linoleic-acid and Acute-Disease

Dietary fat has been suggested to determine the therapeutic effect of enteral diets in Crohn's disease.. To assess the efficacy of two whole protein based diets with different fat compositions (n6 polyunsaturated fatty acids v monounsaturated fatty acids) in inducing clinical remission in active Crohn's disease compared with steroids.. Sixty two patients with active Crohn's disease were randomised to receive, for not more than 4 weeks: (a) a polymeric enteral diet containing 35 g of lipids per 1000 kcal, high in oleate (79%) and low in linoleate (6.5%) (PEN1), (b) an identical enteral diet except for the type of fat which was high in linoleate (45%) and low in oleate (28%) (PEN2), or (c) oral prednisone (1 mg/kg/day). Diets were double blindly administered. The steroid group received a conventional ward diet. Treatment failure was considered when remission was not achieved at week 4. Clinical activity and biological and nutritional parameters were monitored. Independent predictors of remission were identified by stepwise logistic regression analysis.. Overall remission rates (by intention to treat) were 20% (4/20) for PEN1, 52% (12/23) for PEN2, and 79% (15/19) for steroids (overall p=0.001; p<0.0005 steroids v PEN1, and p=0.056 PEN2 v PEN1). After excluding those patients who were non-compliant during the first week (per protocol analysis), remission rates were 27%, 63%, and 79%, respectively (p=0.008, steroids and PEN2 v PEN1). After adjusting for confounding variables, PEN1 remained significantly associated with a poor response.. The type of dietary fat may be of importance for the primary therapeutic effect of enteral nutrition in active Crohn's disease.

Topics: Acute Disease; Adolescent; Adult; Crohn Disease; Dietary Fats; Double-Blind Method; Enteral Nutrition; Europe; Female; Food, Formulated; Glucocorticoids; Humans; Linoleic Acid; Male; Middle Aged; Oleic Acid; Regression Analysis

Topics: Acute Disease; Administration, Topical; Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Body Water; Budesonide; Dermatitis, Irritant; Drug Administration Schedule; Humans; Linoleic Acid; Linoleic Acids; Methylprednisolone; Pregnenediones; Skin

Pancreatic oxidative stress with depletion of pancreatic glutathione is an early feature in all tested models of acute pancreatitis, and sooner or later the problem extends to the lung, irrespective of disease severity, whether toward spontaneous recovery or death from multisystem organ failure. We, therefore, sought evidence of oxidative stress in the human disease by analyzing admission blood samples. We found it from high concentrations of oxidatively altered linoleic acid in serum and vitamin C in plasma (p < 0.001 vs controls or a group of other acute abdominal crises where the proportion of patients with admission Apache II scores < or > 8 was similar). These changes were accompanied by subnormal levels of ascorbic acid in plasma (p < 0.001); selenium (p < 0.001), beta-carotene (p < 0.001), and alpha-tocopherol in serum (p = 0.005 for its molar ratio to cholesterol). Paradoxically, the plasma concentration of S-adenosylmethionine was elevated (p = 0.02), suggesting that this proximate bioactive metabolite of the essential amino acid had backtracked because its intracellular metabolism down the methionine trans-sulfuration pathway toward glutathione synthesis was disrupted. The aberrations transcended putative etiological factor, duration of symptoms, or disease severity. We conclude: (1) that oxidative stress has pervaded the vascular compartment by the time of admission in patients with acute pancreatitis, and, (2) that blood micronutrient antioxidant profiles at this stage are consistent not only with compromised intracellular capacity to synthesize/refurbish glutathione, but also vulnerability of intra- and extracellular lipid targets.

Topics: Acetylcysteine; Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Antioxidants; Discriminant Analysis; Free Radical Scavengers; Humans; Linoleic Acid; Linoleic Acids; Middle Aged; Oxidative Stress; Pancreatitis; S-Adenosylmethionine

