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Biomedical subjects

M Teschner

Publications and source records attributed to M Teschner.

At least 73 records · Page 4Linked to original sources
PubMed1992

Effect of renal disease on glomerular proteinases.

Until now, little is known about the self-perpetuating mechanism leading to terminal renal failure in chronic renal disease. The common pathological feature of progressive renal insufficiency is focal and segmental glomerulosclerosis. The experimental counterpart of this process is represented by models of streptozotocin diabetes, Adriamycin nephropathy and Goldblatt hypertension. The main initiating hallmark of glomerulosclerosis is an accumulation of glomerular proteins, whose balance is apparently influenced by the activity of glomerular proteinases. In isolated glomeruli of kidneys from experimental animals, total proteinase activity was assayed with an unspecific but sensitive azocasein assay. The activity was significantly reduced in all experimental models at acid and neutral pH when relating enzyme activity to the glomerular protein and DNA content. The demonstration of reduced glomerular proteinase activity in the animal models of glomerulosclerosis could represent a new additional common pathogenetic mechanism. Glomerular protein accumulation could be a result of a synergistic interaction between hemodynamic and biochemical factors; we suggest the latter to be a decrease in glomerular proteinase activity.

Animals↗
PubMed1992

Role of glomerular proteinases in the evolution of glomerulosclerosis.

Recent studies suggest that proteolytic enzymes located within the glomerulus are involved in the degradation of extracellular matrix components. In the present investigation glomerular proteinase activities were followed in a variety of non-immune-mediated renal diseases as well as during different dietary manipulations. Azocaseinolysis was significantly reduced in the obese Zucker rat compared with lean littermates (pH 5.4:8.9 +/- 0.4 vs 11.4 +/- 0.7; pH 7.4:5.8 +/- 0.7 vs 9.3 +/- 0.6 arb. U/mg protein). When the glomerular proteolytic capacity was measured in old rats, again a significant decline in proteolysis was observed (pH 5.4:9.8 +/- 0.8 vs 17.7 +/- 0.8; pH 7.4:6.4 +/- 0.7 vs 11.7 +/- 0.5 arb. U/mg protein). In Goldblatt hypertensive rats the unclipped kidney, which is exposed to high blood pressure, revealed lower glomerular azocaseinolytic activity compared with the contralateral clipped kidney (pH 5.4:8.1 +/- 0.4 vs 12.9 +/- 0.5 arb. U/mg protein). In parallel, the cathepsin B content was also diminished in glomeruli from kidneys exposed to hypertension. When proteinases were followed in glomeruli from intact kidneys of rats fed protein-modified diets (fraction of casein 0.05, 0.20 or 0.60) a significant fall in the activities of cysteine proteinases, e.g. cathepsin B (casein 0.05:1,498 +/- 110 vs casein 0.60:914 +/- 84 microU/micrograms DNA), as well as metalloproteinases, e.g. collagenase (casein 0.05:233 +/- 14 vs casein 0.60:137 +/- 11 microU/micrograms DNA), occurred. These data indicate that in both early and late stages of glomerulosclerosis, proteolytic activities within the glomerulus tend to be reduced, which could allow extracellular matrix accumulation. Moreover, changes in dietary protein intake resulted in profound alterations of glomerular proteinases.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Intraglomerular fibronectin accumulation and degradation in obese Zucker rats.

The obese Zucker rat is a classic model of non-immune mediated spontaneous focal glomerulosclerosis. An important initiating hallmark of glomerulosclerosis in this model is mesangial matrix expansion. Fibronectin, a highly biologically active glycoprotein, is a normal constituent of mesangial extracellular matrix. Using a quantitative method based on enzyme immunoassay we assessed the intraglomerular fibronectin content and its degradation in obese Zucker rats and their lean littermates. In the obese Zucker rats the glomerular fibronectin content was significantly higher in comparison to the controls (88 +/- 6 vs 48 +/- 4 ng/10(3) glomeruli). Furthermore, proteinase activity against fibronectin was significantly reduced in the glomeruli of obese Zucker rats when compared to control animals (at pH 5.4: 186 +/- 6 U/mg protein vs 286 +/- 14 U/mg protein, at pH 7.4: 152 +/- 12 U/mg protein vs 193 +/- 12 U/mg protein). These data demonstrate that in obese Zucker rats there is a glomerular accumulation of fibronectin which we propose is at least partly due to diminished proteolytic digestion. Whether accumulation of intraglomerular fibronectin contributes to progressive glomerulosclerosis remains a matter of debate.

