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S Mitzner

Publications and source records attributed to S Mitzner.

At least 19 recordsLinked to original sources
PubMed2005

[Extracorporeal blood purification in severe liver failure with the albumin dialysis MARS -- impact on relevant intensive care parameters].

Extracorporeal liver support methods have been tested for over 50 years now. Standard techniques of blood purification like dialysis, adsorption, hemo- and plasma filtration as well as bioreactor-based approaches using liver cells or tissues have been used. Most clinical experience, however, is limited to use in acute liver failure (ALF). Since 1993, the Molecular Adsorbent Recirculating System (MARS) has been used clinically -- a system that combines dialysis, filtration and adsorption in a biocompatible method. Human serum albumin (HSA) acts as a selective molecular adsorbent binding protein-bound compounds like bile acids or bilirubin. These substances can contribute to the maintenance or even further aggravation of liver failure. They are linked with the pathogenesis of hyperdynamic hypotonic circulation, hepatic encephalopathy, hepatorenal syndrome, impaired hepatic protein synthesis, and intractable pruritus seen in chronic liver failure. HSA takes over the toxic substances from a patient's blood and passes through a remote detoxification process including bicarbonate-dialysis and a two-step adsorption. It is then recirculated in the patient's blood. Up to today, more than 4000 patients have been treated in approximately 16,000 single sessions. Thus, MARS represents the most frequently used liver support method at the present time. In addition to ALF, mainly acute decompensations of chronic liver failures (ACLF) have been treated. The impact of the extracorporeal treatment on relevant medical parameters of intensive care medicine is discussed with regard to the specific situation of the liver-failure patient (susceptibility to infection, atypical picture and course of infection, coagulation disorders and bleeding tendencies).

Acute Kidney Injury↗
PubMed2002

Improvement in central nervous system functions during treatment of liver failure with albumin dialysis MARS--a review of clinical, biochemical, and electrophysiological data.

The Molecular Adsorbent Recirculating System (MARS) is a nonbiological liver support method based on the principles of dialysis, filtration, and adsorption. It allows the safe and efficient removal of both albumin-bound and water-soluble toxic metabolites, including ammonia, aromatic amino acids, tryptophan, and related phenolic and indolic products, as well as benzodiazepines. A well-documented effect of the treatment is the improvement of the hemodynamic situation of decompensated chronic patients. Systemic vascular resistance, mean arterial pressure, cerebral blood flow, and cerebral oxygen consumption increased significantly. The degree of hepatic encephalopathy decreased significantly. Increased intracranial pressure could be normalized in both chronic and fulminant liver failure. In three randomized clinical trials significant improvement of survival could be demonstrated. In a model of murine neuronal networks cultured on multi-microelectrode array plates and incubated with plasma from liver failure patients, a normalization of the spike and burst pattern could be observed, if plasma samples from MARS-treated patients before and after treatment were compared. In conclusion, MARS significantly improves central nervous system functions. It can serve as a model for the further investigation of the role of protein-bound substances in hepatic encephalopathy and cerebral hemodynamics.

Brain↗
PubMed2002

Albumin dialysis: single pass vs. recirculation (MARS).

The single pass albumin dialysis (SPAD) was reported to be an alternative to the Molecular Adsorbent Recirculating System (MARS) for the effective removal of protein bound substances in liver failure. Three SPAD experiments using different albumin concentrations and dialysate flow rates were performed. In each experiment, 1000 ml human donor plasma, spiked with 250 mg unconjugated bilirubin, 200 mg sulfobromophthalein (BSP) and 115 mg glycocholic acid (N-[3alpha,7alpha,12alpha-trihydroxy-24-oxycholan-24-yl]glycine) - a conjugated bile acid (BA), circulated in a closed loop with 150 ml/min and was dialysed against albumin solution. These substances are bound to the different binding sites of albumin and have different association constants. For the comparison, the standard MARS experiment was performed using the same plasma flow rate of 150 ml/min. Moreover, the clearances of bilirubin for MARS and SPAD during clinical treatments were calculated using own data and those reported by Seige, Kreymann, Jeschke, et al. in Transplant Proc 1999; 31: 1371-5. The concentrations of bilirubin, BSP and BA were measured in plasma and dialysate and for these substances clearances (Cl) were calculated. It is known that the elimination rate of bilirubin is not very high during albumin dialysis in comparison to other substances, like bile acids, due to the high association constant. An increase of albumin concentration or the flow rate improved the efficacy but also raised the costs substantially. In this study, we have shown that MARS is the more effective kind of albumin dialysis for the important substances like bile acids. By SPAD an improvement of efficacy can be reached only by dramatic increase of the costs. Also, the earlier experiments showed that MARS is safer because of the removal of the stabilizers, which are normally included in the commercial albumin solutions.

