A probable defect in the beta-oxidation of lipids in rats fed alcohol for 6 months.

Studies on fatty acid oxidation were made in rats fed for 6 months on a liquid diet containing 15% total calories as ethanol. After 6 months, a marked diminution was observed in the in vivo production of 14CO2 from labeled palmitate and octanoate in the ethanol-fed animals compared to their pair-fed isocaloric controls not receiving alcohol. Similar results were obtained in 14CO2 formation from 14C-fatty acids using liver mitochondria from these ethanol-fed rats after 6 months. The effect on octanoate beta-oxidation was larger than that for palmitate. Addition of purified acyl CoA dehydrogenase complexes and additional electron transfer flavoprotein complex to the mitochondria suggested that the ethanol-fed animals could have been deficient in the medium-chain acyl CoA-dehydrogenase complex.

Lipid composition and de novo lipid biosynthesis of human palmar fat in Dupuytren's disease.

Seventy-two surgically obtained Dupuytren's disease palmar-fat (DDPF) specimens and 18 location-matched specimens from patients not suffering from this disease (controls) were studied for their total lipid composition and de novo lipogenic activity. Incubation of "DDPF" with 1-[14C]acetate in oxygen produced [14C]palmitate and [14C]stearate in approximately equal yields as those obtained from "controls." No [14C]octanate was formed in any of the palmar-fat preparations. The lipids and fatty acid analysis revealed differences: (a) DDPF specimens were richer in free fatty acids, methyl esters of fatty acids and free-cholesterol than specimens of controls. (b) DDPF specimens contained less phospholipids. (c) DDPF specimens showed a significantly higher content of octanoate and other short-chain fatty acids than specimens of controls. The above findings are not incompatible with the results expected if some mild hypoxia occurred in DDPF; this has been suggested in the statistical correlations observed for this disease and alcoholism with liver involvement.

[Labelled CO2 breath-tests in gastroenterology (author's transl)]. / Le breath test CO2 marqué en hépato-gastro-entérologie.

The use of a few microcuries of 14C labelled molecules with very short biological half-life for breath-tests gives no more body irradiation than 10 minutes' exposure to the sun. Yet it provides the gastroenterologist with accurate information. Detection and identification of fat malabsorption are easy when 3 labelled lipids are used. Glycine 1 14C cholate administered orally offers a simple, rapid and effective screening technique for the detection of increased bile salt deconjugation and may provide a valuable diagnostic supplement in the study of steatorrhea after ileal resection, bypass or bacterial overgrowth. The clearance of labelled aminopyrine can be decreased in hepatocellular dysfunction or increased in some alcoholic patients or in patients receiving phenobarbitone. Tracer doses of labelled ethanol were used to study the metabolism of ethanol by the liver in alcoholic patients. Chronic ingestion of alcohol stimulates the activity of microsomal drug-metabolising enzymes in both non-cirrhotic and cirrhotic patients; this response is lost in acute liver damage and in chronic alcoholic disease with severe hepatic dysfunction. The CO2-labelled breath-tests are non-invasive, effective and inexpensive. The forthcoming replacement of 14C by non-radioactive 13C or briefly radioactive 11C will render these tests even more attractive.

[Hyperoctanoatemia and the hepatic encephalopathy of cirrhosis. 150 dosages in 61 patients (author's transl)]. / Hyperoctanoatémie de l'encéphalopathie hépatique des cirrhoses. 150 dosages chez 61 malades.

A new and sensitive method for determination of octanoate in serum by gas-liquid chromatography is described. It was validated by mass spectrometry. Octanoate concentrations were determined in the serum of 61 fasting cirrhotic patients of which 47 also had hepatic encephalopathy. Concentrations in arterial and venous blood were higher in cirrhotic patients with encephalopathy than in those without and higher in the latter than in controls. Arterial concentrations were higher than venous concentrations and octanoate and ammonia varied independently. A predominant endogenous origin is likely. Data obtained from studies using palmitic acid labeled at different loci suggest that recovered serum octanoate was formed mostly by incomplete oxidation of long chain fatty acids. Sodium octanoate infusion to rhesus monkeys studied polygraphically induces a temporary coma.

