Search PubMed⌕ Search

Biomedical subjects

C C Roy

Publications and source records attributed to C C Roy.

At least 55 records · Page 3Linked to original sources
PubMed1989

Relationship of decreased hepatic lipase activity and lipoprotein abnormalities to essential fatty acid deficiency in cystic fibrosis patients.

Polyunsaturated fatty acids are known to affect plasma lipids and lipoproteins but there is no information on the effect of essential fatty acid (EFA) deficiency on lipoprotein composition. The purpose of this study was to characterize lipoproteins from 17 cystic fibrosis (CF) patients in relationship to their EFA status (eicosatrienoic/arachidonic acid ratio) and compare them with those of 10 healthy siblings (SIB) and of 10 unrelated controls. In 7 EFA-deficient (EFAD) and 10 EFA-sufficient (EFAS) patients, hypocholesterolemia was associated with a decrease of HDL-cholesterol and of LDL-cholesterol which was more marked in the EFAD group. Similarly, although triglyceride enrichment of VLDL, LDL, HDL2, and HDL3 with a concomitant reduction of cholesteryl esters from all particles except HDL2 was observed in both CF groups, it was more sizable in the EFAD patients. These changes led to an increase in the particle size of VLDL, LDL, and HDL2 whereas the distribution of HDL3 was skewed to smaller particles. Alterations in the apoprotein composition of particles were greater in EFAD than in EFAS. A decrease of total postheparin lipolytic activity was observed in the two groups of CF patients as well as in siblings. It was entirely accounted for by hepatic lipase (mumol FFA/ml per h) which was more severely diminished in EFAD (2.8 +/- 0.6) than in EFAS (4.4 +/- 0.7) and SIB (5.1 +/- 0.5). Although the two groups of CF children differed in terms of growth, severity of malabsorption, and vitamin E status, these data suggest that disturbance of lipoprotein concentration, composition, size, and metabolism (hepatic lipase) may be in part related to EFA deficiency. Further studies are necessary to explore the effect of EFA deficiency on hepatic lipase activity.

Adolescent↗
PubMed1989

Decompensated cardiomyopathy mimicking hepatitis in a 13-year-old girl.

The name of a 13-year-old girl diagnosed as having idiopathic dilated cardiomyopathy was removed from the cardiac transplant list because a hepatitis-like picture developed that coincided with evidence of decompensation of her cardiac function. On admission, there was only modest evidence of cytolysis (ALT level, 115 U/L) and of cholestasis (bilirubin level, 3.0 mg/dl), but there was severe prolongation of her prothrombin time (28 s). This was followed by elevation of both her transaminases and bilirubin levels. A liver biopsy sample showed extensive necrosis involving both the central and midlobular zones, while periportal areas revealed dilated sinusoids and steatotic multinucleated hepatocytes. A brief improvement of both her liver and her heart was followed by rapid deterioration of the functions of both. Attention is drawn to the relationship between reduced cardiac output and hepatic dysfunction secondary to massive cytolysis.

Adolescent↗
PubMed1989

Meconium ileus and its equivalent as a risk factor for the development of cirrhosis: an autopsy study in cystic fibrosis.

Although dehydrated obstructing mucus is thought to account for the obstructive pathology involving the lungs, the pancreas, the reproductive system, and the intestinal tract, its relationship with CF-associated liver disease remains largely hypothetical and little is known about possible risk factors. Complete clinical and autopsy records were available in 38 of 73 deaths occurring over a 10-year period. The liver was normal in only five cases, and they were all infants. Steatosis was the only lesion present in 9, hypoxic liver disease was documented in 8, and biliary cirrhosis in 16 (focal in 10 and multilobular in 6). There was no relationship between the presence of cirrhosis, gallbladder abnormalities, age at death, and clinical status recorded during the year precoding their demise. Mucus plugs characterized by amorphous eosinophilic material within proliferated bile ductules were present in 75% of children with focal or multilobular biliary cirrhosis as opposed to 14% in those without (p = 0.015). A history of meconium ileus or its equivalent was recorded more frequently (p = 0.038) in those with cirrhosis. Finally, biliary cirrhosis was invariably present when there was a history of meconium ileus or its equivalent and when mucus plugs were noted. These findings suggest that patients with intestinal obstruction are at greater risk for the development of cirrhosis and that strategies should be developed to increase the detergent capacity of bile and its flow in order to decrease the viscosity of mucus in the biliary tree.

