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R W Grunewald

Publications and source records attributed to R W Grunewald.

14 recordsLinked to original sources
PubMed1992

Blood rheology after LDL apheresis using dextran sulfate cellulose absorption--a case report.

The authors describe a thirty-eight-year-old woman with familial hypercholesterolemia treated by dextran sulfate cellulose adsorption apheresis. This technique and the selective extracorporeal LDL cholesterol elimination by immunoabsorption or heparin-induced precipitation not only dramatically decrease blood lipids but also result in a marked improvement in the rheologic profile. It is suggested that the amelioration of blood rheology by LDL apheresis may represent the cause for the early clinical improvement felt by most patients with severe coronary heart disease and hypercholesterolemia.

Adsorption↗
PubMed1992

[LDL cholesterol apheresis by adsorption to dextran sulfate].

Extracorporeal LDL cholesterol elimination may be the sole successful treatment in familial hypercholesterolemia. By treatment of 41 plasma both total cholesterol and LDL cholesterol were lowered by 69 +/- 1% and 78 +/- 1%, respectively. HDL cholesterol was decreased by 24 +/- 3%. This could be explained both by hemodilution (hematocrit was decreased by 9.3 +/- 2.8%) and unspecific adsorption of various plasma proteins (-15.3 +/- 3.7 g/l, i.e. -22 +/- 4%). Protein electrophoresis showed different affinities of the protein fractions. These data suggest that LDL apheresis by dextran sulfate is an effective method for the elimination of LDL cholesterol. However, other proteins besides apolipoprotein B are adsorbed to dextran sulfate.

Adsorption↗
PubMed1991

Clearance of osteocalcin in adults with end-stage renal disease undergoing CAPD.

Osteocalcin (OC) is a bone-specific protein whose blood concentration is a specific and sensitive marker of bone turnover. In adults undergoing continuous ambulatory peritoneal dialysis (CAPD), mean serum osteocalcin levels (S-OC) are lower than in similar patients on hemodialysis. We therefore measured the serum (S) and dialysate (D) levels of OC, estimated the peritoneal clearance (Cp) and mass transfer (MT) of OC and evaluated the relationship between S-OC levels and other serum biochemical parameters of bone metabolisms. Fourteen adult patients on CAPD were studied with a mean age of 46.3 +/- 13 years and a mean dialytic age on CAPD of 17.4 +/- 9.6 months. OC concentrations in (S) and (D) were 60.8 +/- 55.5 micrograms/l (normal range: 4.3-12.4 micrograms/l) and 6.9 +/- 6.2 micrograms/l, respectively. The Cp of OC was 1.08 +/- 0.3 ml/min and the MT of OC over 4-h dialysis exchange periods was 14.5 +/- 12.3 micrograms when using a dialysis solution containing 2.27% glucose. S-OC was significantly correlated with serum levels of alkaline phosphatase (r = 0.80), intact PTH (r = 0.82) and the MT of OC (r = 0.94). No significant correlations were found with serum levels of total calcium, phosphate, creatinine, total protein and dialytic age. These results suggest that the OC level in serum is influenced by both bone turnover and peritoneal clearance. Therefore, altered serum levels of OC should be interpreted always together with the peritoneal mass transfer of OC. Taking this into account, OC and intact PTH may be of value as markers of increased bone turnover secondary to renal osteodystrophy in CAPD.

Adult↗
PubMed1990

[Study of kidney function using isolated cells].

After summarizing the progress which has been made with regard to the isolation and characterization of homogeneous cell populations from the kidney, a brief survey of current techniques available for the analysis of intracellular parameters is given. Special emphasis is thereby placed on the use of electron probe X-ray microanalysis to determine intracellular elements and on "in vivo" nuclear magnetic resonance to define metabolic pathways in isolated cells. These methods have been applied to study ion and substrate fluxes in isolated collecting duct cells and the response of these cells to changes in osmolality of the extracellular medium. This response involves initially fast water movements accompanied by changes in intracellular sodium and chloride but not potassium concentration. Longterm adaptation is achieved by the adjustment of the intracellular concentration of "organic osmolytes" such as sorbitol, myoinositol, glycerophosphorylcholine, and betaine through changes in the rate of efflux of these metabolites from the cell. In the last section the effect of experimentally induced diabetes mellitus on the osmoregulation in isolated collecting ducts is described.

Animals↗
PubMed1989

Pathways for the synthesis of sorbitol from 13C-labeled hexoses, pentose, and glycerol in renal papillary tissue.

