On octanoic acid-induced hyperventilation — implications for hepatic encephalopathy and Reye's syndrome

Medium chain fatty acid sodium octanoate was infused into rabbits as a 0.2 M solution over 4 h resulting in blood and brain octanoate levels of 200-800 mumol/l. The infused animals developed marked hyperventilation leading to a mild respiratory alkalosis. Additionally, octanoate infusion brought about hyperammonemia and hyperlactate acidemia. Another group of rabbits also infused with octanoate but pretreated with indomethacin (10 mg/kg b.wt.) developed neither hyperventilation nor hyperammonemia. Therefore, the conclusion made was that octanoate causes the above mentioned disorders through stimulation of prostaglandin synthesis and especially the PGE2 synthesis. Patients with hepatic encephalopathy and Reye's syndrome have elevated levels of plasma octanoate. The present study suggests that octanoate might be the cause for both the hyperventilation and hyperammonemia observed in patients with hepatic encephalopathy and Reye's syndrome.     

Reye's syndrome in a neonate.

This case substantiates the fact that Reye's syndrome can occur in newborns. The clinical features appear to be slightly different in the neonate, in that respiratory distress was the presenting sign in this case and in the one other reported case in a newborn, with no mild preceding illness or vomiting. Thus, Reye's syndrome must be considered when a newborn presents with respiratory distress and evidence of central nervous system and hepatic involvement.     

Reye's syndrome in an adult.

Reye's syndrome (fatty infiltration of the liver with encephalopathy) is an uncommon disease of children and has not previously been noted in adult patients. We present a 25-year-old male who survived this syndrome after presenting a stuporous state. Etiologic and pathophysiologic mechanisms are considered.     

Plasma phospholipid fatty acid composition and estimated desaturase activity in heart failure patients with metabolic syndrome

Metabolic syndrome is one of the major factors to increase the incidence of heart failure. In our study, we compared plasma fatty acid compositions among heart failure patients with and without Metabolic syndrome. Fatty acid (FA) composition of plasma phospholipids was analyzed and the activities of desaturase were estimated as the ratio of substrate and product fatty acids in 85 stable heart failure patients. Fatty acid and estimated desaturase activities were further examined for their associations with Metabolic syndrome components. Heart failure patients with Metabolic syndrome showed significant changes in fatty acid composition in comparison to those without Metabolic syndrome, which had a decreased proportion of lauric acid (C12:0) and an increased proportion of dihomo-γ-linolenic acid (C20:3n-6). Also, estimated desaturase activities (D5D and D6D) were closely related to Metabolic syndrome condition among heart failure patients. The content of dihomo-γ-linolenic acid showed positive correlations with BMI, waist circumference, and plasma triglyceride levels. D6D were positively associated with plasma triglyceride levels, whereas D5D showed a negative correlation with plasma triglyceride levels and waist circumferences. The content of dihomo-γ-linolenic acid as well as estimated D6D and D5D were altered in heart failure patients with Metabolic syndrome.     

Fatty acid desaturase expression in human leucocytes correlates with plasma phospholipid fatty acid status

Associations between and changes in plasma phospholipid fatty acid (FA) concentrations and expression of delta 5 desaturase (D5D), delta 6 desaturase (D6D) and delta 9 desaturase (D9D) in leucocytes were investigated both before and during n‐3 FA supplementation for 2 weeks in 20 healthy individuals. Participants were divided into two groups depending on fish intake: one fish meal or less per week and no marine FA supplement (Lowfish, n = 9) and more than one fish meal per week and/or daily oral marine FA supplement (Highfish, n = 11). Before starting supplementation (t = 0), concentrations of n‐3 FAs were significantly lower in the Lowfish group compared to the Highfish group. During supplementation in both groups, n‐3 FAs increased, whereas n‐6 FAs decreased. D5D expression was significantly higher in Lowfish compared to Highfish at t = 0. No difference in D6D or D9D expression was observed. D5D expression was inversely correlated with EPA, DPA, DHA and total n‐3 FA, and positively correlated with the ratio total n‐6 FA/total n‐3 FA at t = 0. Expression of D5D in the Lowfish group as well as D6D in both groups significantly decreased relative to the expression at t = 0 during the first day of supplement. PUFA concentration was generally predicted by its precursor FA and D5D or D6D expression. The correlations mentioned disappeared after 2 weeks of supplementation. This indicates that steady‐state FA desaturase expression is associated with plasma phospholipid FA composition. Whether leucocyte desaturase expression may have potential as a marker of PUFA status merits further investigation.     