The usefulness of micronutrient antioxidant therapy for recurrent (non-gallstone) pancreatitis has recently been endorsed by a 20-week double-blind double-dummy cross-over trial in 20 patients. Treatment was delivered as two types of tablets, providing daily doses of 600 micrograms organic selenium, 9000 i.u. beta-carotene, 0.54 g vitamin C, 270 i.u. vitamin E and 2 g methionine. We report antioxidant profiles in blood samples collected before entry, at the cross-over stage and upon completion of trial. Baseline serum concentrations of selenium, beta-carotene and vitamin E in the patients were significantly lower than in healthy controls, were unaltered by placebo and normalized by active treatment, but reverted to basal values in the subgroup that received placebo subsequently. The baseline serum concentration of a free radical marker--the 9-cis, 11-trans isomer of linoleic acid--was significantly higher in the patients than in controls, fell inexplicably in the placebo phase and fell further upon active treatment. Discriminant analysis eliminated the overlap in free radical marker and selenium concentrations between control sera on the one hand and baseline or post-placebo samples from the patients on the other: antioxidant treatment normalized the relationship between these biochemical parameters. Subnormal baseline serum levels of S-adenosylmethionine drifted downwards upon active treatment whereas a sharp rise was noted when a relapse of pancreatitis occurred during the placebo phase. The results confirm that adequate exposure to antioxidants in the active treatment phase was associated with amelioration of oxidative stress, and that there was no residual effect 10 weeks after switching over to placebo treatment. Furthermore, the paradoxical behaviour of S-adenosylmethionine may imply that the beneficial effect of micronutrient antioxidants in recurrent pancreatitis is linked with preservation of the methionine trans-sulfuration pathway in pancreatic acinar cells.

Topics: Acute Disease; Adolescent; Adult; Aged; Antioxidants; Chronic Disease; Double-Blind Method; Female; Free Radicals; Glutathione Peroxidase; Humans; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Pancreatitis; S-Adenosylmethionine; Selenium

Total and individual plasma free fatty acids (FFA) were measured on admission and over the next 4 days in 24 patients admitted to the hospital with chest pain and suspected acute myocardial infarction (AMI). In a prospective randomized fashion, the patients were either given an infusion of 300 gm of glucose, 50 units of insulin, and 80 mEq of KCl per liter at a rate of 1.5 ml/kg/hr over the initial 48 hours of hospitalization, or they served as controls receiving conventional therapy. Eleven patients were in the control group and 13 were in the glucose-insulin-potassium (G-I-K) group. Twenty-one of the patients had an AMI by CK-MB rise and ECG changes (in the G-I-K group three did not evolve AMI). The total plasma FFA were 840 +/- 134 microM/L in the controls and 933 +/- 160 microM/L in the G-I-K group initially (prestudy). Total FFA rapidly fell in the G-I-K group and then rebounded when G-I-K was stopped. In contrast, total FFA values fell gradually in the control group over the 4-day period. The individual FFA had similar percentages initially in the two groups. In the control group the percent of individual plasma FFA was unchanged over the period studied, although there was some mild random day-to-day fluctuation. In contrast in the G-I-K group linoleic acid fell both during and after the infusion was stopped (26.8% to 19.1% P less than 0.001). Arachidonic acid doubled in percentage of the total FFA value during G-I-K infusion (3.1% to 6.5%, P less than 0.002) and returned to the control value when it was stopped. Thus G-I-K infusion during AMI reduces the total level of plasma FFA while increasing the percent of arachidonic and decreasing the percent of linoleic acid, observations proposed to reflect improved membrane stability of the ischemic myocardium.

Topics: Acute Disease; Adult; Aged; Arachidonic Acid; Arachidonic Acids; Clinical Trials as Topic; Fatty Acids, Nonesterified; Female; Glucose; Humans; Infusions, Parenteral; Insulin; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Myocardial Infarction; Potassium; Prospective Studies; Random Allocation

Dynamic changes in metabolites may affect liver disease progression, and provide new methods for predicting liver damage. We used ultra-performance liquid chromatography-mass spectroscopy to assess serum metabolites in healthy controls (HC), and patients with acute hepatitis E (AHE) or hepatitis E virus acute liver failure (HEV-ALF). The principal component analysis, partial least squares discriminant analysis, and discriminant analysis of orthogonal projections to latent structures models illustrated significant differences in the metabolite components between AHE patients and HCs, or between HEV-ALF and AHE patients. In pathway enrichment analysis, we further identified two altered pathways, including linoleic acid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis, when comparing AHE patients with HCs. Linoleic acid metabolism and porphyrin and chlorophyll metabolism pathways were significantly different in HEV-ALF when compared with AHE patients. The discriminative performances of differential metabolites showed that taurocholic acid, glycocholic acid, glycochenodeoxycholate-3-sulfate, and docosahexaenoic acid could be used to distinguish HEV-ALF from AHE patients. The serum levels of glycocholic acid, taurocholic acid, deoxycholic acid glycine conjugate, and docosahexaenoic acid were associated with the prognosis of HEV-ALF patients. Dynamic changes in serum metabolites were associated with AHE infection and severity. The identified metabolites can be used to diagnose and predict the prognosis of HEV-ALF.