Animals↗
PubMed1991

Obese Zucker rat: potential role of intraglomerular proteolytic enzymes in the development of glomerulosclerosis.

The obese Zucker rat is a classic model of non-immune-mediated spontaneous focal glomerulosclerosis. An early morphological hallmark of glomerular damage in the obese Zucker rat is a mesangial expansion, which precedes and mediates the development of glomerular damage in these animals. This study was designed to investigate whether there might be a reduced activity of glomerular proteinases in kidneys of obese Zucker rats, thereby being involved in the pathogenesis of mesangial expansion, which is mainly due to protein overloading. In fact, we found a decreased proteinase activity in ultrasonically destroyed isolated glomeruli obtained by a differential sieving technique in obese Zucker rats compared with their lean littermates. This held true at acid as well as at neutral pH and could be confirmed when proteinase activity was related to DNA instead of protein. When investigating the glomerular cathepsin B content--this is a lysosomal enzyme with acid pH optimum, which is involved in the degradation of glomerular structural as well as filtered plasma proteins--we found a significantly increased level in the kidneys of obese Zucker rats. Hence, the intraglomerular proteinase activity is reduced in the face of enhanced glomerular content of at least lysosomal proteinases. The underlying reason for this depressed activity remains to be established. We propose that reduced activities of intraglomerular proteinases may be important in the pathogenesis of mesangial matrix expansion in obese Zucker rats, an important initiating hallmark of glomerulosclerosis in this model.

Animals↗
PubMed1991

Proteinase activity in isolated glomeruli of Goldblatt hypertensive rats.

In Goldblatt rats, the kidney exposed to high blood pressure reveals glomerulosclerosis. Moreover, in preexisting parenchymal renal disease, the development of glomerulosclerosis is accelerated in the unclipped kidney. Up to now, the pathogenetic mechanism underlying the development of glomerulosclerosis due to systemic hypertension has not completely been resolved. Traditionally, hemodynamic mechanisms have been discussed. This study was performed to investigate whether there might be a decreased activity of glomerular proteinases in the unclipped kidney of Goldblatt rats as a potential pathogenetic factor for glomerulosclerosis. 20 weeks after the surgical intervention, we found a reduced proteinase activity in ultrasonically destroyed isolated glomeruli obtained by differential sieving technique in comparison with the contralateral clipped kidney and the kidneys of sham-operated normotensive controls. This could be confirmed, when proteinase activity was related to DNA instead of protein. When investigating glomerular cathepsin B-content, a lysosomal enzyme, which is able to degrade glomerular structural as well as non-structural proteins, we found a decreased level in the kidney of Goldblatt rats exposed to systemic hypertension in comparison with normotensive control animals. Basing on these results we presume that glomerular protein accumulation and concomitant glomerulosclerosis due to systemic hypertension might be a result of a synergistical interaction between hemodynamic factors and biochemical ones; we suggest one of the latter to be a decreased glomerular proteinase activity.

Animals↗
PubMed1991

[Changes in renal function in heart failure and their modification by conversion enzyme inhibitors].

In congestive heart failure renal hemodynamics are characterized by a decrease of fractional renal blood flow (renal fraction of the cardiac output) and marked changes of the intrarenal circulation. The latter consists of cortical hypocirculation and an enhanced medullary blood flow in the presence of a relative rise in glomerular filtration rate (GFR). This compensatory increment of GFR is mediated by a stimulation of prostaglandins (dilatation of vas afferens) as well as the renin-angiotensin- and adrenergic systems (contraction of vas efferens). Therapy with ACE inhibitors influences renal function in a complex manner. A decline in GFR resulting in the worst case in acute renal failure (ARF) may be caused by two pathogenetic possibilities: 1. critical reduction in renal perfusion pressure (below 70 mm Hg) and/or 2. loss of the autoregulation of GFR by relaxation of the constricted vas efferens induced by stimulation of the renin-angiotensin-systems (RAS). Activation of the RAS might be a consequence of severe renal hypocirculation as well as a diuretic induced volume and sodium depletion (contraction of the effective arterial blood volume). On the other hand, ACE inhibitors may improve renal blood flow and glomerular filtration rate. This may be due to a rise in cardiac output, dilatation of vas efferens and occasionally vas afferens and an increase of the ultrafiltration coefficient. The deterioration of renal function caused by ACE-inhibitors may be prevented by avoiding a volume and sodium deficit (withdrawal or reduction of diuretics) and careful titration of the ACE-inhibitor starting with lowest dosages.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Serum phospholipase A and prognosis in intensive care patients.

