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Biomedical subjects

W Pfaller

Publications and source records attributed to W Pfaller.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effects of chronic hyperfiltration on proximal tubule bicarbonate transport and cell electrolytes.

The compensatory response to unilateral nephrectomy (UNX) was investigated by a combination of renal clearance, microperfusion, electron microprobe, and morphological techniques. Filtration rate was significantly elevated 21 days following UNX and associated with a marked stimulation of bicarbonate and fluid absorption in the proximal tubule. Analysis of kinetic data of bicarbonate transport demonstrated strong flow-dependent activation of bicarbonate absorption in both control and experimental condition. The bicarbonate level at which half-saturation (apparent Kd) of transport occurred decreased uniformly at higher flow rates, but maximal transport rates (apparent Vmax) in the proximal tubule doubled in the remnant kidney. The flow dependence of bicarbonate transport in control and experimental conditions can be explained by an apparent unstirred layer effect modifying radial bicarbonate gradients in the tubule. Both Na/H-exchange and electrogenic H secretion contribute to bicarbonate absorption, but only Na/H-exchange increased significantly in proximal tubules of UNX rats. Cell ion concentrations after UNX were unchanged in cortical tubules, consistent with proportionately enhanced apical and basolateral ion transport. Proximal tubule cell rubidium concentration measured after a 30-second rubidium infusion as an index of basolateral Na,K-ATPase activity was unchanged in UNX rats. Inasmuch as cell volume increased significantly (25%), these data are consistent with a proportionate and similar stimulation of rubidium uptake and Na,K-ATPase activity.

Animals↗
PubMed1995

In vitro nephrotoxicity of Russell's viper venom.

To assess direct nephrotoxicity of Russell's viper venom (RVV; Daboia russelii siamensis), isolated rat kidneys were perfused in single pass for 120 min. Ten micrograms/ml and 100 micrograms/ml RVV were administered 60 minutes and 80 minutes, respectively, after starting the perfusion. Furthermore, cultured mesangial cells and renal epithelial LLC-PK1 and MDCK cells were exposed to RVV (100 to 1000 micrograms/ml) for 5 minutes up to 48 hours. The IPRK dose-dependently exhibited reductions of renal perfusate flow (RPF, 7.7 +/- 2.4 vs. 16.5 +/- 0.7 ml/min g kidney wt in controls, experimental values given are those determined 10 minutes after termination of 100 micrograms/ml RVV admixture), glomerular filtration rate (GFR 141 +/- 23 vs. 626 +/- 72 microliters/min g kidney wt) and absolute reabsorption of sodium (TNa 8 +/- 1.7 vs. 79 +/- 9 mumol/min g kidney wt), and an increased fractional excretion of sodium (FENa 60 +/- 7 vs. 8 +/- 0.8%) and water (FEH2O 68 +/- 3.2 vs. 13 +/- 1.2%). Urinary flow rate (UFR) showed both oliguric and polyuric phases. Functional alterations of this type are consistent with ARF. Light and electron microscopy of perfusion fixed IPRK revealed an extensive destruction of the glomerular filter and lysis of vascular walls. Various degrees of epithelial injury occurred in all tubular segments. In cell culture studies RVV induced a complete disintegration of confluent mesangial cell layers, beginning at concentrations of 200 micrograms/ml. In epithelial LLC-PK1 and MDCK cell cultures only extremely high doses of RVV (> 600 and 800 micrograms/ml, respectively) led to microscopically discernible damage. These results clearly demonstrate a direct dose dependent toxic effect of RVV on the IPRK, directed primarily against glomerular and vascular structures, and on cultured mesangial cells.

Animals↗
PubMed1995

Ultrapure polymerized bovine hemoglobin (UPPBHb) improves integrity of the isolated perfused rat kidney (IPRK): effects on function and structure.

