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R Nilius

Publications and source records attributed to R Nilius.

At least 19 recordsLinked to original sources
PubMed1999

Effects of twelve months ethanol feeding on rat liver metabolic activity.

Thirty male Wistar rats were fed with 15% ethanol (V/V) for one year. Thirty other male animals were the control group. To determine the possible metabolic disturbances caused by chronic ethanol feeding in blood we measured in blood metabolic parameters, and in a liver perfusion assay the hepatic insulin clearance and hepatic urea production in these animals. Between the ethanol-fed and the control animals there were significant differences in the following parameters: blood insulin concentration (47 vs. 2 microU/ml) and activities of amino acid transferases in liver homogenates at the end of the perfusion experiments (ASAT, 5950 vs. 70; ALAT, 3632 vs. 93 U/l). The other parameters were still normal in the ethanol-fed animals. Thus in these experiments after 12 months of 15% (V/V) ethanol feeding the rats still showed only a state of beginning metabolic disturbances in the liver. The results are discussed under consideration of the formation of acetaldehyde protein adducts in all rat organs investigated, namely, liver, kidney, heart and skeleton muscle, gut and spleen.

Acetaldehyde↗
PubMed1998

Occurrence of acetaldehyde protein adducts formed in various organs of chronically ethanol fed rats: an immunohistochemical study.

We investigated the pathophysiological role of acetaldehyde protein adducts formed in vivo in organs of chronically alcohol fed male Wistar rats. Thirty male Wistar rats were fed on rodent pellets and 15% alcohol (V/V) for 5, 8 and 12 months, respectively before they were sacrificed. Further 30 male rats were chosen as the control group. We tested several organs by histological and immunohistochemical methods. Using immunohistological analysis, in the 12 months groups the basal membranes of glomerula, the membranes of liver, skeleton muscle and heart cells, and the gut were stained positively for acetaldehyde adducts. Using Western blotting of liver cell fractions (mitochondria/ lysosomes; microsomes; cytosol) adducts in charateristic molecular weight regions were detected. Approximately 30% of the sera of experimental rats contained antibodies against the acetaldehyde adducts formed in vivo. Immunologically detectable acetaldehyde adducts could be found in all rat organs tested. The stage of alcohol disease attained in this experiment after 12 months of ethanol feeding is described as the initial phase of manifestations of disturbances that are seen also in the carbohydrate metabolism.

Acetaldehyde↗
PubMed1997

Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study.

One hundred twenty-six patients with cirrhosis, hyperammonemia (>50 micromol/L), and chronic (persistent) hepatic encephalopathy (HE), which developed spontaneously without the existence of known precipitating factors, were enrolled in a randomized, double-blind, placebo-controlled clinical trial of intravenously administered L-ornithine-L-aspartate (OA). Patients with subclinical (grade 0, West-Haven criteria) hepatic encephalopathy (SHE), characterized by a prolonged number connection test A (NCT-A) time, and manifest HE (grades I and II, West-Haven criteria) were included in the investigation. The trial was planned as a confirmatory clinical trial OA administered in a dose of 20 g/d, as well as placebo, were dissolved in 250 mL of 5% fructose and infused intravenously for a period of 4 hours during 7 consecutive days with a superimposed protein load at the end of the daily treatment period. Primary variables were postprandial venous ammonia and NCT-A performance time measured following OA or placebo infusions to evaluate the net effect of the treatment on the prevention of the protein-induced hyperammonemia, and on parameters such as NCT-A influenced by hyperammonemia. Mental state gradation, portal systemic encephalopathy index (PSEI), and fasting ammonia levels were estimated as additional efficacy parameters. The data presented are based on the total study sample (intent-to-treat analysis), which included 63 patients in the placebo group and 63 patients in the OA group. Of the 126 patients, 114 met all the criteria for inclusion and completed the trial and treatment as outlined in the protocol (treated-per-protocol analysis). During baseline, the placebo and treatment groups were homogeneous with regard to mental states, NCT-A performance time, fasting venous blood ammonia levels, and Child-Pugh criteria. Although a slight improvement occurred in the placebo group, NCT-A performance times (P < .001) and postprandial venous ammonia concentrations in the OA-treated group showed improvements in comparison with placebo. In addition, venous fasting blood ammonia concentration (P < .01), mental state gradation (P < .001), and PSEI (P < .01), which includes the mental state gradation, NCT-A time, and postprandial venous ammonia in this trial, improved to a much higher degree in the OA group than in the placebo group. In subgroups retrospectively classified according to their initial mental state gradation, OA showed differential but uniformly significant efficacies in patients with manifest HE with respect to ammonia-lowering, improvement in NCT times, and mental state gradation. In patients with initial SHE, OA revealed differences between the medications in the psychometric test used. Adverse events consisting of mild gastrointestinal disturbances were observed in 3 of the OA-treated patients (5%). OA infusion appears to be a safe, effective treatment of chronic (persistent) manifest HE in cirrhotic patients. Additional investigations are required to assess the efficacy of OA in patients with SHE, as well as in patients with more severe grades of HE.