Fatty acid composition of plasma lipids in gout

The changes occurring in the fatty acid composition of the plasma lipids were studied in gout. The major changes consisted in an increase in oleic acid and a decrease in linoleic and arachidonic acids in most lipid fractions of plasma; linoleic acid is unchanged in plasma cholesteryl esters and in FFA while arachidonic acid does not vary only in FFA. These changes are not related either to diet or to the age of patients and are similar to those reported in atherosclerotic and diabetic patients, as well as those with cardiac ischemia. The variations observed are directly influenced by the ratio essential fatty acids/monoenoic acids and all factors affecting this ratio.     

Pentobarbital therapy for intracranial hypertension in metabolic coma. Reye's syndrome

In severe Reye's syndrome, with nonspecific intensive supportive therapy, the mortality rate approaches 75%. In many instances, death is due to uncontrolled cerebral edema and elevated intracranial pressure. (ICP). Pentobarbital therapy, sufficient to maintain a blood barbiturate level between 2.5 mg% and 4.0 mg%, was used to control ICP in seven patients with metabolic coma complicated by intracranial hypertension (intracranial pressure greater than 30 mm Hg for 30 min). The nadir of their neurological function was characterized by no response to deep pain, absent or abnormal oculocephalic responses, bilaterally dilated, unreactive pupils, and markedly irregular or absent respirations. Before barbiturate administration hyperventilation, steroids, mannitol, and other supportive therapies commonly used in Reye's syndrome were begun. After institution of pentobarbital therapy, the daily mannitol dose required to maintain the intracranial pressure below 20 mm Hg was significantly reduced (p less than 0.001), from 3.7 +/- 0.3 to 0.5 +/- 0.2 g/kg/day. All the patients survived, and six have no obvious neurological sequelae. Pentobarbital is a useful adjunct for intracranial pressure control in advanced metabolic coma.     

Altered metabolic profiles of valproic acid in a patient with Reye's syndrome

Urinary valproate metabolite and endogenous organic acid profiles in a 6-yr-old girl with Reye's syndrome were investigated by means of gas chromatography-mass spectrometry. 2-n-Propyl-3-oxovaleric acid, normally the major metabolite of valproate in man, was undetectable, while 2-n-propylglutaric acid, the end product via omega-oxidation was markedly increased. Polyunsaturated valproate was not found. Valproate-glucuronide was still found as the major metabolite. The clinical findings coupled with a greatly increased excretion of lactate and adipate was compatible with Reye's syndrome. Ketone bodies were not detectable. This case study shows that Reye's syndrome causes altered valproate metabolism, consistent with the defective mitochondrial beta-oxidation of medium chain fatty acids, and suggests that valproic acid should not be used in the treatment of seizures in patients with this syndrome.     

Critical care and anesthetic management of Reye's syndrome.

The encephalopathy of Reye's syndrome is frequently complicated by increased intracranial pressure (ICP) which may lead to death or severe neurologic sequelae. An understanding of the pathophysiology of increased ICP is necessary to prevent further increases in pressure and to reduce pressure while maintaining adequate cerebral perfusion. Four of seven children with Reye's syndrome and increased ICP survived after reduction of increased ICP by controlled hyperventilation and osmotherapy while being monitored with the Richmond intracranial bolt. Careful anesthetic and critical-care management, appropriate, reliable monitoring, and pentobarbital therapy may constitute the most successful therapy to date for patients with Reye's syndrome and increased ICP.     

Medium-chain triglycerides inhibit growth of Malassezia: implications for prevention of systemic infection.