Topics: Acute Disease; Docosahexaenoic Acids; Glycocholic Acid; Hepatitis E; Hepatitis E virus; Humans; Linoleic Acid; Taurocholic Acid

Coliform mastitis is a severe and sometimes fatal disease characterized by an unregulated inflammatory response. The initiation, progression, and resolution of inflammatory responses are regulated, in part, by potent oxylipid metabolites derived from polyunsaturated fatty acids. The purpose of this study was to characterize the biosynthesis and diversity of oxylipid metabolites during acute bovine coliform mastitis. Eleven cows diagnosed with naturally occurring acute systemic coliform mastitis and 13 healthy control cows, matched for lactation number and days in milk, were selected for comparison of oxylipid and free fatty acid concentrations in both milk and plasma. Oxylipids and free fatty acids were quantified using liquid chromatography-tandem mass spectrometry. All polyunsaturated fatty acids quantified in milk were elevated during coliform mastitis with linoleic acid being the most abundant. Oxylipids synthesized through the lipoxygenase and cytochrome P450 pathways accounted for the majority of the oxylipid biosynthesis. This study demonstrated a complex and diverse oxylipid network, most pronounced at the level of the mammary gland. Substrate availability, biosynthetic pathways, and degree of metabolism influence the biosynthesis of oxylipids during bovine coliform mastitis. Further studies are required to identify targets for novel interventions that modulate oxylipid biosynthesis during coliform mastitis to optimize inflammation.

Topics: Acute Disease; Animals; Case-Control Studies; Cattle; Chromatography, Liquid; Escherichia coli Infections; Fatty Acids, Nonesterified; Fatty Acids, Unsaturated; Female; Linoleic Acid; Lipid Metabolism; Mammary Glands, Animal; Mastitis, Bovine; Milk; Tandem Mass Spectrometry

To evaluate the generation of halogenated fatty acids in the areas of fat necrosis during acute pancreatitis and to evaluate the effects of these molecules on the ensuing inflammatory process.. Lipid mediators derived from adipose tissue have been implicated in the progression of acute pancreatitis, although their precise role remains unknown.. Acute pancreatitis was induced in rats by intraductal infusion of 3.5% sodium taurocholate. Fatty acid chlorohydrins (FA-Cl) were measured in adipose tissue, ascitic fluid, and plasma by mass spectrometry. Chlorohydrins were also instilled in the rats' peritoneal cavity, and their effects on peritoneal macrophages activation and in systemic inflammation were evaluated. Finally, they have also been measured in plasma from human patients with acute pancreatitis.. Induced acute pancreatitis results in a substantial release not only of free fatty acids but also of the chlorohydrins of both oleic and linoleic acids from adipose tissue. In plasma, only the chlorohydrin of oleic acid was detected. Administration of 250-μM lipid chlorohydrins, which is the concentration found in ascitic fluid, induces the expression of TNFα and interleukin-1β in peritoneal macrophages and increases the systemic inflammatory response in pancreatitis. Finally, increased concentrations of oleic acid chlorohydrin have been found in plasma of human patients with pancreatitis.. During acute pancreatitis, adipose tissue release FA-Cl, which exacerbate the systemic inflammatory response.

Topics: Acute Disease; Animals; Biomarkers; Case-Control Studies; Chlorohydrins; Cholagogues and Choleretics; Chromatography, Liquid; Fat Necrosis; Gas Chromatography-Mass Spectrometry; Humans; Inflammation; Linoleic Acid; Macrophage Activation; Male; Mass Spectrometry; Oleic Acid; Pancreatitis; Peroxidase; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Taurocholic Acid