Bile↗
PubMed1988

Cholesterol synthesis in the pathogenesis of lithocholic acid-induced cholestasis.

Lithocholic acid (LCA)-induced intrahepatic cholestasis is associated with increased de novo synthesis of hepatic cholesterol and augmented cholesterol content of the liver cell plasma membrane fraction enriched in bile canalicular complexes (BCM). To determine whether inhibition of cholesterol synthesis could prevent LCA-induced cholestasis, adult male Wistar rats were treated daily with the hypocholesterolemic agents, clofibrate (250 mg/kg) or mevinolin (25 mg/kg), for one, two or four days. After bile duct cannulation and bile collection for one hr, the animals were injected intravenously with 120 mumoles/kg of LCA or its carrier (albumin). Cholesterol synthesis was measured in liver homogenates, and its contribution to the BCM was estimated. LCA reduced bile flow by 51%, 35% and 25% after clofibrate pretreatment for one, two and four days, respectively, and by 51%, 30% and 42% in mevinolin-pretreated animals after one, two and four days. In control animals, cholesterol synthesis and the contribution of newly synthesized cholesterol in the BCM were increased after LCA injection. However, despite that cholesterol synthesis and the contribution of newly synthesized cholesterol in the BCM were reduced in drug-pretreated rats, LCA injection caused a relative increase in these parameters of a magnitude similar to that observed in controls. Thus, the ability of LCA injection to augment de novo cholesterol synthesis and its transport to the BCM may be an important pathogenetic step in the development of cholestasis.

Animals↗
PubMed1988

Lipid abnormalities in pancreatic tissue of streptozotocin-induced diabetic rats.

Pancreatic lipid and fatty acid composition was determined in streptozotocin-induced diabetic rats and compared to control and insulin-treated diabetic rats. A pronounced decrease of total fatty acids was recorded and mainly accounted for by a drop of fatty acids in glycerides. Cholesterol, on the other hand, was significantly increased two- to three-fold, leading to an elevated cholesterol/phospholipid ratio. Morpho-cytochemical studies confirmed these findings because the multiple lipid droplets present in acinar cells of diabetic animals were found to be of cholesterol nature. The major alterations in phospholipid-fatty acid composition were characterized by an increase of linoleate coupled to a decrease of monounsaturates and arachidonate, suggesting defective metabolism of saturates and of linoleate. This was further supported by fatty acid ratios that suggested low delta 5 and delta 9 desaturation. Daily administration of insulin for 10 days restored and overcorrected the various lipid alterations. This study suggests that there are alterations in lipid composition and metabolism in the exocrine pancreas of chronic streptozotocin-induced diabetic rats. Their possible role in the mechanism regulating pancreatic function and secretion remains to be elucidated.

Animals↗
PubMed1988

Chronic intermittent elemental diet improves growth failure in children with Crohn's disease.

Growth failure often complicates Crohn's disease in pediatric patients and is principally due to inadequate caloric intake. To assess whether intermittent courses of an elemental diet could reestablish growth, 8 children (aged 9.8-14.2 yr) with Crohn's disease and growth failure entered into a prospective trial. Each patient was studied during an observation year on standard therapy, then for an experimental year during which they received enteral elemental diet 1 out of 4 mo. An age- and disease-matched control group of 4 patients was treated by conventional medical therapy during both years. Elemental diet therapy was administered nocturnally, at home, by continuous nasogastric infusion and increased the daily caloric intake by 25% (p less than 0.01). Anthropometric measurements demonstrated significant height and weight gains in the elemental diet group vs. controls (p less than 0.01). Crohn's disease activity index and prednisone intake decreased significantly in patients receiving elemental diet therapy when compared with themselves and with controls on conventional medical therapy (p less than 0.05). In contrast, the rate of pubertal development was similar in both groups irrespective of the treatment modality. This study demonstrates that chronic intermittent elemental diet effectively reverses growth arrest, while decreasing prednisone requirements and Crohn's disease activity index in pediatric Crohn's disease patients prior to puberty.

Adolescent↗
PubMed1988

Steatorrhea and disorders of chylomicron synthesis and secretion.

