Isolation and characterization of hepatic Golgi lipoproteins from hypercholesterolemic rats.

The feeding of cholesterol-rich diets alters the serum lipoproteins of a number of mammalian species. These lipoproteins are characterized by the presence of several classes of particles enriched in cholesteryl esters and apolipoprotein E (apo E). It was the aim of this study to determine whether one or more of these particles arises by de novo hepatic synthesis by characterizing nascent lipoproteins isolated from the hepatic Golgi apparatus of hypercholesterolemic rats. Characterization of these lipoproteins afforded the opportunity to assess morphologic, biochemical, and biophysical properties of newly synthesized lipoproteins before enzymatic alterations and apoprotein transfer known to occur after secretion into the plasma compartment. Golgi very low density lipoproteins (VLDL, d < 1.006 g/ml) from hypercholesterolemic rats contained nearly four times the total cholesterol mass found in control Golgi VLDL. They exhibited electrophoretic mobility intermediate between beta and pre-beta and were devoid of apo C. A second population of hepatic Golgi lipoproteins was isolated from hypercholesterolemic rats at 1.006--1.040 g/ml d. These low density lipoproteins were smaller than VLDL, displayed beta electrophoretic mobility, were enriched in cholesteryl esters, and contained apo E as well as apo B. The fatty acid composition of the core lipids of the nascent lipoproteins was found to reflect that of dietary triglyceride. The liver of the hypercholesterolemic rat thus plays an active role in dietary-induced hypercholesterolemia by synthesizing a modified VLDL and a low density lipoprotein resembling serum low density lipoprotein.

Effects of several common long chain fatty acids on the properties and lipid composition of the very low density lipoprotein secreted by the perfused rat liver.

1. Livers from normal fed male rats were perfused in vitro with a bloodless medium which contained intially 3% bovine serum albumin and 100 mg% glucose. Albumin alone, or myristate (14 : 0), palmitate (16 : 0), palmitoleate (16 : 1), stearate (18 : 0), oleate (18 : 1), or linoleate (18:2) was infused at a constant rate (496 mumol/4 h), as a complex with albumin, during the experiment. 2. The very low density lipoprotein secreted by the liver after infusion of unsaturated fatty acids (16 : 1, 18 :1, 18 : 2) has a faster rate-zonal mobility in the ultracentrifuge and is, therefore, probably a larger particle with fewer moles of phospholipid and cholesterol relative to triacyglycerol (triacyglycerol/phospholipids/cholesterol = 100/25.1/16.4) than the very low density lipoproteins produced after infusion of saturated (14 : 0, 16 : 0, 18 : 0) fatty acids (triacyglycerol/phospholipids/cholesterol = 100/30.1/19.1). The molar ratio of phosphoipids/cholesterol of the very low density lipoprotein was similar regardless of which fatty acid was infused. The predominant fatty acid of the very low density lipoprotein or hepatic triacyglycerol, in all cases, was the infused acid. 3. We conclude that free fatty acid regulates the quantity and proportions of triacyglycerol, phospholipids, and cholesterol secreted by the liver in the very low density lipoprotein, and therefore, may secondarily influence concentrations of lipids in the very low density lipoprotein and other plasma lipoproteins circulating in vivo.

Effects of caffeine on plasma free fatty acids, urinary catecholamines, and drug binding.

The effects of caffeine (250 mg orally) on plasma free fatty acids (FFA), urinary catecholamines, and drug binding were studied in 16 normal subjects (six men, five women on oral contraceptives, and five women not on oral contraceptives). FFA doubled 1 hr after caffeine, and remained elevated for at least 4 hr. with elevation of each FFA. Urinary excretion of epinephrine and dopamine increased (p<0.05) in the first 2 hr. returning to baseline in the next 2 hr. Plasma binding of chlordiazepoxide, diaxepam, and propranolol was estimated in each of the hourly plasma samples after caffeine; there was no change in percent unbound drug in any of the samples. In vitro addition of oleic acid to plasma samples of four subjects caused a step-wise increase in percent unbound fraction of all three drugs whereas in vitro addition of caffeine did not further alter drug binding. In our study circulating plasma FFA and urinary catecholamine levels were elevated after caffeine ingestion. In spite of a rise in FFA, there was, however, no change in plasma binding of chlordiazepoxide, diazepam, or propranolol.

Effectiveness of cimetidine as an adjunct to supplemental pancreatic enzymes in patients with cystic fibrosis.

The effectiveness and safety of the use of cimetidine as an adjunct to pancreatic enzymes was evaluated in eight patients with cystic fibrosis having pancreatic insufficiency. Cimetidine (300 mg, three times a day) was given for a 6-week period during which the patients demonstrated a significant weight gain (P < 0.05) and reduction of steatorrhea (P < 0.01). Data suggesting an early correction of the abnormal fatty acid composition of plasma lipids were observed. No side effects were apparent during the clinical trial. These results demonstrate the beneficial effects of the use of cimetidine in patients with cystic fibrosis and indicate the need for long-term clinical trials.

Enteral-tube feeding as adjunct therapy in malnourished patients with cystic fibrosis: a clinical study and literature review.