Sources of serum [14C]-octanoate in cirrhosis of the liver and hepatic encephalopathy.

Serum octanoate levels of patients with liver cirrhosis and hepatic encephalopathy have been shown to be three to 15 times higher than those of controls. Assays for octanoate have been modified to permit isolation of pure octanoate after GLC. Patients with these conditions were given intravenously differently labeled [14C]-palmitates; serum [14C]-octanoate was isolated in each case and shown by mass spectrometry to be authentic octanoate. [1-14C]-oleate and [1-14C]-stereate were also shown to serve as precursors of serum [14C]-octanoate. When differently labeled palmitates (1-[14C]; omega [14C]; and [14C]-uniformly labeled) were used, different yields of serum [14C]-octanoate were recovered. Octanoate samples were chemically degraded to yield individual carbons or groups of carbons. In this manner it was possible to determine the percentage distribution of the [14C] label within the octanoate carbon chain. The data obtained from these studies suggest that 60% to 80% of the serum octanoate was obtained from the incomplete beta-oxidation of long-chain fatty acids and that 20% to 40% of the octanoate may have been formed de novo.

Relapsing polyradiculitis after portocaval anastomosis.

A case of relapsing polyneuritis in a cirrhotic woman with a surgical splenorenal shunt is reported. The ultrastructural study of the nerve biopsy shows widespread segmental demyelinization with total myelin breakdown in most fibers; some Schwann cells are invaded by mononuclear cell processes. Such histological changes are characteristic of the Guillain-Barré syndrome. Alcohol and diabetes are unlikely to be the causative factors of the nerve damage. The possible role of unidentified toxic metabolites such as those which cause portosystemic encephalopathy, also present in our patient, is discussed.

A method for serum octanoate in hepatic cirrhosis and hepatic encephalopathy.

We describe a new, more efficient, and more reproducible method for determination of octanoate in serum. This method involves ethanol extraction, followed immediately by alkali addition before concentration of the extract. The concentrate is made acidic only before it is to be steam distilled (in a special all-glass apparatus with an alkali trap). The material is acidified again just before separation by gas-liquid chromatography. The yield is 89-107%. When assayed by mass spectrometry, only octanoate was found in the fraction from chromatography. Previous methods yielded only 30-55% of the expected octanoate value and the recovered materials showed impurities by mass spectrometry. Octanoate concentrations were determined in the serum of 24 fasting controls and that of 85 fasting cirrhotic patients, of whom 50 had encephalopathy. Concentrations in arterial and venous blood were significantly higher in cirrhotic patients in coma than in those not in coma, and arterial concentrations were statistically higher than venous concentrations in the cirrhotic patients.

[Quantitative study of multimolecular forms of serum gamma glutamyl transferase by polyacrylamide gel electrophoresis]. / Etude quantitative des formes multimoléculaires de la gamma-glutamyl-transférase du sérum par électrophorèse en gel de polyacrylamide

The quantitative distribution of the multimolecular forms of serum gamma-glutamyl-transferase is studied in 286 sera by acrylamide gel electrophoresis, incubation, coloration in situ, photography, slide reading and integration. In 43 normal sera, the fast fraction represents 66% of the total activity; the ratio of the mean fast fraction to the medium and slow fraction was 2. During pregnancy (53 cases), in cord blood (54 cases), in hepatic cytolysis or cholestasis (55 cases), and in secondary liver carcinoma (21 cases), this ratio is considerably lower, demonstrating the predominance of medium and slow fractions. A similar decrease in the ratio, with predominance of the medium and slow fractions was seen in 22 cases of advanced cancer without metastases in the liver.