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Biomedical subjects

J Stange

Publications and source records attributed to J Stange.

15 recordsLinked to original sources
PubMed1996

Rapid HPLC assay for verapamil and its metabolites: use for application to in vitro studies.

An improved method using isocratic reversed phase HPLC is presented for the extraction and rapid determination of verapamil and its main metabolites in microsomal preparations and cell culture media. Possibilities for using the method to estimate cytochrome P450 enzymes in microsomal test systems and hepatocyte cultures are described. The studies show that primary hepatocyte cultures are suitable for studying the metabolism and interactions of pharmaceuticals in vitro and could be superior to microsomal systems in many cases.

Biotransformation↗
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

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↗
PubMed1990

[An improved method for the microencapsulation of liver microsomes for use in extracorporeal detoxication].

Rat liver microsomes were microencapsulated in a pure aqueous medium by means of a new technique. The wall of the microcapsules consists of a semipermeable simplex membrane which is stabilized mainly by electrostatic interactions between a polymeric polyanion (sodium cellulose sulphate) and a polymeric polycation (polydimethyldiallylammonium chloride). The metabolic as well as the mechanic parameters of the microcapsules could be markedly improved by separating the metabolic (liver microsomes) from the membrane component (sodium cellulose sulphate) in such a way that two distinct compartments are formed during the preparation of the microcapsules.

Animals↗
PubMed1989

["Elastic osteosynthesis" with autocompression plates of carbon fiber reinforced thermoplastic material].

The problem of atrophic bone that occurs in osteosynthesis employing rigid plates is first depicted. Attempts at fabricating "simirigid" plates, which, however, have so far failed to gain any practical importance are then discussed. The reason for this seems to be that made of duroplastics cannot be molded during the operation and the thermoplastics do not have sufficient strength. The production of semirigid plates made of thermoplastic Polyethersulfon (PES), reinforced with 20% short carbon fibres, results in plates which are made moldable by heating in a small oven, white retaining sufficient static strength, although only limited fatigue strength. Biomechanical examinations revealed that with appropriate dimensioning of the plates, "elastic osteosynthesis" results in less loss of mechanical function of the stabilized bones, so that less atrophy of the bone may be expected. During more pronounced exercise loading, a reversible "springiness" of the fracture results, which might stimulate callus formation and improved stability.

Bone Plates↗
PubMed1978

Disruptive behavior: a dietary approach.

The effect of particular foods on levels of hyperactivity, uncontrolled laughter, and disruptive behaviors was studied in an 8-year-old autistic boy. The floor of the child's room was taped off into six equal-sized rectangles to measure general activity level. Frequency data were recorded on screaming, biting, scratching, and object throwing. A time-sample technique was used to record data on laughing. Data were gathered during four phases. During an initial 4-day period the child was fed a normal American diet. A 6-day fasting period followed, during which time only spring water was allowed. The third phase lasted 18 days and involved the presentation of individual foods. During the final phase of the study the child was given only foods that had not provoked a reaction in the third phase. Results showed that foods such as wheat, corn, tomatoes, sugar, mushrooms, and dairy products were instrumental in producing behavioral disorders with this child.

Autistic Disorder↗
PubMedDate not supplied

Primary or established liver cells for a hybrid liver? Comparison of metabolic features.

It is currently in discussion whether or not established liver cell lines can be used for an extracorporeal liver assist device. Thus, metabolic features of primary hepatocytes, immortalized hepatocytes, and hepatoma cells were compared. The ability of these cells to process toxic blood of patients with hepatic failure was investigated by testing their viability in toxin enriched medium that was obtained by toxin separation from patients' blood via a molecular adsorbents recirculating system (MARS). In addition, glucose metabolism, urea synthesis, P450 dependent verapamil metabolism using high performance liquid chromatography, and interleukin-6 induced "acute phase" reaction by sulfodesoxysalicylic acid-polyacrylamide gel electrophoresis detected changes of albumin synthesis were determined in primary hepatocytes and in established liver cells. The viability of hepatoma cells after contact with the toxic compounds coming from the patients' blood was significantly decreased in comparison to that of immortalized hepatocytes and primary hepatocytes. Immortalized hepatocytes and hepatoma cells showed a significantly higher consumption of glucose associated with a significantly higher lactate synthesis. A basic urea synthesis rate could be measured in immortalized hepatocytes and hepatoma cells, but it was significantly lower than that of primary cells. P450 with its subenzyme CYP2C was inducible only in primary hepatocytes and in immortalized cells, but in the latter the enzymatic activity was lower than that of primary cells. The incubation with acute phase mediators resulted in a decrease of albumin synthesis in primary hepatocytes and in hepatoma cells, but it increased the albumin synthesis in immortalized hepatocytes. Summarizing these data, partially beneficial effects can be assumed if established cells are used in an extracorporeal liver assist device. These might include synthesis of some compounds and basic metabolic activities, such as urea synthesis. However, established liver cells showed clearly altered metabolic characteristics. The sufficient removal of toxic compounds requires additional strategies for detoxification by primary hepatocytes in sufficient amounts.

Acute-Phase Reaction↗
PubMedDate not supplied

A new procedure for the removal of protein bound drugs and toxins.

To extend the applicability of dialysis to the removal of albumin bound toxins, a new dialysis procedure was developed. A double sided albumin impregnated high-flux polysulfon dialyzer was used together with a closed loop dialysate compartment with an albumin containing dialysate solution, that was purified on line in a three step process with a charcoal and resin adsorbent, and another dialyzer for a normal dialysis or filtration of the albumin containing dialysate that was then recycled to the albumin impregnated dialyzer. The system effectively removed strongly albumin bound toxins like unconjugated bilirubin or free fatty acids from plasma and blood in vitro and in vivo and therefore could be considered a possible therapeutic means for the treatment of acute liver failure or acute and chronic intoxications with albumin bound toxins, e.g., in drug overdose or chronic renal failure.

Adult↗