Eight children (aged 8 mo to 13 yr) with cystic fibrosis (CF) and growth failure were given home nocturnal nasogastric feeding of an elemental diet for 3 mo and re-evaluated 3 mo after cessation of tube feeding. An increase in energy intake (p less than 0.05) resulted in increased serum transferrin (p less than 0.005), retinol-binding protein (p less than 0.05), and clinical scores (p less than 0.05) during the study. Height and growth velocity increased by 60% (p less than 0.05), and weight growth velocity increased by 63%. Arm-muscle circumference, triceps skinfolds, serum albumin, vitamin A, vitamin E, zinc, and copper did not change significantly during tube feeding. Nocturnal feeding were safe and effective in promoting growth; however, most children with severe lung disease did not sustain the gains after cessation of tube feeding. Our findings indicate that continued nutritional support is needed to maintain the growth in malnourished children with severe lung disease.

Nitric oxide reduces tumor cell adhesion to isolated rat postcapillary venules.

Adhesion of circulating tumor cells to microvascular endothelium plays an important role in tumor metastasis to distant organs. The purpose of this study was to determine whether nitric oxide (NO) would attenuate tumor cell adhesion (TCA) to naive or lipopolysaccharide (LPS)-treated postcapillary venules. A melanoma cell line, RPMI 1846, was shown to be much more adhesive to postcapillary venules isolated from rat mesentery than to corresponding precapillary arterioles. Although venules exposed to LPS for 4 h demonstrated an increased adhesivity for the melanoma cells, TCA to LPS-treated arterioles was not altered. Isolated venules exposed to DETA/NO (1 mM), an NO donor, for 30 min prior to tumor cell perfusion prevented the increment in adhesion induced by LPS and attenuated TCA to naive postcapillary venules. While L-arginine (100 microM), an NO precursor, failed to decrease TCA to naive postcapillary venules, this treatment abolished LPS-stimulated TCA to postcapillary venules. The effect of L-arginine was reversed by administration of N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM), an NO synthase (NOS) inhibitor. These observations indicate that both exogenous and endogenous NO modulate TCA to postcapillary venules. To assess the role of NO-induced activation of cGMP in the reduction in TCA produced by DETA/NO, two additional series of experiments were conducted. In the first series, LY-83583 (10 microM), a guanylyl cyclase inhibitor, was shown to completely reverse the effect of DETA/NO on TCA to both naive and LPS-activated postcapillary venules. On the other hand, administration of 8-bromoguanosine 3',5'-cyclic monophosphate (8-B-cGMP) (1 mM), a cell permeant cGMP analog, mimicked the effect of DETA/NO and reduced TCA to LPS-stimulated postcapillary venules. These data suggest that (a) tumor cells are more likely to adhere to postcapillary venules than to corresponding precapillary arterioles, (b) LPS enhances TCA to postcapillary venules, (c) both exogenously applied (DETA/NO) and endogenously generated (L-arginine) NO attenuate the enhanced adhesion induced by LPS, but only DETA/NO reduced TCA to naive postcapillary venules, and (d) the NO-induced reduction in TCA to LPS-activated postcapillary venules occurs by a cGMP-dependent mechanism.

Fatty acid composition of erythrocyte phospholipids from patients with cystic fibrosis.

The phospholipid fatty acid composition of erythrocytes from patients with cystic fibrosis with pancreatic insufficiency, patients with cystic fibrosis with normal pancreatic enzyme function, and normal subjects was determined. Increased percentages of palmitoleic acid and total eicosatrienoic acid and a decreased percentage of linoleic acid were observed only in the cystic fibrosis patients with pancreatic insufficiency.

Effects of dietary triglyceride on the properties and lipid composition of plasma lipoproteins: acute experiments in rats fed safflower oil.

Male rats were administered 1.5 ml safflower oil by gastric intubation 0, 4, and 8 hr after a 16 hr fast. Plasma, liver, and adipose tissue were collected 16 hr after the last fatty meal. Rats fasted for 16 hr served as controls. Following fat feeding, the fatty acid composition of the very low density lipoprotein, triglyceride, and hepatic triglyceride were similar, as were the percentages of 18:2 in the very low density lipoprotein and hepatic cholesteryl esters. The phospholipids of liver and plasma lipoproteins were similar in the control groups, except that more 16:0 was present in the plasma lipoproteins. After fat feeding, the plasma lipoproein phospholipids were enriched with 18:2 more than were the hepatic phospholipids. Furthermore, the percentage of 18:2 in phospholipid was much less than in triglyceride or cholesteryl esters. Clearly, esterified lipids of liver and plasma lipoproteins (very low density lipoprotein, low density lipoprotein, and high density lipoprotein), and to a lesser extent, adipose tissue, were enriched with 18:2 derived from dietary triglyceride fatty acid even 16 hr after the terminal meal. A major proportion of the very low density lipoprotein isolated by ultracentrifugation in zonal rotors from plasma of fat fed animals had a faster rate-zonal mobility than did the very low density lipoprotein isolated from plasma of control animals. The very low density lipoprotein isolated from plasma of fat fed rats contained fewer moles of phospholipids, cholesterol, and cholesteryl esters, relative to triglyceride than did the very low density lipoprotein from plasma of animals not receiving safflower oil. The molar ratio triglyceride:phospholipid:cholesterol:cholesterol esters in the very low denity lipoprotein was 100:42.0:22.1:44.5 in the control group and 100:35.4:17.8:19.5 in the fat fed animals. It is postulated that an important biochemical mechanism by which dietary triglyceride fatty acids consumed by the animal over a long period of time alter plasma concentrations of triglyceride, phospholipids, and cholesterol esters is the directive influence of plasma free fatty acid, derived from dietary triglyceride, on the secretion of very low density lipoprotein lipids by the liver.

