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)

Rats were subjected to ligation of the common bile duct to provoke bile ductular proliferation and were studied at intervals from 1 day to 6 weeks. After perfusion fixation with glutaraldehyde, and ethanol dehydration, blocks of liver were frozen in liquid nitrogen, fractured, and returned to ethanol prior to critical point drying. Examination with the scanning electron microscope showed a remarkable proliferation of bile ductules and preductules in addition to canalicular dilation. The ductules were surrounded by a longitudinal array of collagen fibers. The luminal surfaces contained many microvilli and cable-like structures, some identifiable as cilia by transmission electron microscopy. The present techniques offer the possibility for a reevaluation of obstructive jaundice and cholestasis.
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PMID:Scanning electron microscopy of proliferating bile ductules. 116 Mar 51

Long-term parenteral nutrition hepatic-related impairment is commonly reported and diversely explained. However, with a low cyclic caloric intake (100% to 130% of basal metabolism calculated with the Harris-Benedict formula) consisting of two-thirds glucose, one-third lipid, and 0.20 to 0.25 g of nitrogen per kilogram per day, these complications were infrequent in a clinical practice of home long-term parenteral nutrition. Retrospectively, it was noticed that the switch from Intralipid 20% to Ivelip 20% at the same amount was followed within 2 months by four cases of jaundice in a population of four home long-term parenteral nutrition patients with short bowel disease. Hepatic disturbances were characterized by cytolysis and cholestasis and were reversible after switching from Ivelip 20% back to Intralipid 20%. Neither viral, nor biliary, nor septic etiologies were detected. The exact pathological mechanism remains unknown. The basal composition of both lipid emulsions seems to be identical: soy oil emulsion emulsified by egg phospholipids. However, some differences exist such as the size of particles, the presence of sodium oleate in Ivelip 20%, and the purification process of lecithin. These may explain the difference in hepatic tolerance during long-term parenteral nutrition.
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PMID:Hepatic cytolytic and cholestatic changes related to a change of lipid emulsions in four long-term parenteral nutrition patients with short bowel. 143 88

Total parenteral nutrition (TPN) has become a mainstay of modern neonatal care for the increasing population of premature infants who survive their initial pulmonary disease. As with other advances in neonatal therapy, hyperalimentation has associated complications and limitations, primary among them its toxicity to the liver. The basic pathologic lesion is bile cholestasis which is probably multifactorial in etiology. Amino acid solutions, excessive calorie-to-nitrogen ratios, and deficient trace elements and antioxidants have all been implicated in this process. Total parenteral nutrition-cholestasis can progress to portal fibrosis and irreversible cirrhosis if long-term hyperalimentation is required. Most at-risk for this iatrogenic condition are those premature infants less than 1500 g birth weight who are exposed to TPN for longer than two weeks. Enteral feedings providing as little as 10 percent of caloric intake are beneficial, and the prognosis for recovery is good once enteral feedings are established.
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PMID:Hyperalimentation associated hepatotoxicity in the newborn. 156 68

The most appropriate nutriment for total parenteral feeding (TPF) must be nutritionally efficient, safe and easy to use. Glucose is the most used carbohydrate as it has most of these qualities, as well as a high rate of metabolism by all tissues. It has not been clearly demonstrated that the administration of exogenous insulin with glucose improves nitrogen retention. Substitutes for glucose, such as fructose, maltose, galactose or polyols (xylitol, surbitol, glycerol) are not really superior to glucose itself. On the other hand, they have major side-effects. Therefore, they are not much used as energy substrates for TPF, at least not for long term TPF. Intravenous fat emulsions have taken an important place as a source of energy during TPF. Fat emulsions containing long chain triglycerides (LCT) supply essential fatty acids (EFA) (linolenic and linoleic acids), thus preventing EFA deficiency. The metabolism of fat emulsions is influenced by various factors: age, metabolic and nutritional status, the amount of glucose intake, insulin deficiency, sepsis, heparin therapy. Recently, medium chain triglycerides (MCT) have been proposed as an alternative energy source. The latter are cleared more rapidly from the blood, and are therefore less liable to be deposited in the liver and adipose tissue; they are also oxidized more quickly and more completely. MCT are safe to use at a rate of less than 0.12 g.kg-1.h-1 and with a MCT/LCT ratio less than 3 to 1. The simultaneous administration of glucose prevents an acceleration of ketogenesis. MCT/LCT emulsions are a safe and effective source of calories. It is important that those patients for whom such nutriment may be of particular interest should be identified. Fat emulsions associated with glucose seem to be more efficient in terms of nitrogen sparing effect than glucose alone. They also avoid the problems due to the infusion of large amounts of glucose (excessive carbon dioxide production, fatty infiltration of the liver), while there is no EFA deficiency. If the infusion of TPF nutriment must be continuous in intensive care patients, or during the postoperative period, cyclic nocturnal parenteral nutrition over a 12 or 16 hour period may be used in patients who are not in a catabolic state, or only mildly so. This is a safe and efficient method of nutritional support, which reduces the incidence rate of TPF-induced cholestasis.
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PMID:[Energy substrates in parenteral nutrition]. 178 8