To test the oxyphoretic properties and potential nephrotoxic side-effects of polymerized hemoglobin solutions, isolated rat kidneys were perfused in a recirculating system for 180 min. Group I was perfused with a substrate enriched Ringer solution containing hydroxyethylstarch (HES) to produce isoncotic conditions. In group II HES was substituted in part by UPPBHb (34 g/l) with a high portion of low molecular weight molecules (= UPPBHb1). In group III 34 g/l of UPPBHb containing an increased fraction of high molecular weight polymers (= UPPBHb2) was used. Only UPPBHb2-perfused kidneys showed a reduced renal perfusate flow (RPF, 13.3 +/- 1.1 ml/min g kw), when compared to HES-perfused controls (15.5 +/- 0.8) and UPPBHb1 (15.1 +/- 1.2). Glomerular filtration rate (GFR) was significantly higher in UPPBHb1-perfused kidneys (902 +/- 107 vs 633 +/- 55 microliters/min g kw for HES). This difference became even more pronounced in the third hour of perfusion (474 +/- 125 vs. 103 +/- 33). In contrast, UPPBHb2 produced low initial GFR levels of 385 +/- 25, which had only a minor tendency to decline with time. Parallel to GFR, absolute reabsorption of sodium (TNa) andoxygen consumption (QO2) showed values of 110 +/- 16 and 5.46 +/- 0.33 mumol/min g kw in UPPBHb1-kidneys vs 83 +/- 6 and 5.09 +/- 0.27 in controls and vs 53 +/- 4 and 3.66 +/- 0.12 in UPPBHb2-kidneys. Fractional excretion of sodium (FENa), of potassium (FEK), and of water (FEH2O) in UPPBHb1 and UPPBHb2-perfused kidneys were not significantly different from HES-perfused controls at any time of perfusion. Urinary flow rate (UFR) was similar in UPPBHb1- and HES-kidneys. Nevertheless, control kidneys tended to render oliguric during the third hour of perfusion (UFR 19.9 +/- 4.1 microliters/min g kw), whereas UPPBHb1 preserved urinary flow in a better way (83.7 +/- 32.4). UFR of UPPBHb2-kidneys was significantly reduced initially (30.2 +/- 5.1 vs. 105 +/- 33 for HES), but increased steadily up to 67 +/- 23. In the UPPBHb1 and HES group, all functional parameters determined declined dramatically within the third hour of perfusion, whereas UPPBHb2 produced functional stability. The in vivo reaction pattern of renal autoregulation was better preserved in UPPBHb-perfused kidneys than in HES-perfused controls: 74 +/- 6 vs. 59 +/- 5 vs. 42 +/- 4% (of full autoregulatory response) for UPPBHb1, UPPBHb2, and HES kidneys, respectively. Light- and electron microscopic analysis revealed major alterations only for the outer medulla of HES-kidneys.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Clinical value of fructose 1,6 bisphosphatase in monitoring renal proximal tubular injury.

The usefulness of the gluconeogenic key enzyme fructose 1,6 bisphosphatase (FBPase), which is localized exclusively in the proximal nephron segment, as a marker compound to monitor injury of the proximal nephron segment during nephrotoxic therapy, was tested in a collective model of male patients treated for testicular cancer. These patients with normal kidney function were submitted to therapy with the nephrotoxic chemotherapeutics carboplatinum and a combination of cisplatinum, etoposide, bleomycin and ifosfamide. The release of FBPase activities into the urine was monitored during the initial two treatments over a period of eight days. The urinary enzyme activities measured were compared to the excretion of the "proximal tubular injury markers" N-acetyl-beta-D-glucosaminidase (NAG) and alpha 1-microglobulin (alpha 1m). The presence of glomerular damage was determined by measurement of urinary excretion rates of albumin (ALB) and IgG. In addition, protein excretion patterns following chemotherapy were monitored. The combined administration of cisplatin, etoposide and ifosfamide resulted in a pronounced proximal tubular injury as shown by the release of FBPase into the urine. This is substantiated by simultaneously increased excretion rates for NAG and alpha 1m. Proximal tubular toxicity was found to be less severe when cisplatin was combined with etoposide and bleomycin and was nearly absent following carboplatinum monotherapy. Carboplatinum only affected glomerular function and resulted in an elevated ALB and IgG excretion. From this model investigation it can be delineated that determination of urinary FBPase activities ensures a sensitive and reliable identification of proximal nephron damage.

Acetylglucosaminidase↗
PubMed1993

Structural reaction pattern of hepatocytes following exposure to hypotonicity.