Suspensions of rabbit renal papillary tissue were incubated with D-[6-13C]glucose, D-[1-13C]fructose, D-[1-13C]ribose, and [2-13C]glycerol. The perchloric acid extracts of the above incubations were investigated with 13C NMR spectroscopy. All 13C-labeled substrates give rise to 13C-labeled D-sorbitol. D-[6-13C]Glucose and D-[1-13C]fructose are converted directly into D-sorbitol via the aldose reductase and sorbitol dehydrogenase pathway, respectively, whereas D-[1-13C]ribose and [2-13C]glycerol give rise to labeling of the D-glyceraldehyde pool which on its turn causes a labeling of D-sorbitol. Label exchanges observed from incubations with glycerol and D-ribose indicate that the pentose shunt plays a role in this synthesis of D-sorbitol.

Animals↗
PubMed1989

Intracellular sorbitol content in isolated rat inner medullary collecting duct cells. Regulation by extracellular osmolarity.

In order to study the mechanisms involved in the regulation of renal inner medullary sorbitol content, collecting duct cells were isolated from rat inner medulla and the effect of extracellular osmolarity on sorbitol synthesis and sorbitol content was investigated. Cells isolated at 300 mosmol/l and incubated up to 24 h as primary cultures in 300 mosmol/l media or in media made 600 mosmol/l by the addition of 150 mM NaCl showed no difference in total synthesis. Intracellular sorbitol content was, however, 2.3-fold higher in the cells kept in the higher osmotic medium. Cells isolated at 600 mosmol/l released sorbitol about 8 times faster when transferred into hypoosmotic medium (300 mosmol/l) than when transferred into isoosmotic (600 mosmol/l) media. Cells exposed to hyperosmotic media (900 mosmol/l with NaCl) maintained a higher intracellular sorbitol content than cells incubated in isoosmotic media. Changes of intracellular sorbitol content could not be attributed entirely to cell lysis--as demonstrated by determination of cellular content of lactate and lactate dehydrogenase. The alteration in sorbitol membrane permeability was reversible and was only observed when poorly permeable solutes (such as NaCl and sucrose) were used for the experiments, changes in urea elicited no effect. It is proposed that rapid changes in membrane permeability to sorbitol play an important role in the adjustment of intracellular sorbitol concentration in inner medullary collecting duct cells to changes in extracellular osmolarity.

Animals↗
PubMed1989

Sorbitol metabolism in inner medullary collecting duct cells of diabetic rats.

Intracellular accumulation of sorbitol, generated from D-glucose via the aldose reductase pathway, is thought to play an important role in diabetic complications such as lens cataracts and neuropathy. In order to elucidate the effect of diabetes on the renal inner medulla, another sorbitol-rich tissue, male Wistar rats were treated with a single dose of streptozotocin (60 mg/kg body weight, i.p.). Six weeks later total inner medullary tissue (IM) or isolated inner medullary collecting duct (IMCD) cells were prepared. In diabetic IM tissue, sorbitol content was 1.8-fold higher than in control IM tissue (134 +/- 17 vs. 74 +/- 22 mumol/g tissue protein). Sorbitol production in both normal and diabetic IMCD cells was strongly dependent on extracellular D-glucose concentration. In normal cells, for example, sorbitol production was 90 +/- 9 mumol sorbitol/g protein x h at 45 mM D-glucose compared to 13 +/- 1 mumol/g protein x h at 5 mM. At identical D-glucose concentrations sorbitol synthesis in diabetic IMCD cells was, however, always significantly higher than in control cells (122% of control at 15 mM and 126% of control at 45 mM). In addition, aldose reductase activity in diabetic IM was found to be augmented. The maximal velocity was 4.2 times higher (97 +/- 22 U/g protein vs. 23 +/- 7 U/g protein) while the Km of the enzyme remained unchanged. Membrane permeability for sorbitol or the response to changes in extracellular osmolarity was not significantly different in diabetic IMCD cells and normal cells with correspondingly high intracellular sorbitol concentrations. Similarly the kinetic parameters of D-glucose uptake were not altered by streptozotocin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1989

A Na-K-Cl cotransporter in isolated rat papillary collecting duct cells.

Lactate production and ion fluxes were measured in isolated rat papillary collecting duct cells (PCD) to gain further insight into the transport properties of the papillary collecting duct. Lactate production was found to be inhibited by bumetanide in a dose-dependent manner, a maximum inhibition of 22% was obtained at 10(-4) M bumetanide and an apparent Ki of 10(-8) M was determined. Bumetanide inhibition of lactate production was dependent on the presence of sodium and chloride. Chloride removal inhibited lactate production also by 20%. Bumetanide (10(-4) M) inhibited by 35% sodium uptake into PCD cells exposed to 10 mM ouabain and chloride uptake into ion depleted PCD cells by 40%. In addition, this bumetanide-sensitive chloride uptake was dependent on the presence of sodium and potassium in the incubation medium. Furthermore, 86Rb uptake into these cells was significantly reduced in the presence of 10(-4) M bumetanide. These data provide evidence for the operation of a Na-K-Cl cotransport system in rat papillary collecting duct cells. This transport system might be involved in active chloride transport in the papillary collecting duct and/or volume regulation of the PCD cells.

