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Biomedical subjects

K Haag

Publications and source records attributed to K Haag.

At least 55 records · Page 3Linked to original sources

Synaptic membrane complex carbohydrates in experimental hepatic encephalopathy.

To evaluate further the status of synaptic plasma membranes (SPMs) in the brain in the syndrome of hepatic encephalopathy (HE) lipid- and protein-bound sialic acid and ganglioside and protein composition were investigated in SPMs from the brains of six rabbits with galactosamine-induced fulminant hepatic failure and five normal rabbits. HE was associated with no appreciable changes in the chromatographic pattern of gangliosides or the concentration of protein-bound sialic acid, but the syndrome was associated with a 20% increase in lipid-bound sialic acid and, as assessed electrophoretically, an increase in the concentration of a protein with a molecular weight of about 70 kDa. Thus, changes in the composition of complex carbohydrates and protein in SPMs occur in a model of HE. The findings raise the possibility that nonhumoral factors, such as increased sialylation of glycolipids, contribute to the generation of abnormal neurotransmission in HE.

Animals↗

Determination of short-circuit current in small tubular structures via cable analysis.

Use of cable analysis is a time-consuming maneuver. On the other hand, the advantage of the cable method consists in obtaining the Isc and Rm related to unit area without the explicit measurement of inside radius r of the tubular structure. Obviously, application of the clamping technique requires, in addition, the determination of the surface area. In summary, for small tubular structures, such as the salivary ducts of rats and rabbits, and for human experiments, cable analysis is the method of choice for the Isc determination in vivo as well as in vitro. For larger tubular structures such as the rat colon the Isc should be determined in vivo by the clamping technique described above, whereas the in vitro measurements should be done in an Ussing-type chamber. In the intermediate range of size both in vivo techniques should be applied, in which case one method may serve as a check of the other.

Animals↗

Sulfated bile acids inhibit Na(+)-H+ antiport in human kidney brush-border membrane vesicles.

Patients with obstructive jaundice are at a high risk for acute renal failure after surgery. Direct toxic membrane effects of bile acids or bilirubin have been discussed as possible causes. Therefore, we investigated the influence of bile acids and conjugated bilirubin on Na(+)-H+ antiport and ion permeabilities in brush-border membrane vesicles isolated from the human kidney. Brush-border membrane vesicles were prepared by Mg2+ precipitation. These were highly purified as estimated from the 14-fold enrichment in the specific activity of alanine aminopeptidase. The pH-sensitive dye acridine orange was used to study the properties of proton uptake under different conditions. The brush-border membrane vesicles from human kidney cortex exhibited Na+ and K+ conductances, which were small compared with H+ conductance. Furthermore, these membranes possess an Na(+)-H+ antiporter that is sensitive to amiloride. Various bile acids (30 microM) had no significant effect on Na(+)-H+ antiport. However, the addition of sulfated bile acids resulted in a significant inhibition (greater than 50%) of the Na(+)-H+ antiporter. A nonspecific effect of sulfated bile acids on the vesicles was excluded by the use of ionophores to determine vesicle integrity and to estimate the various ion conductances. Therefore specific inhibition of the human renal Na(+)-H+ antiporter by sulfated bile acids occurs. This could result in an impaired cellular pH regulation and might play a role in postoperative acute renal failure in patients with obstructive jaundice.

Acridine Orange↗

[Hemodynamic consequences of portal decompression: which is the optimal shunt?].

Increased sinusoidal resistance in cirrhosis results in a decrease of the portal and a compensatory increase of the arterial blood supply to the liver. With increasing vascular resistance and development of extrahepatic collaterals stagnation and even reversion of the portal blood flow may occur. In the latter condition, the arterial blood leaves the liver through two routes: 1) through the sinusoids and the hepatic veins, and 2) through the portal vein. Experimental and clinical studies revealed that the arterio-portal pathway is metabolically inferior to the regular arterio-hepatic-venous pathway. This suggests a decrease in liver function with an increased incidence of hepatic encephalopathy (HE) in patients with reversed portal blood flow. Based on these findings, surgical shunts may be classified according to their effect on the arterial liver perfusion. The end-to-side shunt and the distal splenorenal shunt (DSRS) do not cause diversion of the arterial liver perfusion. In contrast, side-to-side shunts, with the portal vein available as an outflow tract, consistently lead to diversion of the arterial blood supply resulting in reversed portal blood flow. Thus, side-to-side shunts are supposed to have an increased incidence of HE due to decreased liver function. This hypothesis is supported by 7 controlled and randomized studies which reveal comparable results of end-to-side shunts and DSRS but significant disadvantages of side-to-side shunts compared to DSRS.