Isolated rat hepatocytes were exposed to hypotonic media (225 mosmol/l) for 5 and 15 min and processed for a quantitative electron microscopic stereologic analysis. Within 5 min of hypotonicity, the hepatocyte volume increased by 25% and thereafter displayed a volume regulatory decrease leading to mean cellular volume, which was 16% above that of controls. Stereologic analysis of the major subcellular compartment, the cytosol, showed an identical change as the whole cell. In contrast to that, the mitochondrial compartment increased in volume by 30% within the first 5 min of exposure and returned by regulatory volume decrease back to values of the isotonic controls after 15 min of hypotonicity. In contrast, hypotonicity (220 mosmol/l)-induced stimulation of flux through mitochondrial glutaminase and the glycine cleavage enzyme complex, as assessed by 14CO2 production from [1-14C]glutamine or [1-14C]glycine in isolated perfused rat liver persisted throughout a 15-min period of hypotonic exposure. Thus hypotonicity-induced alterations of mitochondrial metabolism apparently do not parallel the time course of mitochondrial volume changes. This suggests that persistent mitochondrial swelling is not required for functional alterations, but that the latter may be triggered by the initial swelling of mitochondria. Hypotonic exposure did not alter the nuclear volume of isolated hepatocytes. Cell membrane surface nearly doubled after 5 min of hypotonic exposure, but returned within 15 min of exposure to values observed in normotonic media. This may reflect the participation of exocytosis in hepatocyte volume regulation.

Animals↗
PubMed1993

Hyperosmolality regulates endothelin release by Madin-Darby canine kidney cells.

ET release by the renal epithelial Madin-Darby canine kidney (MDCK) cell line was investigated under isosmotic (300 mosmol/kg H2O; pH 7.4) and hyperosmotic (400, 500, or 600 mosmol/kg H2O) culture and assay conditions by the use of a specific and sensitive RIA. During isosmotic incubation, MDCK cells, which may be of collecting duct origin, secreted by far more ET into the cell culture supernatant (495.7 +/- 25.5 fmol.mg of protein-1.24 h-1) than did the proximal tubule-derived LLC-PK1 (2.42 +/- 0.20 fmol.mg of protein-1.24 h-1) and opossum kidney (3.12 +/- 0.47 fmol.mg of protein-1.24 h-1) cells. ET secretion by MDCK monolayers increased progressively within 24 h and then only slightly declined up to 48 h. Phosphoramidon (100 mumol/L) inhibited the constitutive ET synthesis in MDCK cells by 60%, indicating the participation of a phosphoramidon-sensitive ET-converting enzyme in the processing of bigET to ET in these cells. MDCK epithelia grown on filter inserts showed a clear polarity in their ET release. The baseline secretion of ET was 2.5 times higher to the basolateral than to the apical side, which might be in support of a predominantly basolateral action of the peptide. Short-term incubation of MDCK cells in hyperosmotic NaCl media for 24 h dose dependently decreased ET production. When urea was used as the solute to generate hyperosmolality, ET release by MDCK cells significantly increased. In contrast, when raffinose was added to increase osmolality to 500 mosmol/kg H2O, a decrease of ET production in a range similar to the effect of NaCl was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

In vitro and in vivo effect of antibiotics on catheters colonized by staphylococci.

An in vitro model was used to study whether and how catheter infections can be cured. Silastic catheters were "infected" with Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis KH11 and V2; these "infections" were then treated with 24, 48 and 96 h continuous infusions of various antimicrobial agents administered both as monotherapy and in combination. The Staphylococcus aureus strain was considerably more difficult to eliminate from catheters than were the Staphylococcus epidermidis strains. This experience gained in the laboratory was then applied in vivo to 16 episodes of catheter sepsis in seven children. Treatment for at least six days with imipenem/cilastatin combined with fosfomycin or an aminoglycoside successfully eliminated the pathogens isolated from 11 of the 16 episodes of infection. The broad-spectrum combination was chosen because it could not be assumed that individual pathogens would be sensitive to a single substance. Nine of the infected catheters could be retained in the patients. This experience suggests that it may be possible to successfully eliminate the colonization of central venous catheters by coagulase-negative staphylococci using the antimicrobial agents employed here.

Anti-Bacterial Agents↗
PubMed1992

Tissue distribution of neutrophils in postischemic acute renal failure.