Adult↗
PubMed1997

A histochemical study of the distribution of dextran 500 in human corneas during organ culture.

PURPOSE: The aim of this histochemical study was to demonstrate the absorption of dextran 500 and its distribution in the cornea after storage under standard eye bank conditions. Furthermore, an attempt was made to distinguish between the soluble and insoluble parts of dextran 500 absorbed by the cornea, in order to see how much dextran remains in the cornea after transplantation. METHODS: Forty-nine fresh and 65 organ-cultured human corneas were investigated. The corneas were cultured for 28 days in a dextran-free medium, followed by a period of 1-14 days in a medium containing 5% dextran 500. Cryosections were stained by aqueous PAS and a modified alcoholic PAS to determine the amount of dextran. RESULTS: Dextran was not found in the epithelium, stroma or endothelium of fresh human corneas. By contrast, extra- and intracellular positive staining reactions were detected in corneas following storage in a medium containing dextran. Dextran 500 absorption was relatively diffuse in the epithelium after storage in a dextran medium. Initial accumulations were found in the stroma near Bowman's and Descemet's membranes and also in the central part of the cornea, as the period of culture in the medium containing dextran lengthened. We also observed interaction between the stroma and endothelium: decreasing amounts in the endothelium were followed by an increase of same in the stroma. Intracellular deposits of dextran were detected after only one day. A much greater part of the extracellular dextran than previously described was found to be insoluble. CONCLUSIONS: As the amount of dextran in the cornea increases over a longer storage time, we conclude that the period of storage in a medium containing dextran should be limited to four days. The fact that the cornea is saturated with dextran after seven days has been shown in further studies to interfere with mitochondrial function and may also cause severe post-operative swelling of the transplant, hence leading to a longer recovery period for the patient.

Cornea↗
PubMed1993

[Endogenous digitalis-like factor in liver cirrhosis and cholestasis].

Endogenous digitalis-like factor (EDLF), an inhibitor of membrane Na+/K(+)-ATPase, is discussed to be involved in the pathogenesis of cirrhogenic portal hypertension, ascites formation and development of functional hepatorenal failure. Therefore, we investigated the serum content of this mediator in patients with liver cirrhosis Child-Pugh stage A, B, and C (n = 27) by means of enzyme immunoassay with a specific digoxin antibody. Furthermore, a correlation analysis was performed in order to find out correlations between signs of cell injury, cholestasis, synthetic cell function, ascites formation, and hepatorenal failure. Our results demonstrate that EDLF is significantly elevated in Child C cirrhosis (0.61 +/- 0.15 ng/ml) in comparison to Child A cirrhosis (0.013 +/- 0.2 ng/ml) and is also higher than in Child B cirrhosis (0.23 +/- 0.25 ng/ml). In patients without ascites EDLF (0.056 +/- 0.19 ng/ml) differs significantly from that of patients with non-complicated ascites (0.156 +/- 0.176 ng/ml) and from that of patients with therapy refractory ascites (0.66 +/- 0.17 ng/ml) or hepatorenal failure (1.56 ng/ml). There are no correlations between EDLF and renal function. Significant correlations were demonstrated for cholestasis (serum bilirubin), synthesis function (serum protein, Quick's value, cholinesterase, fibrinogen, albumin), and the degree of portasystemic encephalopathy (number connection test). We conclude that EDLF may act as a mediator in the process of progressive portal hypertension and its complications due to cirrhosis. This process of progression is caused by the inhibition of Na+/K(+)-ATPase, vasoconstriction, and endothelin secretion.