Animals↗
PubMed1988

Pathways for organic osmolyte synthesis in rabbit renal papillary tissue, a metabolic study using 13C-labeled substrates.

Renal papillary collecting duct cells have been postulated to adapt their intracellular osmolality to the large changes in interstitial osmolality by changing their content of 'non-perturbing' organic osmolytes such as sorbitol and myo-inositol. 13C-NMR was used in this study to elucidate the metabolic pathways leading to a synthesis of those compounds. Incubation of rabbit renal papillary tissue with [1-13C]glucose showed label scrambling mainly into sorbitol (C-1) and lactate (C-3). This result confirms activity of aldose reductase and glycolytic enzymes in renal papillary cells. Using [3-13C]alanine or [2-13C]pyruvate as carbon source, 13C-labeling of sorbitol and myo-inositol was observed, indicating that renal papillary tissue possesses, in addition, gluconeogenic activity. The latter assumption is supported by the result that in enzyme assays rabbit kidney papilla and isolated rat kidney papillary collecting duct cells show significant fructose-1,6-bisphosphatase activity.

Alanine↗
PubMed1988

[Transport mechanisms and metabolic processes in isolated cells of the collecting tubule of the kidney papilla].

Taking into account recent results obtained with isolated papillary collecting duct cells the metabolic pathways and membrane transport systems of collecting duct cells are reviewed. The plasma membranes contain a luminal proton AT-Pase and a contraluminal Cl-/HCO3- exchanger which are involved in proton secretion; a luminal sodium channel and a contraluminal Na+/K+-AT-Pase for sodium reabsorption; a K+ channel for potassium secretion, and a Na+/K+/Cl- cotransport system for chloride transport and/or volume regulation. The plasma membranes also possess transport systems for organic substrates and organic osmolytes. D-glucose, the main substrate of the papillary collecting duct is taken up into the cell by a sodium-independent D-glucose transport system with a Km of 1.2 mM. The plasma membrane also contains mechanisms which mediate sorbitol release into the medium. This mechanism is stimulated when cells are exposed to media with a low osmolality and inhibited when cells are exposed to media with a high osmolality. D-glucose is used as metabolic substrate in anaerobic and aerobic glycolysis and as precursor for sorbitol synthesis via the aldose reductase, which is highly enriched in papillary collecting duct cells. The cells also show gluconeogenic activity as evidenced by incorporation of labeled carbon from L-alanine into glycerol, sorbitol, and myo-inositol. Accordingly, the cells show fructose-1,6-biphosphatase activity. Sorbitol synthesis in contrast to sorbitol permeability is not affected by osmolarity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Sugar transport in isolated rat kidney papillary collecting duct cells.

D-Glucose is an important substrate of energy metabolism and osmolyte synthesis in the renal papillary collecting duct. In order to characterize the cellular entry of D-glucose in this tubular segment, collecting duct cells were isolated from rat kidney papilla and the rate of D-glucose uptake was measured indirectly by monitoring the D-glucose-dependent O2 uptake in the presence of the uncoupler CCCP. D-Glucose uptake was found to be sodium-independent and not sensitive to phlorizin even at a concentration of 10(-3) M. Uptake was, however, completely inhibited by 10(-5) M cytochalasin B and 10(-4) M phloretin. The apparent Ki for cytochalasin B was 1.5 x 10(-6) M and for phloretin 2.0 x 10(-5) M. Studies on the substrate specificity revealed that at 1 mM D-mannose is taken up and metabolized to the same extent as D-glucose. A 50-fold higher concentration of 2-deoxy-D-glucose and 2-amino-2-deoxy-D-glucose inhibited D-glucose uptake completely whereas alpha-methyl-D-glucoside, D-allose, and D-galactose were without effect. Under conditions where D-glucose utilization was maximally stimulated an apparent Km of 1.2 mM and a Vmax of 1 mmol D-glucose/g protein.hour was found for D-glucose uptake. These results indicate that the D-glucose uptake into papillary collecting duct cells is probably mediated by a transport system similar to the one found in basal-lateral membranes of polarized renal, intestinal, and liver cells as well as in nonpolarized fat cells and erythrocytes.

Animals↗