Knowledge concerning the absorptive phase of fat remains relatively scanty as compared to the wealth of information available on the digestive phase. However, the past years have seen important developments in our understanding of chylomicron formation and secretion. This has come about thanks to clinical studies of rare congenital disorders of chylomicron synthesis and exocytosis and to the creation of experimental models.

Celiac Disease↗
PubMed1988

Digestive and absorptive phase anomalies associated with the exocrine pancreatic insufficiency of cystic fibrosis.

The pancreas has an enormous reserve capacity, and significant malabsorption usually signals complete absence of exocrine function. However, there is evidence that acid lipases of nonpancreatic origin play an important compensatory role. Complete duodenal hydrolysis of fat requires a series of complex interdependent physicochemical events involving pancreatic lipase, colipase, phospholipase A2, and bile salts in an environment where the pH must be close to neutrality. Lipolytic products must then be shuttled through the unstirred water layer to the surface of the microvillus membrane by ionized bile salts, which must be present in sufficient concentrations to form micelles. In pancreatic insufficiency, there is not only a defective lipolytic phase but also an impaired micellar phase. The output of bile salts is decreased because of increased fecal loss. Furthermore, a significant percentage of bile salts precipitate because the duodenum is acidic and there is a large predominance of glycine conjugates. Although much less work has been done on the absorptive phase of patients with pancreatic insufficiency, there is tentative evidence that defective phospholipid absorption, essential fatty acid deficiency, and protein malnutrition could impair the absorptive phase, particularly chylomicron formation. Although significant advances have been made in our understanding of factors responsible for malabsorption associated with pancreatic insufficiency, much remains to be done for the further delineation of defects. It is hoped that this will lead to further refinements of enzyme preparations and to new strategies of intervention.

Cystic Fibrosis↗
PubMed1988

The influence of taurine on the bile acid maximum secretory rate in the guinea pig.

In view of the effect of taurine feeding on the cholestasis induced by sulfated lithocholate in the guinea pig, it was of interest to explore the influence of taurine on the bile acid secretory maximum (SRm) of chenodeoxycholic acid and of its glycine and taurine conjugates. Bile acid secretory rate measured in response to stepwise increasing rates showed for chenodeoxcholic acid an SRm of 147 +/- 6 nmol/min/g liver and any SRm that was higher (p less than 0.01) for taurine than for glycine (426 +/- 21 versus 327 +/- 24 nmol/min/g liver). Pretreatment for 3 days with taurine 0.5% in drinking water led to a 70% increase of the SRm for chenodeoxycholic acid. Analysis of the biliary bile acids after supplemental taurine demonstrated a large increment of tauroconjugates and no change in the percent of free bile acids or of sulfated forms. Experiments with labeled chenodeoxycholic acid showed no difference in the distribution of radioactivity between total liver, blood, bile, and urine on and off taurine thereby suggesting that neither sinusoidal uptake nor translocation across the cell were factors responsible for the difference in SRm. Inasmuch as taurine feeding increased the SRm for glycine by 30% and for taurine by 25%, it is suggested that taurine augments the canalicular excretion of bile acids that represents the rate-limiting step in the transfer of bile acids from blood into bile through a mechanism that cannot be explained only by a modification of the conjugation pattern.

Animals↗
PubMed1988

Contribution of the fluid phase endocytosis to bile flow in cholestasis and choleresis in rats.

Using a single iv injection of 1 mg Evans blue dye/100 g body wt in rats, the contribution of the fluid phase endocytosis to bile flow was estimated. In control rats, this pathway contributed 2-4% of the bile flow or 10-20 microliter/hr/100 g body wt. This contribution was not affected by cholestasis induced by taurolithocholic acid or bile duct obstruction or by choleresis induced by dehydrocholic acid. It is concluded that fluid phase endocytosis does not significantly influence bile formation but, rather, may be implicated in the remodeling of liver cell plasma membranes.

Animals↗
PubMed1988

Circulating lipids and lipoproteins in glycogen storage disease type I with nocturnal intragastric feeding.