Adult↗
PubMed1993

[Rational laboratory diagnosis of cholestasis syndrome].

Laboratory diagnostics efficiently applied is of decisive importance for a great deal of questions in spite of the technical and endoscopic methods which are available today in the field of examinations. By means of a screening programme consisting of ALAT, gamma-GT, ChE at a sensitivity of > 90% alterations in both the hepatobiliary system and cholestasis can be recognized with sufficient reliability. Clinical data and a defined laboratory routine programme as a second step in diagnostics results in reliable indication for distinction between obstructive and non-obstructive cholestasis which can be promoted by computer-aided techniques. On the basis of such pre-selections special laboratory methods (differential diagnosis of consecutive non-obstructive cholestasis in liver diseases) or invasive methods to clarify their reason and localization diagnostics of biliary obstruction can then be applied in a well-directed manner to obtain a definite nosologic diagnosis. Effective diagnostic procedures in this three-step programme are described.

Alanine Transaminase↗
PubMed1993

[The prognostic value of serochemical cholestasis parameters in liver cirrhosis].

In a semiprospective study on the prognosis of liver cirrhosis we investigated whether common, selected cholestasis parameters in liver diagnostics are associated with the survival time and the probability of survival and whether they permit prognostic statements. In 93 patients with liver cirrhosis of different aetiology the serum-bilirubin, gamma-GT, AP and AAP were determined for this purpose and applied in the same way as a clinically proven icterus to the survival time of the patients. The mean time of observation was 13.8 years (+/- 1.9 years). In the simple correlation matrix none of the cholestasis parameters correlated with the survival time. There was no difference in the frequency with which deceased and surviving patients suffered from icterus and, with the exception of AAP, there was no different serum concentration of the cholestasis parameters according to univariate analysis. However, icterus in the early phase of the observation time and increased gamma-GT (over 3000 nmol/l.s) in the late phase of observation were associated with a reduced probability of survival. Correspondingly, the serum-bilirubin of deceased patients (only slightly) correlated in the simple linear regression with their survival time. In multivariate analysis gamma-GT proved to be non-redundant for the estimation of the patients' probability of survival.

Adult↗
PubMed1992

[Endoscopic sclerosing of esophageal varices--technique, possibilities and limits of the method].

The paper intends to give a survey of the significance of endoscopic sclerotherapy in gastro-esophageal varices. The control of an acute bleeding can be achieved in a high percentage (70-95%). However, the hospital mortality has persisted in 30% depending on early rebleeding episodes and alterations in hepatic function. Controlled trials have confirmed a lowering of rebleeding risk as well as an improved survival by repeated sclerotherapy. The effectiveness of prophylactic sclerosing before the first bleeding is uncertain because of contrary results published. A prophylactic application seems to be favourable in patients at high risk of bleeding only.

Esophageal and Gastric Varices↗
PubMed1991

Changes of dipeptidylpeptidase IV as a membrane marker of lymphocytes in acute and chronic liver diseases--biochemical and cytochemical investigations.

Lymphocytic dipeptidylpeptidase IV (DPP-IV, E.C. 3.4.14.5) is described as a marker enzyme of immunostimulant T-lymphocytes as well as functional characteristic of interleukin-2-producing cells. Cytochemical staining of DPP-IV positive lymphocytes and measurements of DPP-IV activity in mononuclear cells and in sera of patients suffering from different kinds of liver diseases were performed to evaluate the average activities in positive cells. The results demonstrated that this serine exopeptidase exhibits extremely low activity in autoimmune chronic hepatopathies. On the contrary, hepatitis-B-associated liver diseases were connected with markedly increased values. Furthermore, significant differences of DPP-IV activity were found in different kinds of acute and chronic liver diseases. These findings are discussed in connection with the participation of dipeptidylpeptidase IV in impaired immunoregulation of the altered liver.