In the Long-Evans Cinnamon rat, copper accumulates in the liver because of a mutation in the copper-transporting ATPase gene, and peroxidative stresses are supposed to be augmented. We examined the effects of dietary fatty acids on hepatitis, hepatic gene expression, and survival. Rats were fed a conventional, low-fat diet (CE2), a CE2 diet supplemented with 10 wt% of lard (Lar), high-linoleic soybean oil (Soy), or a mixture of docosahexaenoic acid (DHA)-rich fish oil and soybean oil (DHA/Soy). Among female rats, the mean survival times of the DHA/Soy and the Soy groups were longer by 17 approximately 20% than in the Lar and the CE2 groups. Among male rats, the survival times were much longer than in the females, but no significant difference in survival was observed among the dietary groups. Serum ceruloplasmin levels in female and male rats of all of the dietary groups were similar. Serum transaminase levels of the DHA/Soy group tended to be lower than in the CE2 group. Histological examinations revealed a marked degeneration in hepatic tissue integrity in the Lar and CE2 groups but not in the DHA/Soy group. Hepatic levels of metal-related genes, transferrin and ceruloplasmin, as well as those related to bile acid synthesis were up-regulated, and an inflammation-related gene (cyclooxygenase [COX]-2) was down-regulated in the DHA/Soy group. Some proliferation-related genes were also affected by the dietary fatty acids. These results indicate that polyunsaturated fatty acids suppress the development of acute hepatitis and prolong survival in females, regardless of whether they are of the n-6 or n-3 type, which are associated with altered gene expressions.

Topics: Acute Disease; Animals; Cyclooxygenase 1; Cyclooxygenase 2; Dietary Fats, Unsaturated; Disease Models, Animal; Docosahexaenoic Acids; Fatty Acids; Fatty Acids, Unsaturated; Female; Fish Oils; Gene Expression; Hepatitis; Hepatolenticular Degeneration; Isoenzymes; Linoleic Acid; Liver; Male; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Inbred LEC; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Soybean Oil; Survival Rate

A number of acute wasting conditions are associated with an upregulation of the ubiquitin-proteasome system in skeletal muscle. Eicosapentaenoic acid (EPA) is effective in attenuating the increased protein catabolism in muscle in cancer cachexia, possibly due to inhibition of 15-hydroxyeicosatetraenoic acid (15-HETE) formation. To determine if a similar pathway is involved in other catabolic conditions, the effect of EPA on muscle protein degradation and activation of the ubiquitin-proteasome pathway has been determined during acute fasting in mice. When compared with a vehicle control group (olive oil) there was a significant decrease in proteolysis of the soleus muscles of mice treated with EPA after starvation for 24 h, together with an attenuation of the proteasome "chymotryptic-like" enzyme activity and the induction of the expression of the 20S proteasome alpha-subunits, the 19S regulator and p42, an ATPase subunit of the 19S regulator in gastrocnemius muscle, and the ubiquitin-conjugating enzyme E2(14k). The effect was not shown with the related (n-3) fatty acid docosahexaenoic acid (DHA) or with linoleic acid. However, 2,3,5-trimethyl-6-(3-pyridylmethyl)1,4-benzoquinone (CV-6504), an inhibitor of 5-, 12- and 15-lipoxygenases also attenuated muscle protein catabolism, proteasome "chymotryptic-like" enzyme activity and expression of proteasome 20S alpha-subunits in soleus muscles from acute fasted mice. These results suggest that protein catabolism in starvation and cancer cachexia is mediated through a common pathway, which is inhibited by EPA and is likely to involve a lipoxygenase metabolite as a signal transducer.

Topics: Acute Disease; Adenosine Triphosphatases; Administration, Oral; Animals; Benzoquinones; Cysteine Endopeptidases; Docosahexaenoic Acids; Eicosapentaenoic Acid; Endopeptidases; Enzyme Activation; Female; In Vitro Techniques; Linoleic Acid; Lipoxygenase Inhibitors; Mice; Mice, Inbred Strains; Multienzyme Complexes; Muscle, Skeletal; Proteasome Endopeptidase Complex; Signal Transduction; Starvation; Ubiquitins