Polymorphonuclear neutrophil granulocytes (PMNs) seem to participate in the pathogenesis of renal ischemic reperfusion injury. The kidneys from male Sprague Dawley rats were immersion-fixed after 45 min of renal artery clamping followed by reperfusion for 0, 5, 20, and 120 min, respectively. The tissue distribution of PMNs in the kidneys was studied histochemically using naphthol AS-D chloroacetate esterase as a specific marker for these cells. Neutrophil counts per unit sectional area were obtained for renal cortex, outer and inner medulla. In the cortex separate intraglomerular and peritubular counts, and in the outer medulla separate outer and inner stripe counts were made. After 120 min of reperfusion the total renal PMN counts were 488 +/- 62 (n = 4) compared with 54 +/- 4 (n = 4) per cm2 in nonischemic controls. Within 120 min of reperfusion PMN counts increased by a factor of 8 in the cortex, of 12 in the outer medulla and of 14 in the inner medulla, compared with controls. The ratio of intraglomerular against peritubular PMN counts was approximately 2 in controls, but 0.5 after a 120-min reperfusion interval. The outer stripe of the outer medulla contained only a small number of PMNs whereas PMN counts of 923 +/- 197 (n = 4) per cm2 were found in the inner stripe after 120 min reperfusion. Interestingly, there was a marked increase in PMNs in the inner stripe during the first 5 min of reperfusion but no extravasation of PMNs was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1992

Ammoniagenesis in LLC-PK1 cultures: role of transamination.

The LLC-PK1 renal epithelial cell line has been used as a model system to study renal ammoniagenesis and its regulation by metabolic acidosis in vitro. Experiments were performed on confluent LLC-PK1 epithelia grown for 10-14 days in conventional monolayer technique. After the medium pH was changed from 7.6 to 7.0 for 24-72 h by lowering the bicarbonate concentration in culture medium, LLC-PK1 cells responded with an adaptive increase in glutamine consumption and ammonia production. The rates of glutamine uptake and ammonia generation displayed a ratio of 1:1, i.e., 1 mol ammonia was produced per mole of glutamine consumed. Glutamine consumption and ammonia formation were paralleled by an equimolar production of L-alanine, indicating that transamination appears to be the main ammoniagenic pathway in LLC-PK1 cells. Analysis of the key enzymes of renal ammoniagenesis, phosphate-dependent glutaminase (PDG) and glutamate dehydrogenase (GDH), revealed no changes in enzyme activities up to 72 h of adaptation. Alanine aminotransferase (ALT) activity in LLC-PK1 cells also remained unchanged during the adaptation period. Because transamination seems to play a crucial role in channeling the metabolic flux in LLC-PK1 ammoniagenesis, experiments were performed in which transamination was inhibited by (aminooxy)acetate (AOA). After incubation of control and pH 7.0-adapted LLC-PK1 cultures for 24-72 h in 0.2 mM AOA, no alanine production was found, but 2 mol of ammonia were formed per mole of glutamine consumed, again, without adaptive changes in PDG and GDH activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1990

Morphology of the differentiation and maturation of LLC-PK1 epithelia.

In the present study, a stereologic approach was utilized to quantitatively assess morphological changes during the differentiation of LLC-PK1 cells into an epithelial membrane. This renal epithelial cell line has been described to undergo morphological changes during differentiation and maturation from subconfluent culture to a confluent epithelial layer. An increase in the number of apical microvilli, interpreted as an areal increase in this membrane domain was reported. This morphological differentiation was found to be accompanied by an increase in the expression of apical Na(+)-dependent hexose transport and the activities of certain brush border enzymes. Since no data are available that quantify the morphologic changes during LLC-PK1 differentiation, a quantitative morphologic-stereologic-investigation was performed for an early (6 days) and a late (12 days) state of confluence of LLC-PK1 monolayer cultures. The following morphological parameters were determined by light and electron microscopic morphometry: volume fractions (Vv) of nuclei, mitochondria, and lysosomes, and surface densities (Sv) of the apical and basolateral cell membrane domains. For the apical membrane surface, the microvillous fraction has been measured separately. Since the stereologic approach used in the present study allows the determination of absolute cell volumes, the absolute measures of organelle volumes (V) and membrane surfaces (S) per average cell can be calculated from volume and surface densities. Although no changes in cell density were found for 6 and 12 day old LLC-PK1 monolayers, indicating ceased cell proliferation due to contact inhibition, remarkable changes were found concerning the absolute cell volume and apical membrane surface. The observed increase in the apical cell surface was exclusively due to the enlarged microvillous surface fraction. This finding is in good agreement with the increased number of Na(+)-dependent hexose transporters as well as with the increased expression of apical membrane marker enzymes observed during the differentiation of LLC-PK1 monolayers.