Bile Acids and Salts↗
PubMed1998

Systemic long-term delivery of antibodies in immunocompetent animals using cellulose sulphate capsules containing antibody-producing cells.

Implantation of capsules containing antibody-producing cells into patients would potentially permit systemic long-term delivery of antibodies and might, thus, be useful in the development of surveillance treatments for cancers and severe viral diseases. We show that cellulose sulphate (CS) capsules containing hybridoma cells, when implanted subcutaneously or in the intraperitoneal cavity, can be used for delivering monoclonal antibodies into the blood-stream of immunocompetent mice for at least several months. In contrast to capsules implanted into the intraperitoneal cavity, which remain mobile and nonvascularized, capsules implanted under the skin form neo-organs which become vascularized within days. This may explain the higher blood concentration of the antibody we have observed in the latter case. Importantly, neither an isolating fibrosis nor an obvious inflammatory response was detected at the capsule implantation sites during observation periods as long as 10 months. Finally, no anti-idiotypic immune response against the ectopically delivered antibody was shown to occur. This rules out any potent adjuvant effect of the cellulose sulphate matrix that might have stimulated a neutralizing humoral response. Taken together, our data indicate that encapsulation of antibody-producing cells into CS might be used in antibody-based gene/cell therapy approaches.

Animals↗
PubMed1998

Targeted chemotherapy by intratumour injection of encapsulated cells engineered to produce CYP2B1, an ifosfamide activating cytochrome P450.

The prognosis of pancreatic adenocarcinoma is poor and current treatment ineffective. A novel treatment strategy is described here using a mouse model system for pancreatic cancer. Cells that have been genetically modified to express the cytochrome P450 2B1 enzyme are encapsulated in cellulose sulphate and implanted into pre-established tumours derived from human pancreatic cells. Cytochrome P450 2B1 converts the chemotherapeutic agent ifosfamide to toxic metabolites. Administration of ifosfamide to tumour-bearing mice that were recipients of implanted encapsulated cells results in partial or even complete tumour ablation. These results suggest that in situ chemotherapy with genetically modified cells in an immunoprotected environment may prove useful for application in man.

Adenocarcinoma↗
PubMed1996

Cell sources for bioartificial liver support.

The present review discusses hepatocyte sources for a bioartificial liver. Intended requirements for cell sources are for example: synthesis of plasma proteins, detoxification and regulation. The need for highly differentiated hepatocytes is stressed. Furthermore, the gap between this objective on the one hand and the real possibilities as they appear today on the other is shown. Alternatives to primarily isolated hepatocytes are discussed, thereby elucidating the limits of established cell lines. In summary, it is postulated that the results expected from a bioartificial liver, are closely related to the source and type of cells used.

Animals↗
PubMed1996

A carrier-mediated transport of toxins in a hybrid membrane. Safety barrier between a patients blood and a bioartificial liver.

Combination of detoxifying liver support systems with liver cell bioreactors may have additional benefits for the treatment of liver failure due to the replacement of known and unknown metabolic activities of the liver. However, the problem of side effects and possible risks caused by the use of animal hepatocytes or hepatoma cells remains unsolved which underlines the need of a safety barrier between the patients blood and the extracorporeal bioreactor. Passive filters do not meet the requirements of such membranes, because in liver failure desired and undesired molecules in the patients blood share similar physicochemical properties. That challenges the development of biologically designed separation membranes. A hybrid membrane is formed by implementation of transport proteins into a highly permeable hollow fiber. The transport of free solutes and albumin bound toxins is tested in vitro in comparison with conventional high flux membranes. The transport characteristics for tightly albumin bound toxins are significantly improved for the hybrid membrane. The transport of albumin bound toxins across the membrane is not associated with albumin. The selectivity of the transport is evaluated in vivo. No significant loss of middle molecular weight hormones attached to other carrier proteins was observed. Neither transport of immunologically relevant proteins across the membrane nor loss of valuable proteins was measured. Also in vivo, a significant reduction of protein bound toxins and a transport of metabolically relevant solutes, like amino acids, was shown. The presented hybrid membrane may be used like an "intelligent membrane" as a safety barrier between the patients blood and cell devices.