Hemodynamics↗

Correlation of caffeine elimination and Child's classification in liver cirrhosis.

Apparent pharmacokinetic parameters of caffeine elimination from the circulation were determined in 27 patients with histologically confirmed liver cirrhosis, 8 patients with miscellaneous liver disease, and 8 patients with other than liver disease. The usefullness of this quantitative test to assess the severity of liver cirrhosis was compared to the Child-Turcotte or Child-Pugh classification score as well as to the galactose elimination capacity of these patients. Using reversed-phase high pressure liquid chromatography caffeine, paraxanthine, theophylline, and theobromine were analysed in blood plasma collected before and after an oral dose of caffeine. Compared to apparent caffeine pharmacokinetics in patients with normal livers or miscellaneous liver disease, cirrhosis was characterized by a statistically significant reduction in apparent caffeine clearance and prolongation in half-life. The reduced apparent plasma disappearance rate of caffeine in cirrhotics was related to the retarded formation of paraxanthine which was the main metabolite of caffeine in blood plasma both in the absence or presence of liver disease. The apparent caffeine clearance in cirrhosis decreased with increasing Child-Turcotte classification score: Child's class A patients differed significantly from Child's class B or Child's class C patients, whereas the difference between Child's class B and C patients did not reach statistical significance (Wilcoxon's rank test). In addition there was a strong correlation between the Child-Pugh classification score and apparent caffeine clearance (P less than 0.001). However, no correlation existed between Child's classification and galactose elimination capacity. Our data emphasize the value of the Child-Turcotte or Child-Pugh classification in assessing the severity of liver cirrhosis in a simpler and less time-consuming way than using quantitative liver function tests.

Administration, Oral↗

Modelling of colonic Cl- and K+ transport under resting and secreting conditions.

Transport of electrolytes, particularly of Cl- and K+, by the rat proximal colon was studied in vivo under conditions of high and low K+ diet and in the presence of transport inhibitors and secretagogues. The electrical parameters, PD, Isc, Rm, were monitored by direct clamping and via cable analysis. The present work reinforces own earlier work and that of others that - under control conditions - absorption of Na+ and Cl- is mainly electrically neutral. Low K+ diet reduced absorption of Na+ and Cl-, as well as secretion of K+, and increased HCO3- absorption. High K+ predominantly increased K+ secretion and reduced HCO3- absorption, these diet-induced changes being electrically neutral. Secretagogues such as PGE1 and theophylline reduced net absorption of Na+ and Cl-, increased the Isc and lowered the Rm. These effects could be reversed by the antidiarrheal drugs, loperamide and somatostatin, except the increase of K+ secretion, and reversed HCO3- transport absorption to secretion. A model consisting of absorptive columnar cells and secreting crypt cells is presented which encompasses the known and supposed aspects of colonic ion transport.

Alprostadil↗

Ion transport in rat proximal colon in vivo.