Acute Disease↗
PubMed1991

[Portal hypertensive gastropathy--a rare cause of upper gastrointestinal hemorrhage].

There is evidence that the portal-hypertensive gastropathy is a clinical complication of portal hypertension and a distinct clinical entity being different from various types of gastritis. According to endoscopical findings one can differentiate 4 stages: I = superficial reddening on the surface of the gastric rugae, II = white reticular pattern separating areas of prominent pink oedematous mucosa (snake-skin or mosaic pattern), III = cherry red spots, IV = diffuse bleeding. These alterations occurring more prominently in the gastric fundus are caused by venous and capillary ectasia and by arteriovenous shunts. The potential of diffuse mucosal bleeding distinct from variceal haemorrhage is of clinical importance. Additionally, congestive mucosa seems to be more vulnerable to noxious agents in the gastric lumen. For therapy propranolol has been recommended.

Endothelium, Vascular↗
PubMed1991

Development of the low-T3-syndrome and prognosis assessment in patients with liver cirrhosis.

The aim of our study is to prove whether the development of the low-T3-syndrome in patients with liver cirrhosis is associated with their prognosis. For this purpose we determined the peripheral thyroid hormone levels in 28 patients with liver cirrhosis. For prognosis assessment we calculated the Prognostic Index (PI) on the basis of Cox's regression model as recently described by us. Calculating this index we used 11 parameters: liver morphology, consciousness, spider naevi, PCV, thrombocytes, gamma-GT, cholesterol, albumin, Quick's value, IgA, and potassium. It is demonstrated that there is an inverse correlation between T3-serum levels and PI (p = 0.03). An association could not be detected neither between reverse T3 and PI nor between T3 and rT3. On the other hand basal TSH was also inversely associated with PI. Thus, the low T3-serum levels did not induce a rise of basal TSH in cirrhotics. Moreover, the mean serum-T3-concentration differed significantly from that of 6 decreased patients and from that of the surviving (p = 0.00076). It seems to be true that low T3-serum levels are a very sensitive parameter for prognosis prediction in patients with liver cirrhosis.

Female↗
PubMed1991

[Pathogenesis and therapy of ascites in liver cirrhosis].

This paper reviews pathogenetic factors which contribute to the development of therapy-resistant ascites in liver cirrhosis. Main principles are known as "Overfilling"--and "Underfilling"-hypotheses followed by disturbances of different kinds of mediators influencing renal blood flow and natriuresis. The endpoint of a cascade is the development of a hepatorenal syndrome which is connected with therapeutic resistance against diuretics. Therefore, other therapeutic methods (paracentesis, reinfusion) must be taken in to account in order to improve prognosis of such cases.

Acute Kidney Injury↗
PubMed1991

Hepatic aldehyde dehydrogenase (E.C. 1.2.1.3.) isoenzymes and malondialdehyde levels in alcoholic liver disease.

To clarify the controversially discussed behaviour of hepatic ALDH isozymes in different liver diseases, 98 liver biopsy specimens were investigated as to their total ALDH and their isozyme activity. Simultaneously the malondialdehyde (MDA) content was measured in both biopsy samples and serum. The results show a significant decrease of the "low Km" isozyme E-2 activity depending on the severity of the liver disease. The tendency for the E-2 activity to decrease was greater in alcoholic than in nonalcoholic liver diseases. Although in all our diagnosis groups elevated MDA concentrations could be measured in both serum and liver tissue, a direct specific inhibitory effect on the E-2 activity could not be confirmed. The change from the low Km pathway to the high Km pathway of aldehyde detoxification, however, may contribute to the progress in alcoholic liver disease.

Aldehyde Dehydrogenase↗
PubMed1990

Prophylactic endoscopic sclerotherapy of esophageal varices--a prospective randomized trial.