The major biological functions of S-adenosyl-L-methionine (SAMe) include methylation of various molecules (transmethylation) and synthesis of cysteine (trans-sulphuration). A stable double salt of SAMe has been found to be effective in intrahepatic cholestasis. The mechanism of its therapeutic effect is not fully understood but presumably involves methylation of phospholipids. Methylation of plasma membrane lipids may affect membrane fluidity and viscosity, which modulate the activities of a number of membrane-associated enzymes, for example, the activity of enzymes involved in Na+/Ca++ exchange (e.g. sarcolemmal vesicles), Na+/K+ adenosine triphosphatase (ATPase) [e.g. hepatocyte plasma membranes], and Na+/H+ exchange (e.g. plasma membranes of colonic cells). Recently, patients with cirrhosis were shown to have an acquired metabolic block in the hepatic conversion of methionine to SAMe. These patients, when administered conventional elemental diets, develop abnormally low plasma concentrations of cysteine and choline, 2 nonessential nutrients present in low concentrations in most elemental diets. These low concentrations probably reflect systemic deficiencies attributable to reduced endogenous syntheses of cysteine and choline caused by limited availability of hepatic SAMe. Such cirrhotic patients are often in negative nitrogen balance and have abnormal hepatic functions, which are corrected by cysteine and choline supplements. Noncirrhotic patients on parenteral elemental diets also become deficient in cysteine and choline. Consequently, these patients may require SAMe as an essential nutrient to normalise their overall hepatic transmethylation and trans-sulphuration activities.
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PMID:Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease. 208 85

We sought to determine whether an excess in energy intake as total parenteral nutrition would result in liver biochemical and histological changes in the presence of a functional gastrointestinal tract. Three groups of rats were given amounts of total parenteral nutrition that provided either 25% (total parenteral nutrition-25), 100% (total parenteral nutrition-100), or 200% (total parenteral nutrition-200) of a rat's energy requirements. Rat chow and water were available ad libitum. Food intake decreased in proportion to the amount of total parenteral nutrition infused; it ceased with total parenteral nutrition-200. Liver glycogen and triglyceride concentrations were higher with high energy intake (total parenteral nutrition-100 and total parenteral nutrition-200), while total liver nitrogen concentrations remained unchanged. No cholestasis, inflammation, or fibrosis was seen histologically. Fatty vacuoles were increased with total parenteral nutrition (more so with total parenteral nutrition-200) but a prompt return to normal liver features was observed after cessation of total parenteral nutrition and the resumption of normal food intake.
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PMID:Liver biochemical and histological changes with graded amounts of total parenteral nutrition. 210 53

Patients who have an interruption of the small bowel with a high enterostomy usually need parenteral supply or reinfusion of chyme to maintain nutritional and electrolytic balances before restoring intestinal continuity. Ten patients (aged 28-76 years) with a terminal jejunostomy located within the first meter of jejunum were treated by infusion of an elemental diet into the distal small bowel (IEDDSB). In addition, five of these patients had an extensive small bowel resection. IEDDSB was started 32 days after operation and lasted 4 to 8 weeks. Mean daily caloric infusion was 1,732 +/- 666 kcal diluted in 2,860 +/- 808 ml; mean associated oral intake was 1,187 +/- 480 kcal/24 hr, and jejunal fecal losses averaged 3 kg per day. IEDDSB was well tolerated in 4 patients; 5 experienced transient abdominal pain or diarrhea; 1 developed severe and protracted diarrhea. Biological cholestasis was seen before IEDDSB and persisted in most patients; 1 patient developed biliary sludge. Through IEDDSB, nutritional status improved or remained satisfactory in 9 patients, and worsened in 1 patient with sepsis and a short lower intestine. Mean body weight, triceps skin fold, muscle circumference, serum albumin, serum transferrin did not change significantly. Digestive nitrogen balance performed in 6 patients showed a net absorption between 5 and 15 g/24 hr. Fluid and electrolyte balance was maintained in 9 patients and 1 received iterative intravenous saline. Digestive sodium balance showed a net absorption rate greater than 60 mmol/24 hr. in all patients, except the one who required intravenous supply. Postoperative recovery was uneventful in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Elemental feeding into the distal segment of a temporary small bowel]. 210 16