Animals↗
PubMed1990

Madin-Darby canine kidney cells. III. Aldosterone stimulates an apical H+/K+ pump.

Functionally and morphologically, Madin-Darby canine kidney (MDCK) cells resemble intercalated cells of urinary epithelia. Experiments were performed on domes of confluent MDCK monolayers to test for apical H+ secretion. Apical application of 10(-3) mol/l amiloride or of Na(+)-free solution significantly reduced the limiting pH gradient across the dome epithelium (delta pHd) consistent with inhibition of apical Na+/H+ exchange. Short-circuit current (SCC) measurements disclosed an acetazolamide-sensitive, (basolateral to apical) positive transepithelial current stimulated by 10(-7) mol/l aldosterone and inhibited by acidification of apical medium to pH = 4.5. Histochemical evaluation of carbonic anhydrase (CA) activity revealed cytoplasmic and apical-membrane-bound CA particularly in dome-forming cells. Apical substitution of Na+ by K+ increased delta pHd, whereas a reduction of K+ concentration to 0.5 mmol/l or addition of barium or omeprazole (10(-5) mol/l) to the apical superfusate reduced delta pHd by at least 75%. Aldosterone-stimulated SCC was completely abolished by the apical application of barium. We conclude that besides Na+/H+ exchange MDCK cells can express an apically located H(+)-K+ pump stimulated by aldosterone and inhibited directly by the anti-ulcer agent omeprazole or indirectly, either by blocking apical K+ recycling or by interfering with the CA-dependent intracellular formation of H+ ions.

Aldosterone↗
PubMed1990

Morphology of renal tubular damage from nephrotoxins.

The proximal renal tubular cells' vulnerability to the direct toxic action of chemicals is largely due to the role played by this nephron portion in absorption and secretion. This is an energy-demanding function so that these cells must have a high rate of oxidative metabolism and thus contain many mitochondria supplying the Na+/K+ pumps at the basolateral plasma membrane domain, thereby driving the carrier systems for entry of water and solutes across the luminal membrane. Thus toxic mechanisms leading directly or indirectly to disturbances of the renal cells' energy metabolism will result in cell injury and acute renal insufficiency. Quantitative morphological-stereological-analysis of at least two, the mercuric chloride- and the maleate-induced experimental models of toxic acute renal failure, show a very early substantial loss of ATP-generating mitochondrial inner membrane surface as well as substantial decrease in those functions protecting cells against oxidative or auto-oxidative processes, i.e. glutathione content, activities of the free-radical-scavenging systems superoxide dismutase, glutathione peroxidase and glutathione reductase and catalase. The cellular dysfunction following these early events may be considered as causative of the subsequent development of most of the morphological alterations described, which are fairly similar in appearance regardless of the toxic principle acting upon the kidney.

Acute Kidney Injury↗
PubMed1990

Xanthine oxidase: evidence against a causative role in renal reperfusion injury.

The conversion rates of xanthine dehydrogenase (XDH) to xanthine oxidase (XO) were compared with the time course of in vivo lipid peroxidation (LPO) in an ischemia-reperfusion model of acute renal failure in the rat. LPO, measured as the renal release of malondialdehyde (MDA), was found to be markedly elevated only during the first 5 min of blood reflow following a 45-min interval of ischemia (arteriovenous MDA difference -277.3 +/- 53.5 vs. 3.7 +/- 5.7 nmol/l in controls, n = 14). After 30 min of reperfusion, arteriovenous MDA differences nearly reached control values (9.7 +/- 31.8 nmol/l, n = 7). In contrast to enhanced LPO, no significant conversion of XDH to XO was found (XO activity in controls: 23 +/- 1% of XO plus XDH activity vs. 26 +/- 3% after 45 min of ischemia, n = 7). Therefore XO-derived superoxide anion radicals cannot be considered causative for LPO in the reperfusion interval of experimental ischemic acute renal failure.

Animals↗
PubMed1989

Fusion of cultured dog kidney (MDCK) cells: I. Technique, fate of plasma membranes and of cell nuclei.