Sixty-three patients with degree III or IV esophageal varices and the so-called red color sign, but without previous bleeding were randomly assigned to either prophylactic sclerotherapy (PST) (n = 30) or to a control group (n = 33). In 58 cases the portal hypertension was caused by liver cirrhosis (40% alcoholics). The two groups were comparable with respect to demographic data and endoscopic appearance, causes and severity of liver damage. Sclerotherapy was performed as combined intra-and paravariceal injections of 2 or 3% polidocanol. All patients, both in the treatment and in the control groups, who bled from varices after randomization, received sclerotherapy until the varices were eradicated, and remained in their groups. After a mean follow-up of 44.5 months, the bleeding rate in the PST group was significantly lower (30% vs 75%, p less than 0.01). The difference became significant from the second year onward. Fourteen patients of the PST group and 19 of the controls died (4 and 14, respectively, p less than 0.05 as a result of the bleeding). Life table analysis (Kaplan-Meier) revealed no differences in survival between the two groups. At the present time PST cannot yet be recommended as a method for clinical routine use.

Adult↗
PubMed1990

[Dipeptidylpeptidase IV activity in human lymphocytes in hepatobiliary diseases].

Lymphocytic dipeptidylaminopeptidase IV (DP-IV; E.C.3.4.14.5.) is described as a marker enzyme of immunostimulant T-lymphocytes as well as functional characteristic of IL-2-producing cells. Mononuclear cells of periphere blood (MNC) were isolated by density gradient centrifugation followed by enzymcytochemical staining of DP-IV positive cells and measuring of DP-IV enzyme activity using chromogenic substrates. As relative sign of single cell DP-IV activity we calculated average DP-IV activities of DP-IV positive cells. Blood samples from 14 patients with acute virus hepatitis, 30 cases of chronic active liver disease, 61 cases with liver cirrhosis of various kind and 19 patients with fatty liver and toxic hepatitis were investigated. As standard of comparison we used a group of healthy blood donors. By this way significant differences of described DP-IV parameters between some groups of liver disease were evident. Using an aetiologic classification of investigated liver diseases we found highly significant increased single cell activities in hepatitis-B associated cases in comparison to remarkable lower lower values in autoimmune cases. Different hypothesis about changes of lymphocytic dipeptidylaminopeptidase IV as a part of disturbed immunoregulation in chronic liver diseases were discussed.

Chemical and Drug Induced Liver Injury↗
PubMed1990

[Aldehyde-dehydrogenase from human liver: Purification, partial characterization and influence of malondialdehyde].

A procedure to separate the isozymes E1 and E2 of aldehyde dehydrogenase (ALDH, aldehyde: NAD oxidoreductase, EC 1.2.1.3) from human liver, avoiding 5'-AMP-Sepharose, was worked out. It results in fairly purified isozymes. The isoelectric points could be re-estimated for E1 at pH 5.21 +/- 0.04 and for E2 at pH 4.90 +/- 0.05. The pH-optimum of both the isozymes is dependent on the buffer used, the best buffer being sodium pyrophosphate/HCI. In this buffer the enzyme activity is also dependent on ionic strength. Malondialdehyde (MDA), at concentrations which are found in patient serum, is converted by the ALDH. The Km-values of this reaction are 1.71 mmol/l for MDA and 0.19 mmol/l for NAD (E1) and 0.21 mmol/l for MDA and 0.24 mmol/l for NAD (E2) resp. The highest rates of conversion are reached at concentrations of 0.08 mmol/l MDA (E1) and 0.16 mmol/l MDA (E2). At higher concentrations of MDA substrate excess inhibition is observed (Kss = 0.17 mmol/l for E1 and 0.20 mmol/l for E2).

Aldehyde Dehydrogenase↗
PubMed1990

[Ultrasound-controlled cutting biopsy for collecting histologic specimens].

The fine-needle puncture under ultrasound guidance has the disadvantage that the material obtained can only be evaluated by cytology. The cutting biopsy cannula represents a compromise between the fine and the Menghini needle. In this way, small tissue cylinders can be attained. The aim of the present study was to investigate to what extent the sampled specimen could be assessed by cytology or histology. Fine-needle puncture resulted in 22 (69%) out of 32 cases in material suitable for cytology. Cutting biopsy led in 34 out of 36 cases (94%) to specimen valid for histology. Thus, cutting biopsy clearly extends our diagnostic tools. It is not yet clear at present whether procedures with a higher risk - such as the Menghini puncture - can be in part replaced by alternative ones.

Biopsy↗