Gastrointestinal disorders: the role of diet in cause and management.

Diet has a definite role in certain gastrointestinal disorders, and dietary manipulation often is beneficial. In other cases, such as peptic ulcer, traditional dietary therapy cannot be justified by available evidence.

Disappearing liver sign.

The development of a pneumothorax is a recognized complication of ultrasound-guided percutaneous liver biopsy. A way of detecting such a complication using real-time ultrasound is described, whereby the well-visualized liver disappears from the monitor screen. We also discuss the reasons for this occurrence.

Colonic lipomas: clinical significance and management.

Colonic lipomas are uncommon tumors but do constitute the most common nonepithelial tumor of the gastrointestinal tract. They tend to occur in an older population and rarely cause symptoms. However, if a lipoma discovered by barium enema or colonoscopy is causing symptoms of obstruction or bleeding, the tumors may require surgical removal. Rarely, as in our patient, the bleeding lipoma may be sufficiently pedunculated to allow safe colonoscopic removal. In general, lipomas of the colon are curiosities that must be distinguished from adenomatous polyps.

The left-sided pancreas.

Ultrasonography (US) performed in nine patients (two with pancreatic carcinoma, one with hepatomegaly, six with no relevant abdominal disease) showed the pancreas to lie wholly to the left of the aorta. This not uncommon location may give rise to difficulty in demonstrating the pancreas on real-time US scans. The superior mesenteric vessels and splenic vein remain useful landmarks for locating the head of the pancreas in this position.

Computed tomography features of small bowel volvulus.

A case of small bowel volvulus in an adult is presented. The established CT signs of small bowel volvulus are discussed. These include an abnormal orientation of the superior mesenteric artery to the superior mesenteric vein; the whirl sign, the triangle sign and the beak sign.

Use of retrograde cholangiography in guiding radiotherapy of obstructive jaundice due to tumor.

A patient with oat cell carcinoma of the lung which was responsive to radiotherapy developed jaundice. Endoscopic retrograde pancreatocholangiography (ERCP) revealed compression of the distal common bile duct. Radiotherapy to this area produced prompt and prolonged relief of the obstructive jaundice. The use of ERCP which led to significant palliation in a patient with known inoperable cancer makes this case worthy of note.

Diffuse fatty infiltration of the liver: pitfalls in computed tomography diagnosis.

The presence of a fatty liver often complicates the interpretation of abdominal computed tomography (CT). Abnormalities in or adjacent to the liver, including dilated bile ducts, liver masses and subphrenic collections, may be masked by the fatty liver. Furthermore, normal structures may simulate pathological conditions. Five cases are presented to illustrate some of these diagnostic pitfalls.

Acquired double pylorus.

We have reported two cases of double pylorus or duplicated pyloric channel as an unusual complication of peptic ulcer disease. It is usually noted as an incidental finding on x-ray films or at endoscopy. Double pylorus seems to be an acquired lesion arising from gastric ulceration and does not necessarily require surgical correction.

Essential fatty acid deficiency during total parenteral nutrition.

Essential fatty acid (EFA) deficiency has become a clinical problem since the advent of fat-free total parenteral nutrition (TPN). The following study was done to determine the minimum fat requirements for patients receiving continuous TPN solution. Seventy-seven patients who had 97 courses of TPN of at least 14 days duration were prospectively studied. The following fat supplementation was given: a) none, b) 10% soybean oil emulsion intravenously at fixed dosage, c) fat from an oral diet, or d) intravenous and oral fat. No patient was EFA deficient before the onset of TPN. EFA deficiency was prevented when at least 3.2% of total calories were given as intravenous fat or at least 15% as oral fat. Lesser amounts of fat decreased the rate of EFA deficiency development but did not prevent it from occurring. The 7.7 g/day of linoleic acid provided in 1000 ml per week of 10% soybean oil emulsion provides adequate fat to prevent EFA deficiency.

Variceal bleeding from an ileostomy stoma.

Patients with portal hypertension due to cirrhosis commonly have bleeding from varices. In patients with a total colectomy, ileal varices can be a site of bleeding in cases of portal hypertension. Proper diagnosis requires studying the venous phase of the mesenteric arteriogram to show ileal varices, and carefully inspecting the mucocutaneous region of the ileal stoma for venous bleeding sites. Bleeding from ileal varices can be managed by either local control or portal vein decompression.