OBJECTIVE: Lipophilic Malassezia species may induce catheter-associated sepsis in newborns and immunocompromised patients receiving parenteral lipids. Therefore, we tested whether M. furfur and six other Malassezia species can use commercially available infusions as a lipid source. DESIGN: Prospective in vitro study. SETTING: Research laboratory in a university hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: With the exception of M. restricta, all Malassezia species grow on lipid infusions. There are no substantial differences among the different brands. The most rapid growth is shown by M. furfur, which grows better on agar containing a 20% rather than a 10% lipid infusion. Growth of M. furdur and M. sympodialis can be reduced by infusions containing medium-chain triglycerides. Incubated in triglycerides, M. furfur is strongly suppressed by 50% medium-chain triglycerides and M. sympodialis by 8% medium-chain triglycerides. When medium-chain free fatty acids are added to triglycerides, both species can be suppressed by about 1% free fatty acids. CONCLUSION: Medium-chain triglycerides and medium-chain free fatty acids are toxic for Malassezia species. Commercially available infusions containing medium-chain triglycerides might be used to prevent systemic Malassezia infections.     

Fatty acid composition of human adipose tissue in different sites

The fatty acid content in human adipose tissue from different sites is studied by gas chromatography in ten subjects who had died without metabolic diseases.

In accordance with the few data in the literature, no significant differences were found between the various sites of depot fat in all the subjects examined.

However, compared to other authors, a much higher percentage of oleic acid was found. This is attributed to the different eating habits of the subjects under study.     

Fatty acid composition of lipids in biological objects in senile cataract

Fatty acid composition of plasma lipids, erythrocytes, and the lens has been determined in patients with senile cataracts. The results indicate that coronary disease is a risk factor fraught with disorders in lenticular lipid metabolism.     

Polygraphic recordings in a case of Reye's syndrome

In a comatose patient with Reye's syndrome, stimulation that increased the heart rate also produced changes in the intracranial pulsations and pressure, as well as in the electroencephalogram.     

Identification of fatty acid methyl esters in kidneys and livers of two patients with Reye's syndrome

An unusual lipid, having an Rf value between that of cholesterol ester and of triglyceride on thin-layer chromatography, was clearly demonstrated in lipids from kidneys and livers of two Japenese children with Reye's syndrome. Gas chromatography-mass spectrometry revealed that the unusual lipid from viscera of the patients was a mixture of fatty acid methyl esters. Whether the occurrence of fatty acid methyl ester is the result of an inborn error of metabolism common to both patients, who were the progeny of consanguineous marriages, or whether it is a common biochemical feature in Reye's syndrome remains the subject of future studies.     

Fatty acid composition of phospholipids in bile in man: promoting effect of deoxycholate on arachidonate

Ninety-five percent of phospholipids (PLs) in bile is secreted as phosphatidylcholine or lecithin. The study of fatty acid patterns of phospholipids present in gallbladder bile could help clarify whether a preponderance of certain fatty acids could play a role in cholesterol gallstone formation in man. In acute bile acid-exchange experiments, it was found that more hydrophobic bile acids did promote the excretion in bile of PL rich in arachidonic acid (a prostaglandin precursor) and stearic acid. We studied, therefore, bile acid, cholesterol and phospholipid fatty acid patterns (measured by gas chromatography) in gallbladder bile, obtained by duodenal intubation and cholecystokinin-stimulation of 24 healthy volunteers with normal liver/gallbladder function (ultrasound). PL-fatty acid composition (mean % +/- SD) was 41.40 (+/- 1.41) for palmitic acid, 2.68 (+/- 0.82) for palmitoleic acid, 5.50 (+/- 1.55) for stearic acid, 12.09 (+/- 0.98) for oleic acid, 32.83 (+/- 3.04) for linoleic acid and 5.64 (+/- 1.59) for arachidonic acid. The proportion of biliary deoxycholate was positively correlated with arachidonic acid (r = 0.71; p less than 0.01), whereas chenodeoxycholate was inversely correlated with arachidonic acid (r = -0.53; p less than 0.01). There was a positive correlation between biliary chenodeoxycholate and linoleic acid (r = 0.48; p less than 0.05) and a negative correlation between biliary deoxycholate and linoleic acid composition (r = 0.68; p less than 0.01). Also a correlation was found between palmitic acid and cholesterol saturation index (r = 0.49; p less than 0.05). We conclude that the hydrophobic bile acid deoxycholate, which does not desaturate cholesterol in bile, promotes the biliary excretion of arachidonic acid. Since arachidonic acid could induce the gallbladder mucosa to produce prostaglandins and mucus, increased biliary PL-arachidonic acid composition might be a factor in cholesterol gallstone disease.