In 25 very low birth weight infants appropriate for gestational age the influences of different human milk (HM) preparations on weight gain, gross indices of nitrogen metabolism and energy balance were studied during the second month of postnatal life. HM was fortified either by HM-protein (HMP) or by an enzymatic meat protein hydrolysate (PH) to protein concentrations between 1.5 and 1.7 g/100 ml. The caloric densities of both HM preparations were similar between 62 and 68 kcal/100 ml. There were no differences in weight gain (MM + HMP: 18.6 +/- 3.4 g/kg/day; HM + PH: 16.5 +/- 4.1 g/kg/day), nitrogen retention (HM + HMP: 31.5 +/- 3.1 mmol/kg/day; HM + PH: 30.0 +/- 3.2 mmol/kg/day), and the preprandial estimated essential amino acid profiles between the both feeding groups. In contrast the serum concentrations of alpha-amino-nitrogen 60 minutes postprandially were elevated in the infants fed HM + PH in comparison to the infants fed HM + HMP. This high postprandial amino acid concentrations in serum in the group fed HM + PH were accompanied by increased bile acids concentrations in serum, higher renal amino acid excretion and increased fecal fat losses. The results suggest that due to the more rapid intestinal absorption of amino acids from PH than from HMP the concentrations of amino acids increase postprandially which results in a detectable increase of the newborn cholestasis in these infants. Nevertheless, the scale of these metabolic responses to feeding protein hydrolysates is small and without detectable influences on nitrogen retention or weight gain.
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PMID:Protein supplementation of human milk for the nutrition of VLBW-infants: human milk protein vs. meat protein hydrolysate. 221 90

Adverse drug reactions are more common in patients over sixty-five years of age. There is no significant change of absorption with aging but oxidations reactions are, usually, decreased. The most important change is in the renal elimination of drugs. The renal insufficiency related to the use of NSAIDs is prostaglandin dependent. It is characterized by a fall in urine output, body weight gain, rising of blood urea nitrogen, creatinine and, sometimes, potassium. This situation is usually rapidly reversible after discontinuation of the therapy but an acute renal failure may occur. Patients with atherosclerotic cardio-vascular disease and concurrent diuretic therapy have an increased risk of renal insufficiency. Liver damage induced by NSAIDs presents as an acute hepatitis with a greater or lesser degree of cholestasis. This picture is often indistinguishable from viral hepatitis and sometimes it may resemble chronic active hepatitis. Females with a concomitant impairment of renal function are specially at risk for liver damage and should be carefully followed on with a reduction of NSAIDs dosage.
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PMID:Renal and hepatic effects of NSAIDs in the elderly. 262 76

Low IGF-I levels are found in patients with chronic liver disease, but it is not known whether these reductions in IGF-I are secondary to hepatic dysfunction or to malnutrition. To determine whether malnutrition associated with hepatic dysfunction causes the decrease in these levels, serum and liver IGF-I concentrations and liver IGF-I mRNA content were compared in three groups of Sprague-Dawley rats: 15 rats underwent bile duct obstruction; 10 rats were sham-operated and pair-fed with operated rats to control for nutritional status; and 12 rats were sham-operated controls fed ad libitum. In addition, IGF-I peptide and mRNA were compared with food intake, crude nitrogen balance, total wt gain, tail length increase and leg muscle wt. All the parameters were lower in cholestatic and nutritionally deprived animals than in control animals (p less than 0.001). There was no difference in serum and hepatic IGF-I and liver IGF-I mRNA values between the 10 cholestatic and pair-fed animals, despite lower crude nitrogen balance, tail length gains, and leg muscle wt in the bile duct-obstructed animals. These studies suggest that in chronic bile duct obstruction, the low serum and hepatic IGF-I levels are primarily due to decreased food intake and appear unrelated to cholestatic liver disease itself. However, factors in addition to suboptimal nutrition and decreased IGF-I levels must also contribute to cholestasis-induced growth failure.
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PMID:Growth failure in cholestatic rats: the effect of malnutrition on insulin-like growth factor I. 281 90


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