In acute liver failure the liver has to regenerate, which may increase the consumption of essential fatty acids. Nutritional support consists mainly of infusion of glucose. It is therefore possible that essential fatty acid deficiency may develop in such patients.. Plasma phospholipid composition was studied in healthy controls (n=11), in patients with acute liver failure, (n=10), in patients with stable cirrhosis (n=7), and in patients with acute on chronic liver disease with hepatic encephalopathy (n=6). The influence of 2 days of fat-free diet followed by infusion of glucose was studied in five healthy controls.. The ratio between the sums of nonessential/ essential fatty acids, (n-7+n-9)/(n-3+n-6), was higher in patients with acute liver failure (0.73+/-0.17) compared to healthy controls (0.35+/-0.06, p<0.001). The ratio was also higher in patients with acute on chronic liver disease (1.11+/-0.39) compared to patients with cirrhosis (0.61+/-0.18, p<0.01). These differences were mainly due to low levels of linoleic acid and high levels of oleic acid in the patients with acute liver failure and acute on chronic liver disease. Two days of fat-free diet followed by infusion of glucose did not change this ratio (0.40+/-0.04 vs. 0.47+/-0.05, NS) in healthy controls. The essential fatty acid deficiency indicator eicosatrienoic acid was detectable in 2 out of 11 controls, in 5/10 with acute liver failure, in 7/7 with cirrhosis, and in 6/7 with acute on chronic liver disease.. Acute severe deterioration of liver function was associated with changes in the fatty acid composition of plasma phospholipids suggestive of essential fatty acid deficiency.

Topics: Acute Disease; Adult; Chronic Disease; Dietary Fats; Fatty Acids; Female; Glucose; Hepatic Encephalopathy; Humans; Linoleic Acid; Liver Cirrhosis; Liver Diseases; Liver Failure; Male; Middle Aged; Oleic Acid; Phospholipids; Reference Values

High concentrations of lipid peroxidation (free-radical oxidation) products have been found in bile from patients with recurrent pancreatitis, and the principal component, after hydrolysis, has been identified as an isomerised form of linoleic acid -- typical concentration 25 mmol/l, compared with 4 mmol/l in controls. Chromatographically identical products can be generated by peroxidising linoleic acid using an ultraviolet (UV) source in the presence of albumin, whereas peroxidation by lipoxidase without albumin results in a constellation of products that bear no resemblance to those in biological fluids. These facts, and the suspicion that reflux of abnormal bile may be an initiating mechanism in acute pancreatitis, led us to investigate the effects of linoleic acid peroxidation products in the rat pancreas. Two concentrations of ultraviolet-peroxidised linoleic acid were used (3.6 mmol/l or 25 mmol/l, in a 2.09% solution of bile salts containing albumin 10 g/l) to simulate the human findings and, for comparison, the effects of lipoxidase-peroxidised linoleic acid, 25 mmol/l (in the 2.09% bile salt solution but without albumin), were also studied. 100 microliter of test solution was infused retrogradely into the pancreatic duct using a syringe pump. The results were assessed microscopically at 3-h intervals, and histologically at 12 h: if the animal died before the end of the experiment, the time of death was recorded. Both forms of peroxidised linoleic acid, 25 mmol/l, caused a greater degree of pancreatic injury than that produced by bile salts alone (e.g., macroscopic score at 3 h: ultraviolet, P less than 0.001; lipoxidase, P less than 0.05). Non-peroxidised linoleic acid 25 mmol/l caused less damage than ultraviolet-peroxidised linoleic acid 25 mmol/l, both macroscopically (3 h: P less than 0.01; 12 h: P less than 0.05) and on histology (P less than 0.01). Pancreatic haemorrhage was not a feature.

Topics: Acute Disease; Animals; Bile Acids and Salts; Linoleic Acid; Linoleic Acids; Lipid Peroxides; Male; Oxidoreductases; Pancreas; Pancreatitis; Rats; Rats, Inbred Strains; Ultraviolet Rays

Although accurate epidemiological data is not available, it is generally agreed that acute lithium toxicity is becoming a more frequent problem. Consequently recognition and treatment of lithium toxicity has also become more important. Acute lithium toxicity is generally subdivided into three grades: mild, moderate, and severe. Mild toxicity can often be managed successfully with minimal intervention; often only cessation or reduction of lithium doses is sufficient. Moderate and severe toxicity both require more aggressive approaches. Initial general anti-poisoning measures, such as gastric lavage, may be helpful, but the ultimate success of treatment depends upon the elimination of lithium from the body. Hemodialysis, and, to a lesser extent, peritoneal dialysis, will both rapidly eliminate lithium from the body. Sodium administration, and the maintenance of high-normal sodium levels, may also reduce the severity of lithium toxicity by removing the dangerous intracellular fraction of lithium from inside excitable cells.

Topics: Acute Disease; Humans; Linoleic Acid; Linoleic Acids; Lithium; Renal Dialysis; Sodium