The clinical value of phospholipase measurements in serum is as yet an open question, particularly with respect to the prognosis quoad vitam. Sensitivities and specificities at different decision levels for unselected intensive care patients are reported and discussed.

Adolescent↗
PubMed1989

[Progression of chronic renal failure. Pathogenesis and therapeutic aspects].

Once established, chronic renal failure does not progress only when the specific triggering metabolic, immunological or vascular-renal underlying disease persists. Unspecific factors also cause progression of chronic renal failure when the underlying renal disease is no longer active or has been successfully treated. Today, such unspecific progression factors are considered to be glomerular capillary hyperfiltration/hyperperfusion, the effects of angiotensin II, uremic-associated lipid metabolic disorder, hyperphosphatemia or secondary hyperparathyroidism, as also the effect of glucocorticoids. For therapy, apart from adequate antihypertensive management, a low-protein diet and treatment of the lipid metabolic disorder and the secondary hyperphosphatemia, is recommended in the patient with chronic renal disease.

Animals↗
PubMed1989

Independence of enhanced protein catabolism from glucocorticoids in chronically uremic rats.

Patients with chronic renal failure are prone to develop negative nitrogen balance resulting clinically in wasting and malnutrition. To study the role of glucocorticoids in the pathogenesis of uremic catabolism, we determined urinary excretion rates of urea and Nt-methylhistidine in chronically uremic rats with and without RU 38486, a potent antiglucocorticoid. In comparison to pair-fed non-uremic animals, chronically uremic rats displayed significantly enhanced ureagenesis, as demonstrated by increased urinary urea excretion, and myofibrillar protein breakdown, as indicated by increased excretion rates of urinary Nt-methylhistidine. The administration of RU 38486 to chronically uremic rats, however, did not result in a normalization of urinary excretion of Nt-methylhistidine. Similarly, the antiglucocorticoid did not influence the extent of ureagenesis in our uremic animals, as it was demonstrated by comparable levels of urinary urea excretion. This suggests that glucocorticoids are not involved in the pathogenesis of enhanced catabolism in chronic renal insufficiency.

Animals↗
PubMed1989

Effect of parathyroid hormone on elastase release from human polymorphonuclear leucocytes.

Acute and chronic renal failure are clinical states associated with secondary hyperparathyroidism and increased catabolism. It has been suggested that elevated proteolytic activity is present in the blood in these clinical states. It is, theoretically, possible that the excess blood levels of parathyroid hormone (PTH) in patients with these disorders stimulate release of proteases, since this latter process is calcium dependent and PTH enhances entry of calcium into cells. The present study examined the effect of PTH and its amino- and carboxyterminal fragments on elastase release from polymorphonuclear leucocytes (PMNL), and evaluated the mechanisms underlying such an action. 1-84 PTH stimulated elastase release from PMNL in a dose-dependent and time-dependent manner. This effect of the hormone was abolished by its inactivation as well as by the presence of EDTA. Verapamil, trifluoperazine and W-7 reduced but did not abolish the 1-84 PTH-induced stimulation of elastase release from PMNL. Phorbol ester (PMA) also stimulated elastase release but both PTH or PMA-induced elastase release was blunted by staurosporin, an inhibitor of protein kinase C. The 19-84 carboxyterminal PTH also produced significant stimulation of elastase release from PMNL but the amino-terminal 1-34 PTH or other peptide hormones (insulin, calcitonin, and ACTH) had no stimulatory effect on elastase release.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1989

Decreased proteinase activity in isolated glomeruli of streptozotocin diabetic rats.