Active Na+ absorption by the rat proximal colon in vivo is for the most part electrically silent. The rheogenic Na+ flux makes up only 8%. To elucidate the underlying transport pathways, the following experimental approaches were used: ion substitution experiments such as choline for Na+, cyclamate for Cl-, variation of luminal pH; administration of known inhibitors; and determination of changes in luminal CO2 tension and pH. The transcolonic ion fluxes as well as the electrical parameters potential difference, specific electrical resistance, and short-circuit current were monitored. Na+ transport was drastically reduced in the absence of luminal Cl-, and vice versa Cl- absorption was blocked at zero Na+. NaCl absorption was blocked by amiloride (10(-3) M) and 4-acetamido-4'-isothiocyanostilbene-2, 2'-disulfonic acid and was lowered by acetazolamide. Colonic NaCl absorption was not influenced by luminal furosemide. Na+ absorption increased with alkalinization of the luminal fluid. Tris instead of HCO-3 buffer at constant pH favored Cl- uptake. The results may easily be explained by the operation of a Na+-H+ antiport functionally coupled to a Cl(-)-HCO-3 antiport. These transport processes are supposed to be present in the columnar cells of the colonic epithelium. There is good evidence for the association of K+ secretion with rheogenic Cl- secretion by the crypt cells.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

Temporal gait monitoring: a new device.

A new device that provides continuous recording of gait and gait events is presented. It can be used with motor point electromyography to perform walking electromyography, an electrogoniometer to continuously record joint position, or other measuring devices to record events or activities related to phase of gait. The major advantages of this system as compared with available systems are ease of use, decreased patient encumbrance, potential for portability, potential for digitizing the signal for minicomputer compatibility, and greatly reduced expense.

Adult↗

Determination of rheogenic ion transport in rat proximal colon in vivo.

A direct clamping technique is demonstrated, which allows monitoring of rapid changes of the short-circuit current (Isc) and the specific transepithelial resistance (Rm) as well as measurement of ion fluxes under short-circuit conditions in vivo. Due to the cylindrical symmetry of the colon the intraluminal electrode was devised as a centrally fixed silver rod, by which radial current injection was achieved. The geometrical arrangement of the electrodes guaranteed zero potential difference (PD) along the whole axis of the colon segment. The Isc was determined to 3.3 +/- 0.7 mueq h-1 cm-2 and Rm equal to 121 +/- 5 omega cm2. These data obtained by direct short-circuiting agree well with our earlier Rm and Isc data based on cable analysis, where the Isc was calculated from the open-circuit PD and Rm. This is considered as evidence for the reliability of the two independent in vivo techniques. Their validity was confirmed by the expected effects of drugs acting on rheogenic ion transport. Both the indirect (via Rm) as well as the direct Isc determination may be used alternatively as required; one may serve to match the other. For larger tubular structures like the rat colon the direct clamping should be preferred as the standard procedure for the Isc determination in vivo.

Alprostadil↗

Evidence for mitochondrial origin of the HCO3(-)-ATPase in brush border membranes of rat proximal tubules.

High HCO3(-)-ATPase activity is known to exist in mitochondria of renal tubular cells. In brush border membrane (BBM) preparations of proximal tubules such an anion-stimulated enzyme was also found. However, these preparations always contained mitochondrial markers. The putative localization and the role of this ATPase in BBM is still controversial. Some authors consider the HCO3(-)-ATPase in the BBM to be a mitochondrial contamination; others attribute to this ATPase a key role in H+ transport in the proximal tubule. To reinvestigate this problem, BBMs from rat kidney cortex were isolated by a simple, rapid (1.5-h) Ca2+-precipitation method, yielding a BBM fraction enriched 12.4-fold with respect to the marker enzyme leucine aminopeptidase (LAP). There was no basolateral Na+-K+-ATPase and no mitochondrial succinate dehydrogenase detectable. Cytochrome c oxidase was drastically reduced to 7 +/- 1% of that observed in the homogenate (TH). The activity of HCO3(-)-ATPase in the BBM fraction was 19 +/- 4 IU/g protein, i.e., 27% that of the homogenate. As sonication of the TH exclusively increases the activity of HCO3(-)-ATPase, its relative activity was 7.5% and thus equal to that of the mitochondrial marker. In many BBM preparations no HCO3(-)-ATPase was detectable. In those BBM preparations in which traces of HCO3(-)-ATPase were found, this activity coincided with that of cytochrome c oxidase in the respective preparation. There was a constant activity ratio of cytochrome c oxidase/HCO3(-)-ATPase in the TH, BBM, and pellet 1. The activity of HCO3(-)-ATPase in BBM did not depend on the activity of LAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