The evaluation of the intracellular signal train and its regulatory function in controlling transepithelial transport with electrophysiological methods often requires intracellular measurements with microelectrodes. However, multiple impalements in epithelial cells are hampered by the small size of the cells. In an attempt to avoid these problems we fused cells of an established cell line. Madin Darby canine kidney cells, originally derived from dog kidney, to "giant" cells by applying a modified polyethylene glycol method. During trypsin-induced detachment from the ground of the petri dish, individual cells grown in a monolayer incorporate volume and mainly lose basolateral plasma membrane by extrusion. By isovolumetric cell-to-cell fusion, spherical "giant" cells are formed within 2 hr. During this process a major part of the individual cell plasma membranes is internalized. Over three weeks following cell plasma membrane fusion degradation of single cell nuclei and cell nuclear fusion occurs. We conclude that this experimental approach opens the possibility to investigate ion transport of epithelia in culture by somatic cell genetic techniques.

Animals↗
PubMed1988

Noninvasive diagnosis of renal allograft rejections--application of an information-theoretical model.

This paper describes an information-theoretical model developed for detection of renal allograft rejection on the basis of various laboratory data. In this report the mathematical background of the model is described in detail and the rationale of its use is discussed. An example is given for the practical application of the model in kidney grafted patients. In the 30 patients of the test collective, seven rejection episodes were diagnosed by the clinicians and verified histologically. All seven rejection episodes were detected by the model, in the mean 2.4 days (median; 3 days) before the clinical diagnosis.

Biopsy, Needle↗
PubMed1988

Toxic properties of the mushroom Cortinarius orellanus. I. Chemical characterization of the main toxin of Cortinarius orellanus (Fries) and Cortinarius speciosissimus (Kühn & Romagn) and acute toxicity in mice.

The toxins of the mushrooms Cortinarius orellanus (Fries) and Cortinarius speciosissimus (Kühn & Romagn) were isolated by extraction procedures and Sephadex chromatography. All intermediate and end products of the purification process were tested in mice for acute toxicity after oral and i.p. administration. In both species a fluorescent main toxin and a nonfluorescent compound of minor toxicity were found. The main toxin of both species was identified by mass spectrometric and nuclear magnetic resonance analyses as the 2,2'-bipyridine-3,3',4,4'-tetrol-1,1'-dioxide, which is identical to orellanine. The purified compound was toxic when administered either orally or i.p. When given orally the LD50 was 33 mg/kg body weight in mice. The oral LD50 of Cortinarius orellanus (2.20 g dried mushroom/kg) and of Cortinarius speciosissimus (3.12 g/kg) depended on the orellanine content (14 mg/g in Cortinarius orellanus and 9 mg/g in Cortinarius speciosissimus). The second toxic component was ineffective in mice when given orally. It caused acute toxicity when administered i.p., but toxicity was low when compared to the main toxin. Thus it appears to be of minor importance. Intraperitoneal testing of both isolated toxins and of the extract containing the whole toxic potential of the mushrooms revealed that toxicity, time dependency and expression of toxicosis is accounted for by the sum of these two toxins. No peptidic main toxin as described by other mycologists could be detected.

2,2'-Dipyridyl↗
PubMed1988

Toxic properties of the mushroom Cortinarius orellanus (Fries). II. Impairment of renal function in rats.

Oral administration of the toxic mushroom Cortinarius orellanus (Fr.) to male Sprague Dawley rats caused serious impairment of renal function. The signs observed were similar to those produced in humans who ingest this fungus. Administration of 2.0 g dried Cortinarius orellanus per kg body weight led to acute renal dysfunction within 48 h. The pattern of impairment included reduced glomerular filtration rate, decreased renal absorption of water, sodium and potassium, and proteinuria and glucosuria. The nephrotoxic effect was further characterized by decreased activities of the brush border enzymes alkaline phosphatase and gamma-glutamyltranspeptidase in urine, despite a remarkable increase in protein excretion of predominantly tubular origin. These findings were substantiated by morphologic changes, which could be detected as early as 12 h after dosing. Morphologically discernible signs of renal tubular damage start with deformation of the proximal tubular brush border region. Within 48 h after toxin ingestion, prenecrotic and necrotic cells could be found in all nephron segments contained in the renal cortex. The most prominent changes were a vesiculation of the apical cell pole and a swelling of the smooth surfaced endoplasmic reticulum and of mitochondria. The latter was accompanied by a loss in matrix material and a massive fragmentation of mitochondrial cristae membranes. Detectable quantities of the toxic principle of the mushroom, orellanine, were excreted only within the first 24 h after dosing. No impairment of liver function was detected.

Agaricales↗