Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent results regarding the pathophysiology of hyperlipoproteinemia in cholestasis are reported. The isolation of an abnormal lipoprotein (Lipoprotein-X; LP-X) from the plasma of cholestatic patients was achieved by a combination of various physico-chemical techniques. Most of the plasmacholesterol in these patients is transported in form of this abnormal lipoprotein which is very rich in phospholipids and unesterfied cholesterol. LP-X represents a vesicle with a mean diameter of 700 A. Albumin takes part as a structural protein of the particle. Besides albumin, which seems to be located in an internal water compartment or to be covered with lipids. Apo-C and Apo-D are present as surface proteins. The lack of Apo-B in LP-X, the major apoprotein of normal low density lipoproteins, seems to be the reason for a disturbed endogenous feedback mechanism of hepatic cholesterol synthesis, which is strongly increased in cholestasis. The high specificity and power of the LP-X test as clinical-chemical parameter to demonstrate or exclude cholestasis finds its explanation in our knowledge about the origin of this abnormal lipoprotein in cholestasis. LP-X is formed when a lipoprotein normally excreted with the bile refluxes into the plasma stream to convert into LP-X. This formation depends only on certain physico-chemical requirements and is independent of an energy-providing or enzymatically regulated process. The biological halflife of LP-X is similar to that of normal plasmalipoproteins. However, enzymes of postheparin plasma as well as the lecithin: cholesterol acyltransferase do not seem to play a major role in the catabolism of lipoprotein-X, but only change some of the physicochemical characteristics of this vesicle.
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PMID:[Studies on the structure and metabolism of lipoprotein-X (LP-X), the abnormal plasmalipoprotein in cholestasis (author's transl)]. 19 98

An investigation on the pathophysiological mechanisms underlying the hypoalbuminaemia and the hypercholesterolaemia of the pyometra syndrome in dogs was performed on 15 patients. The control material consisted of blood from 15 and urine from 6 healthy dogs. The presence of intrahepatic cholestasis in most of the dogs was indicated by an increase of serum alkaline phosphatases and phosphodiesterase I, and by the morphological demonstration of bile pigment retention in liver biopsy material. Serum cholesterol (total- and free-) was positively correlated with serum phospholipids, alkaline phosphatases and phosphodiesterase I, as regularly seen in cholestatic syndromes. Fibrinogen and alpha 2-globulins were increased in most patients. Albumin was inversely related to these parameters, and the main cause of the hypoalbuminaemia was probably the presence of an "acute phase reaction". The levels of coagulation factors in plasma were not lowered. Enzyme markers of hepatocellular injury (ALAT, OCT) were not increased, but on the contrary significantly lowered. The possible presence of enzyme inhibitors as the cause of the decrease of ALAT and OCT is discussed.
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PMID:Pyometra in the dog--a pathophysiological investigation. V. The presence of intrahepatic cholestasis and an "acute phase reaction.". 743 16

Artificial liver support aims to prolong survival time of patients with liver failure by detoxification. Albumin as a molecular adsorbent in dialysis solution is capable of attracting even tightly albumin-bound toxins from blood into the dialysate if a specific dialysis membrane is used and if the albumin's binding sites are on-line-purified by a sorbent/dialysis-based recycling system (i.e., molecular adsorbents recycling system, or MARS). The MARS technology has been shown to remove water-soluble and albumin-bound toxins and to provide renal support in case of renal failure. Fourteen centers have reported that MARS treatment improved mental status of patients with liver failure and hepatic encephalopathy. In treating liver failure and cholestasis, MARS was associated with hemodynamic stabilization, improvement of hepatic and kidney function, and disappearance of pruritus. In hepatic failure and hepatorenal syndrome, a prospective, randomized, controlled trial of MARS treatment was able to prolong survival time significantly. MARS has been used in 26 patients with acute liver failure or primary graft dysfunction. Nineteen centers reporting on 103 patients have shown that MARS treatment is safe, easy to handle, feasible, and effective.
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PMID:The molecular adsorbents recycling system as a liver support system based on albumin dialysis: a summary of preclinical investigations, prospective, randomized, controlled clinical trial, and clinical experience from 19 centers. 1187 37

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of MARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.
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PMID:Albumin liver dialysis as pregnancy-saving procedure in cholestatic liver disease and intractable pruritus. 1903 Feb 15

A primary nonfunctioning graft, the complication that develops in less than 5% of patients within the first 24-48 hours after hepatic transplantation, is responsible for high death rates in recipients. Its manifestations are an extremely grave clinical condition, hypotension, unconsciousness, progressive signs of hepatocytic insufficiency with increases in bilirubin levels and serum transaminase activities, addition of renal failure, and development of multiple organ dysfunctions. Eight patients underwent a total of 17 albumin dialysis sessions (1 to 5; mean 2.1). Each session lasted 6 hours. Albumin dialysis caused a significant reduction in the levels of serum bilirubin and its conjugated fraction, by an average of 24.7 +/- 15.1% per session. The activity of the serum enzymes of cytolysis and cholestasis significantly decreased with the parameters being stabilized within 7 days. Stabilization of hemodynamic parameters and better neurological status were noted in patients during treatment. The survival rate was 75% on days 7, 20, and 30. Hepatic retransplantation was made in 2 patients; 4 were discharged home and 2 died from multiple organ dysfunctions. Albumin dialysis used in patients with graft dysfunction provides a possibility of maintaining the patient in the critical period of searching for a donor's organ or regenerating the graft's function.
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PMID:[Albumin dialysis (MARS therapy) in patients with hepatic graft dysfunction]. 1922 98

Albumin dialysis using the molecular adsorbent recirculating system (MARS) is a new therapeutic approach for liver diseases. To gain insight into the mechanisms involved in albumin dialysis, we analyzed the peptides and proteins absorbed into the MARS strong anion exchange (SAX) cartridges as a result of the treatment of patients with cholestasis and resistant pruritus. Proteins extracted from the SAX MARS cartridges after patient treatment were digested with two enzymes. The resulting peptides were analyzed by multidimensional liquid chromatography coupled to tandem mass spectrometry. We identified over 1,500 peptide sequences corresponding to 144 proteins. In addition to the proteins that are present in control albumin-derived samples, this collection includes 60 proteins that were specific to samples obtained after patient treatment. Five of these proteins (neutrophil defensin 1 [HNP-1], secreted Ly-6/uPAR-related protein 1 [SLURP1], serum amyloid A, fibrinogen alpha chain and pancreatic prohormone) were confirmed to be removed by the dialysis procedure using targeted selected-reaction monitoring MS/MS. Furthermore, capture of HNP-1 and SLURP1 was also validated by Western blot. Interestingly, further analyses of SLURP1 in serum indicated that this protein was 3-fold higher in cholestatic patients than in controls. Proteins captured by MARS share certain structural and biological characteristics, and some of them have important biological functions. Therefore, their removal could be related either to therapeutic or possible adverse effects associated with albumin dialysis.
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PMID:Proteomic analysis of polypeptides captured from blood during extracorporeal albumin dialysis in patients with cholestasis and resistant pruritus. 2177 39