary amino acid precursors.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1987

Stimulation and inhibition of elastase release from human neutrophil-dependence on the calcium messenger system.

The neutral proteinase elastase is released from polymorphonuclear (PMN) leukocytes in various physiological and pathological conditions. Aim of the present study was to gain further insight into the mechanisms which govern the liberation of this proteinase. Therefore, the effects of the calcium ionophore A23187 and of the protein kinase C activator phorbol myristate acetate (PMA) on neutrophils were investigated in human whole-blood samples. Furthermore, the inhibitory effects of the calcium channel blocker verapamil and of the calmodulin blocker trifluoperazine were followed. A23187 induced a release of elastase from neutrophils in a dose- and time-dependent manner. Complexation of extracellular calcium by ethylenediamine tetraacetate (EDTA) completely abolished the stimulatory effect of A23187. In a concentration of 10(-4) M verapamil was capable of attenuating (-49%) the A23187-induced secretion of PMN elastase. Besides the increase in intracellular calcium concentration, the activation of protein kinase C by PMA did also cause a release of neutrophil elastase. This release was strictly depending on the concentration of PMA and the time of incubation. In contrast to the stimulatory effect of A23187, the PMA-induced liberation of neutrophil elastase was attenuated, but not completely abolished, by complexation of extracellular calcium with EDTA. Both 10(-4) M verapamil (-43%) and 10(-5) M trifluoperazine (-42%) were able to reduce the PMA-induced release of neutrophil elastase. Based upon these data, we conclude that both the translocation of calcium intracellularly by A23187 and the activation of protein kinase C by PMA stimulate the release of neutrophil elastase. Verapamil and trifluoperazine were capable of suppressing the stimulation of elastase release.

Adult↗
PubMed1987

Stimulation and inhibition of elastase release from human neutrophils dependent on the calcium messenger system.

The neutral proteinase elastase is released from polymorphonuclear (PMN) leukocytes in various physiological and pathological conditions. Aim of the present study was to gain further insight into the mechanisms which govern the liberation of this proteinase. Therefore, the effects of the calcium ionophore A23187 and of the protein kinase-C activator phorbol myristate acetate (PMA) on neutrophils were investigated in human whole-blood samples. Furthermore, the inhibitory effects of the calcium channel blocker verapamil and of the calmodulin blocker trifluoperazine were followed. A23187 induced a release of elastase from neutrophils in a dose- and time-dependent manner. Complexation of extracellular calcium by ethylenediamine tetraacetate (EDTA) completely abolished the stimulatory effect of A23187. In a concentration of 10(-4) M verapamil was capable to attenuate (-49%) the A23187-induced secretion of PMN elastase. Beside the increase in intracellular calcium concentration, the activation of protein kinase C by PMA did also cause a release of neutrophil elastase. This release was strictly depending on the concentration of PMA and the time of incubation. In contrast to the stimulatory effect of A23187, the PMA-induced liberation of neutrophil elastase was attenuated, but not completely abolished, by complexation of extracellular calcium with EDTA. Both 10(-4) M verapamil (-43%) and 10(-5) M trifluoperazine (-42%) were able to reduce the PMA-induced release of neutrophil elastase. Based upon these data, we conclude that both the translocation of calcium intracellularly by A23187 and the activation of protein kinase C by PMA stimulate the release of neutrophil elastase. Verapamil and trifluoperazine were capable to suppress the stimulation of elastase release.

Adult↗
PubMed1985

Role of alcohol in clinical nephrology.