With the advent of nocturnal intragastric feeding which protects against acute metabolic complications and promotes growth, patients with glycogen storage disease type I are attracting less attention. However, several biochemical alterations persist and suggest that the long-term risk of atherosclerotic heart disease remains high. Persisting hypertriglyceridemia and hypercholesterolemia were found in seven glycogen storage disease type I subjects, six of them following 5-6 yr of nocturnal intragastric feeding. When compared to ten age-matched controls, the patients showed significantly (P less than 0.001) higher low density lipoprotein cholesterol (LDL-C) (247.7 +/- 46.8 vs. 115.3 +/- 5.0 mg/dl) and lower high density lipoprotein cholesterol (HDL-C) (26.4 +/- 3.4 vs. 55.8 +/- 2.9 mg/dl). Triglyceride (TG) enrichment with cholesteryl ester depletion characterized the lipoprotein classes. The diameters of very low density lipoproteins (VLDL) and LDL were larger, while that of HDL was smaller and consistent with the predominance of the HDL3 subclass and a lower apoA-I/apoA-II ratio. The raised levels of TG appeared attributable not only to the well-described lipogenesis, but also to impaired catabolism of fat, as evidenced by the significantly (P less than 0.001) decreased activity of both peripheral lipoprotein lipase (3.17 +/- 0.43 vs. 14.15 +/- 0.50 mumol FFA.ml-1.hr-1) and hepatic lipase (1.88 +/- 0.30 vs. 4.83 +/- 0.90). This may well explain the high concentration of intermediate density lipoprotein (IDL) and the impaired conversion of HDL3 to HDL2. Low apoC-II/apoC-III1 could be related to defective lipoprotein lipase activity. These data suggest that glycogen storage disease type I patients on nocturnal intragastric feeding remain at risk for atherosclerosis and its complications.

Adolescent↗
PubMed1988

Specific methylation of plasma nonesterified fatty acids in a one-step reaction.

Analysis of plasma nonesterified fatty acids (NEFA) by gas-liquid chromatography requires procedures that are both lengthy and cumbersome. A 45-min direct methylation procedure was carried out at 24-29 degrees C on 150 microliter of plasma added with an internal standard in 5.0 ml of methanol-acetyl chloride 50:1 (v/v). To stop the reaction, 3 ml of 6.0% K2CO3 was added. After addition of 150 microliter of hexane, shaking and centrifugation, an aliquot of the upper phase was injected into the gas chromatograph. The specificity of the methylation reaction for NEFA without hydrolysis of other classes of plasma lipids was substantiated with appropriate standards. This one-step specific methylation procedure is superior to currently used methods.

Chromatography, Gas↗
PubMed1987

Nutritional therapy of Crohn's disease in childhood.

Crohn's disease is a chronic, incurable inflammatory bowel disease commonly diagnosed in childhood and adolescence. Growth failure represents a common, serious complication unique to the pediatric age group. Although the etiology of growth failure is multifactorial, malnutrition due to inadequate nutrient intake is the primary cause. Recent studies have demonstrated that nutritional supplementation through an enteral or parenteral route restores body composition and reverses linear and ponderal growth failure. The development of elemental diets that can be administered nasogastrically at home has afforded a more practical, less expensive, and less hazardous method of providing Crohn's disease patients with nutritional supplementation and bowel rest. Elemental-diet therapy has also been shown to be a safe, effective method of inducing a remission in acute Crohn's disease. Further studies are required to develop optimal nutritional therapy which may sustain long-term remission in this disease.

Child↗
PubMed1987

Plasma and lipoprotein fatty acid composition in glycogen storage disease type I.

Nocturnal intragastric feeding has been shown to be an effective means to improve clinical and biochemical features in glycogen storage disease type I (GSD-I). In this study, we investigated the fatty acid patterns in a whole plasma and in circulating lipoproteins in patients on this therapy. The results demonstrated massive concentration of total fatty acids coupled with higher levels of triglycerides, free cholesterol, cholesterol ester and phospholipids. This hyperlipidemia involved all fatty acids without distinction of carbon or bond numbers. However, the increase was more pronounced for saturated than polyunsaturated fatty acids, as was demonstrated by the ratios of both oleic acid to linoleic acid (1.91 +/- 0.40 vs 0.80 +/- 0.09 in controls) and of omega 3 + omega 6 to omega 9 fatty acid families (0.92 +/- 0.11 vs 1.66 +/- 0.08 in controls). The fatty acid patterns in very low (VLDL), low (LDL) and high (HDL) density lipoprotein showed substantial differences in composition, reflecting an association between an abnormal lipoprotein pattern and essential fatty acid deficiency. Furthermore, GSD-I patients exhibited a significant increase in VLDL (17 +/- 2 vs 47 +/- 7 mg/dl) and LDL cholesterol (124 +/- 7 vs 206 +/- 24 mg/dl), coupled with a decrease in HDL cholesterol (49 +/- 4 vs 28 +/- 3 mg/dl). These data documenting high LDL cholesterol and low HDL cholesterol associated with an increased concentration and proportion of saturated fatty acids suggest that GSD-I patients on nocturnal intragastric feeding are at high risk for atherosclerosis and its complications.