Amino Acids↗
PubMed1993

Extracorporeal endotoxin removal by immobilized polyethylenimine.

The neutralization of bacterial endotoxins (ET) is still an unsolved problem in therapeutic medicine. The efficacy of anti-endotoxin antibodies or receptor antagonists and other substances interfering with the endotoxin-induced pathomechanisms is dependent on an intact cellular degradation system of the host. However, the phagocytosis function of that system seems to be impaired regularly in patients with intense or long-lasting endotoxemia or septic shock and in patients undergoing hemodialysis. Extracorporeal adsorption of ET might well be an effective support in the anti-ET therapy by lowering the amount of circulating ET and thus relieving the defense system of the body. In this work a new ET-adsorbent based on macroporous cellulosic beads with immobilized polyethylenimine (PEI) was tested for its ET-removal capacity in vitro. A test solution with 100 ng/ml ET from Escherichia coli 055:B5 was recirculated in a system containing the adsorbent beads. Polymyxin B immobilized to the same carrier was used for comparison. PEI as well as polymyxin B showed complete removal of ET from plasma and water as was measured by the Limulus Amebocyte Lysate (LAL) test (Chromogenix). The biocompatibility of the PEI absorber was superior to that of polymyxin B. The results indicate that the PEI absorber is of high efficacy and possibly of interest for the treatment of endotoxemia.

Adsorption↗
PubMed1993

Dialysis against a recycled albumin solution enables the removal of albumin-bound toxins.

The removal of protein-bound substances of pathogenetic relevance from blood is of therapeutic interest for drug intoxications, renal and liver failure, and metabolic disorders. Current methods using adsorbents are effective but often not specific enough. This work presents an alternative method that enables the dialyzability of albumin-bound toxins from plasma by the use of a high-flux dialyzer (F 60 Fresenius) and an albumin solution circulating on the dialysate side to increase selectively the affinity for albumin-bound toxins. This method resulted in effective removal of unconjugated bilirubin, drugs with a high protein-binding ratio (sulfobromophthalein, theophylline), and a protein-bound toxin (phenol). The additional removal of PBS could extend the applicability of dialysis, for example, to drug intoxications and liver failure or could improve the elimination of protein-bound uremic toxins in chronic renal failure.

Adsorption↗
PubMed1993

Prolonged biochemical and morphological stability of encapsulated liver cells--a new method.

In this work a new type of polyelectrolyte complex capsules is introduced as an artificial housing for liver cells. Male Wistar rat hepatocytes were encapsulated using cellulose sulphate and polydimethyldialyllammonium chloride as polyelectrolytes. Amino acid metabolism rate and urea synthesis of the cells increased over the investigation period in contrast to the decrease observed in control monolayer cultures. The encapsulated cells were morphologically characterized. The described procedure represents a sufficient method for the cultivation of living cells in mechanically stable semipermeable microcapsules.

Amino Acids↗
PubMed1991

Importance of endotoxins in high-flux dialysis.

Endotoxins are not only important for inducing pyrogenic reactions during haemodialysis but also for the stimulation of different blood cells. This is followed by the release of interleukin-1 and other powerful biological active substances, resulting in a broad spectrum of biological activities. Permeation of LPS (endotoxins) through dialysis and haemofiltration membranes is of great importance. Using a quantitative turbidimetric method based on the LAL (limulus amoebocyte lysate) test LPS concentrations were measured in a closed in vitro system for 11 different dialysers and haemofilters. To assess the passage of endotoxin through the membrane, permeation was measured from the dialysate to the blood side as well as from the blood compartment to the dialysate side.

Endotoxins↗