Protein that binds fatty acids (I-FABP)--a new perspective evidence for injury of the small intestine

The article presents literature data on the diagnostic value of the new indicator of the epithelial damage of the small intestine--I-FABP (protein binding fatty acids) and the results of our investigation of this indicator in 63 patients with functional bowel disease, and 20--the control group presented patients with erosive gastritis. Also presented diagnostic value of this indicator and defined the boundaries of normal values for this indicator.     

Myocardial fatty acid oxidation: Evidence for an albumin-receptor-mediated membrane transfer of fatty acids

Summary Using a computer-assisted working rat heart preparation, which allows continuous registration of the respiratory quotient, it was tested which parameters determine fatty acid oxidation in the myocardium.Supplying albumin and palmitate in different concentrations the rate of fatty acid oxidation was measured. The UFA concentrations were calculated using stepwise equilibrium constants. When keeping constant the NEFA/albumin ratio and raising total NEFA concentration, an increase in fatty acid oxidation was found showing a saturation curve. Increasing NEFA at constant albumin concentration, however, results in a linear increase in fatty acid oxidation. Keeping constant the total NEFA concentration elevation of albumin shows an inhibitory effect. These results suggest the existence of a receptor for albumin on heart cell surface, which mediates uptake of albumin-bound NEFA.An additional supply of glucose and lactate does not show any effect on these relations. Acetate and dichloroacetate, an activator of the pyruvate dehydrogenase, are found to be competitive inhibitors of fatty acid oxidation.Supported by the Deutsche Forschungsgemeinschaft, SFB 89-Kardiologie Göttingen     

Effects of saturated and unsaturated fatty acids on estimated desaturase activities during a controlled dietary intervention

Background and aimsDirect measurement of desaturase activities are difficult to obtain in humans. Consequently, surrogate measures of desaturase activity (estimated desaturase activities) have been frequently used in observational studies, and estimated Δ⁹- (or stearoyl-CoA-desaturase (SCD)), Δ⁶- and Δ⁵-desaturase activities have been associated with cardiometabolic disease. Data on how the markers of desaturase activities are modified by changes in dietary fat quality are lacking and therefore warrant examination.Methods and resultsIn a two-period (three weeks) strictly controlled cross-over study, 20 subjects (six women and 14 men) consumed a diet high in saturated fat (SAT-diet) and a rapeseed oil diet (RO-diet), rich in oleic acid (OA), linoleic acid (LA) and α-linolenic acid (ALA). Estimated desaturase activities were calculated as precursor to product FA ratios in serum cholesteryl esters and phospholipids. The estimated SCD [16:1 n-7/16:0] and Δ⁶-desaturase [20:3 n-6/18:2 n-6] was significantly higher while Δ⁵-desaturase [20:4 n-6/20:3 n-6] was significantly lower in the SAT-diet (P < 0.001 for all), compared to the RO-diet. The serum proportions of palmitic, stearic, palmitoleic and dihomo-γ-linolenic acids were significantly higher in the SAT-diet while the proportions of LA and ALA were significantly higher in the RO-diet.ConclusionThis is the first study to demonstrate that surrogate measures of desaturase activities change as a consequence of an alteration in dietary fat quality. Both the [16:1/16:0]-ratio and 16:1 seem to reflect changes in saturated fat intake and may be useful markers of saturated fat intake in Western countries.     

Short chain fatty acids stimulate epithelial mucin 2 expression through differential effects on prostaglandin E(1) and E(2) production by intestinal myofibroblasts

BACKGROUND: The mucus layer protects the gastrointestinal mucosa from mechanical, chemical, and microbial challenge. Mucin 2 (MUC-2) is the most prominent mucin secreted by intestinal epithelial cells. There is accumulating evidence that subepithelial myofibroblasts regulate intestinal epithelial cell function and are an important source of prostaglandins (PG). PG enhance mucin secretion and are key players in mucoprotection. The role of bacterial fermentation products in these processes deserves further attention. AIMS: We therefore determined whether the effect of short chain fatty acids (SCFA) on MUC-2 expression involves intermediate PG production. METHODS: Both mono- and cocultures of epithelial cells and myofibroblasts were used to study the effects of SCFA on MUC-2 expression and PG synthesis. Cell culture supernatants were used to determine the role of myofibroblast derived prostaglandins in increasing MUC-2 expression in epithelial cells. RESULTS: Prostaglandin E(1) (PGE(1)) was found to be far more potent than PGE(2) in stimulating MUC-2 expression. SCFA supported a mucoprotective PG profile, reflected by an increased PGE(1)/PGE(2) ratio in myofibroblast supernatants and increased MUC-2 expression in mono- and cocultures. Incubation with indomethacin revealed the latter to be mediated by PG. CONCLUSIONS: SCFA can differentially regulate PG production, thus stimulating MUC-2 expression in intestinal epithelial cells. This mechanism involving functional interaction between myofibroblasts and epithelial cells may play an important role in the mucoprotective effect of bacterial fermentation products.     