Adolescent↗
PubMed1987

Malabsorption, hypocholesterolemia, and fat-filled enterocytes with increased intestinal apoprotein B. Chylomicron retention disease.

Eight infants presented with a malabsorption syndrome, normal fasting triglycerides, hypocholesterolemia (64.3 +/- 10.0 mg/dl), and deficiency of vitamins A and E. Plasma low-density lipoprotein, apolipoprotein B, and apolipoprotein A-I were decreased. After a fatty meal, plasma triglycerides did not increase and chylomicrons could not be identified. Lipoprotein composition was characterized by normal apoproteins, high phospholipids, and low cholesterol. Increased triglycerides were present in low-density lipoproteins. Immunoperoxidase localization of apolipoprotein B on fasting biopsy specimens showed increased staining of the lipid-laden intestinal epithelial cells compared to normals. On electron microscopy after a fat load, the enterocytes contained large numbers of fat particles vesiculating the endoplasmic reticulum. These particles, morphologically similar to chylomicrons, were also present as aggregates of well-individualized lipid droplets within dilated vesicles in the Golgi zone, but were not seen in the intercellular spaces and lacteals. This recessively transmitted condition differs from abetalipoproteinemia and from the homozygous form of hypobetalipoproteinemia and may be caused by a defect in the final assembly of chylomicrons or in the mechanism of their exocytosis.

Apolipoproteins B↗
PubMed1987

Absence of intestinal synthesis of apolipoprotein B-48 in two cases of abetalipoproteinemia.

Previous studies have reported that the absence of chylomicron, very-low-density lipoprotein, and low-density lipoprotein in abetalipoproteinemia is a consequence of apoprotein B (apo B) deficiency. Although the absence of apo B from the intestine has been shown by immunofluorescence, the antiserum used was raised against low-density lipoprotein apo B. Therefore, the precise nature of the underlying defect remains unknown, given that the postulated gene mutation could prevent the synthesis of the molecular form of apo B specific for chylomicrons, apo B-48, or produce an unstable aberrant form of apo B particle. This report concerns 2 girls aged 5.5 and 4.75 with well-documented clinical and biological manifestations of the disease in whom there was no immunologically detectable plasma apo B-48 and apo B-100. Their cultured jejunal explants incubated with [14C]palmitate showed slight decrease in the esterification of triglycerides, phospholipids, and cholesteryl esters. However, only traces of triglycerides and small amounts of cholesteryl esters were found in the culture medium in contrast to phospholipids, which were readily exported. Protein synthesis as assessed by [3H]leucine incorporation by explants was normal and only modestly diminished in the fat chylomicronlike fraction floated from the sonicated explants. However, there was no radioactivity at the electrophoretic position of apo B-100 and apo B-48. Immunologic confirmation of the absence of these two apoproteins was obtained by Western blots. These data confirm the hypothesis that in certain cases of abetalipoproteinemia the intestinal defect results from the lack of synthesis of apo B-48.

Abetalipoproteinemia↗
PubMed1987

Storage of medium-chain triglycerides in adipose tissue of orally fed infants.

The effect of the fatty acid content of the diet on that of adipose tissue was studied in 5 newborn infants studied prior to feeding and 30 infants fed ad libitum from birth with either human milk or a commercial formula as the sole nutrient. Significant positive linear correlations of dietary intake on adipose tissue content of fatty acids were found for both long- and medium-chain fatty acids (MCFA). Infants stored up to 12% of MCFAs in their subcutaneous fat. The technique of direct transesterification improved the recovery of the volatile MCFAs and could explain the finding that medium-chain triglyceride storage in adipose tissue is more extensive than in previous reports. This study documents that MCFAs are not used solely as a source of energy: they can be reesterified or serve for chain elongation, before being deposited in fat stores.

Adipose Tissue↗