The important initiating process of diabetic nephropathy is the glomerular accumulation of proteins which has been proposed to be due to a synergistic interaction of the disturbed intrarenal hemodynamic and the altered chemical composition of glomerular components. This study was performed to investigate whether there might be a reduced activity of glomerular proteinases in streptozotocin diabetic rats. Three weeks after the induction of diabetes by means of streptozotocin, we found a decreased proteinase activity in ultrasonically destroyed isolated glomeruli obtained by a differential sieving technique in comparison to nondiabetic controls. This held true at acidic (16.59 +/- 1.56 vs. 22.19 +/- 1.94 U/min/mg protein) as well as at neutral pH (7.82 +/- 0.55 vs. 10.67 +/- 0.81 U/min/mg protein) and could be confirmed when proteinase activity was related to the single glomerulus or DNA instead of protein. Treatment with insulin was effective in improving the degradative capacity at both pH levels. We suggest that decreased proteinase activity in diabetic glomeruli may, at least partly, explain the glomerular protein accumulation in diabetic nephropathy.

Animals↗
PubMed1989

Hypercatabolism in acute renal failure--mechanisms and therapeutical approaches.

Despite intensive efforts in the nutritional treatment of hypercatabolic acute renal failure (ARF), its prognosis is still deleterious. The most important factor determining the outcome of ARF is the extent of catabolism which is caused by alterations of the hormonal milieu, enhanced proteolytic activity, the hemodialysis process and the patient's underlying or superimposed illness like surgical or nonsurgical trauma, rhabdomyolysis and septicemia. Up to now, in randomly assigned studies, hyperalimentation with protein- and nonprotein-derived calories has failed significantly to improve the nutritional status of the patient, although maximal doses of amino acids have been administered. Since there is some evidence from animal experiments that high doses of amino acids might act nephrotoxic, perhaps rather than further increasing the quantity of amino acids, in the future antiproteolytically acting substances may help in the management of hypercatabolic ARF. Possibly the use of amino acid solutions, enriched with branched chain amino acids, might represent a new approach in the management of negative nitrogen balance in ARF.

Acute Kidney Injury↗
PubMed1989

Catabolic effects of ethanol in chronically uremic rats.

Both ethanol consumption and uremia are considered to be associated with wasting, malnutrition and debilitation. The present study was designed to investigate as to whether ethanol exerts a stimulatory effect on the catabolic state of renal failure. Rats underwent 5/6-nephrectomy and were fed either with or without ethanol. The degree of uremia was comparable in both groups. Ethanol-fed uremic rats, however, displayed higher serum levels of urea (+ 103%) and glucose (+29%), as compared to uremic animals without alcohol. Subsequently, the urea N appearance was enhanced (+60%) in uremic rats with alcohol as compared to uremic animals without alcohol. In sham rats urea N appearance was also increased (+39%) following ethanol administration in comparison to sham-operated rats without alcohol, albeit to a lesser degree. Urinary Nt-methylhistidine excretion, an indicator of myofibrillar protein breakdown, was enhanced throughout the experiment in uremic rats receiving ethanol. Finally, ethanol caused higher urinary excretion rates of corticosterone in uremic animals as compared to uremic rats without ethanol. There was a significant correlation between urinary corticosterone excretion and both urea N appearance and urinary Nt-methylhistidine excretion. We conclude that ethanol consumption further aggravates the catabolic state of uremia and that this is mediated by an increment in glucocorticoid production.

Alcohol Drinking↗
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

Biodegradation of crude oils.

Petroleum from well sites in the Gifhorn Trough (Lower Saxony, NW-Germany) and the Maracaibo Basin (Venezuela) contained various types of microorganisms capable of degrading crude oils. Genetically related oils were inoculated with the isolated microorganisms and the degradation of the oils was followed by chromatographic techniques. Parameters important for the reactions (pH, supply of oxygen, nitrogen and phosphorus, reaction medium) were monitored and optimized. The degradation of n-alkanes was followed closely. Microorganisms active in degradation (yeast, bacteria) easily survived a period of inactivity due to missing nutrients and were reactivated within hours to degrade newly added crude oil. Under substrate-limiting conditions selectivity of degradation was found, destroying medium-chain n-alkanes (C20, C21) at a faster rate than long-chain n-alkanes (C30, C31). During degradation the physical parameters of the crude oils (e.g. density, viscosity, average molecular weight) were altered and shifted into the direction of heavy oil. In vitro degraded oil is very similar to oil degraded in nature. Aromatic hydrocarbons and biomarker molecules (steranes and triterpanes) were not degraded under the conditions used. Pyrolysis-GC analysis of asphaltenes revealed no significant changes in the composition of pyrolyzates during biodegradation. There is sufficient evidence that heavy oils - besides some other effects - are generated by the in situ-biodegradation of conventional oils.

Alkanes↗