Different nephrological derangements are observed in severe alcoholics. Until now the direct toxicity of ethanol is only shown in the fetal alcohol syndrome with various malformations of the genitourinary tract. In the adult the kidney is often involved in the development, maintenance and counterregulation of complex electrolyte disturbances like phosphate and potassium hypoglycemia etc. The alcohol associated retention of urate, induced by hyperlactatemia and/or increased beta-hydroxybutyrate concentration is only rarely complicated by urate nephropathy. Alcohol intoxication (acute and chronic) predisposes to rhabdomyolysis with the risk of acute renal failure. There are some hints that chronic alcoholism with myopathy increases the vulnerability of the kidney for further toxic agents. In rats glycerol induced renal failure is enhanced by alcohol pretreatment. Finally, regular alcohol consumption raises the blood pressure, which per se is a risk factor for renal damage.

Acute Kidney Injury↗
PubMed1985

Nutrition in acute renal failure.

An important prognostic factor of acute renal failure (ARF) is the nutritional status of the patient. Malnutrition in ARF is mainly a consequence of profound catabolism, caused by alterations of the hormonal milieu, physical inactivity, infection, an enhanced proteolytic activity and the hemodialysis process. In the management of these patients, optimal nutritional intake must especially be discussed under the aspect of reducing catabolism. In catabolic ARF, an energy intake of about 50 kcal/kg/day provided by hypertonic glucose, may be adequate. The requirement of essential and nonessential amino acid solutions in respect of their composition and quantity is not clearly defined. High doses of amino acids failed to improve negative nitrogen balance in catabolic ARF. Recent approaches in order to reduce net protein breakdown imply new combinations of amino acid formulations or pharmacological trials for instance with antiproteolytic substances.

Acute Kidney Injury↗
PubMed1976

Appearance of IgG (Fc) receptor(s) on cultured human fibroblasts infected with human cytomegalovirus.

Cultured human diploid fibroblasts (WI-38) after infection with human cytomegalovirus (CMV) but not when uninfected, could hemadsorb sheep red blood cells (SRBC) coated with rabbit anti-SRBC IgG. The adsorption of IgG-coated SRBC to virus-infected cells was completely abolished if the tests were carried out in the simultaneous presence of rabbit antiserum elicited against CMV. Normal sera of rabbit or human origin as well as purified human IgG but not Fab fragment of human IgG could also abolish the binding of sensitized SRBC to CMV-infected fibroblasts. Active metabolism on the part of CMV-infected fibroblasts proved to be an important requisite for demonstrating binding of sensitized SRBC to their surfaces. By using an indicator Staphylococcus aureus to which rabbit antiserum against normal human IgG, IgM, or IgA was bound via Fc fragments, evidence has been obtained which suggests the existence of receptor(s) on CMV-infected WI-38 cells that react specifically with Fc region of human IgG.

Animals↗
PubMed1974

In vitro antilisterial activity of soluble product(s) released from Listeria-immune murine peritoneal macrophages.

The importance of macrophages as effector cells in cellular reactions of immunity and hypersensitivity is well established (8). Macrophages activated as a result of specific immunological events exhibit increased microbicidal activity not only for the primary organism used for immunization purposes but also against unrelated intracellular pathogens (7). It is believed that the acquisition of this bactericidal or bacteriostatic activity is conferred on macrophages by materials released during the interaction of specifically immune lymphocytes with the antigen (Fowles et al., 1973; Godal et al., 1971; Jones and Youmans, 1973; Krahenbuhl and Remington, 1971; Mackaness, 1971; Patterson and Youmans, 1970). The antimicrobial activity in these studies refers to the intracellular inhibition and/or killing of the organisms; no attempts were made to assess the effect of activated macrophages on the extracellularly residing organisms. In an earlier study with the pathogenic yeastlike fungus Cryptococcus neoformans, we observed that freshly collected peritoneal macrophages from mice pretreated with a variety of nonspecific agents or from specifically immune mice possessed the capacity to exert anti-cryptococcal effect both on intracellular yeasts as well as those present in the extracellular milieu (Sethi et al., 1971; Sethi and Pelster, in press). Our results suggest that soluble product(s) released from mouse macrophages immune to Listeria monocytogenes can exert antilisterial activity under in vitro conditions.

Animals↗