Changes in erythrocyte membrane fatty acids during a clinical trial of eicosapentaenoic acid (EPA) supplementation in schizophrenia

In a previously reported double-blind, placebo-controlled trial of eicosapentaenoic acid (EPA) as supplemental treatment in 40 patients with schizophrenia, we found significant improvement in symptoms as measured by the Positive and Negative Syndrome Scale (PANSS) compared to placebo (Emsley et al. 2002). Here we report changes in fatty acid composition of erythrocyte membranes in the same sample (n = 16 in each group). After 12 weeks of receiving EPA, levels of several saturated and mono-unsaturated fatty acids decreased significantly while levels of n-3 fatty acids increased significantly compared to the placebo group. Increases of n-3 and n-6 fatty acids in the erythrocyte membranes were greater in subjects who improved more than 20% on overall symptoms. Changes in fatty acids correlated significantly with improvement in PANSS sub-scale scores, more so in females than in males. Docosahexaenoic acid (DHA) (22:6n-3) levels increased less than expected, suggesting a possible defect in synthesis or incorporation of DHA into membranes in schizophrenia. Improvement in dyskinesia correlated significantly with an increase in alpha-linolenic acid (18:3n-3; p = 0.03), and a decrease in 20:1n-9 (p = 0.005).     

Deficiency of essential fatty acids and membrane fluidity during pregnancy and lactation.

In a group of 19 normal pregnant women, plasma lipids were extracted, phospholipids were isolated, and the fatty acid (FA) compositions were measured by capillary gas chromatography. Blood samples were taken at 36 wk, at labor, and at 6 wk postpartum. The FA profiles showed deficiencies of omega 6 and omega 3 FA (omega indicating the length of the terminal saturated chain), the latter more severe, at all three times. Mean melting point (MMP) was calculated for each sample as an index of "fluidity" based upon all FA present. MMP varied linearly with total polyunsaturated FA and with double bond index, current measures of "fluidity" and essential FA status. MMP was elevated 9-11 degrees C in plasma phospholipids of women during pregnancy and labor and postpartum. Lactating mothers showed less recovery from the deficiencies than did the nonlactating mothers, but neither approached normal at 6 wk. The changes seen in phospholipid profiles suggest a significant transfer of omega 3 and omega 6 polyunsaturated FA from the mother to the fetus. These FA are essential for normal fetal growth and development; their relative deficiency in maternal circulation suggests that dietary supplementation may be indicated.     

Assay of plasmalogens and polyunsaturated fatty acids (PUFA) in erythrocytes and fibroblasts

The direct transesterification method of Lepage and Roy is described as used in our laboratory for the analysis of plasmalogens and polyunsaturated fatty acids in erythrocytes and cultured fibroblasts by gas chromatography. An overview is given of the plasmalogen ratios and docosahexaenoic acid concentrations from controls and patients with different peroxisomal disorders investigated in our laboratory.     

Apolipoprotein E enrichment of immuno-separated chylomicron and chylomicron remnants following saturated fatty acids

AimWe examined the effect of meal fatty acids on lipid and apolipoprotein concentrations of very low density lipoprotein (VLDL) and chylomicron/chylomicron remnants in lipid fractions with a Svedberg flotation rate (S_f) 60–400 and S_f 20–60.Methods and resultsSix healthy middle-aged men received in random order mixed meals enriched with saturated (SFA), polyunsaturated (PUFA) or monounsaturated (MUFA) fatty acids on 3 occasions. VLDL and chylomicron/chylomicron remnants in the lipid fractions were separated by immunoaffinity chromatography against apo B-100. In the S_f 60–400 chylomicron/chylomicron remnants, triacylglycerol and cholesterol concentrations were significantly lower following PUFA compared with SFA and MUFA (P ≤ 0.05). Apolipoprotein (apo) E responses were significantly higher after SFA in chylomicron/chylomicron remnants and VLDL compared with PUFA and MUFA (P < 0.007). However, apo B responses (particle number) were higher following MUFA than SFA (P = 0.039 for chylomicron/chylomicron remnants). Composition of the chylomicron/chylomicron remnants (expressed per particle) revealed differences in their triacylglycerol and apo E contents; in the S_f 60–400 fraction, SFA-rich chylomicron/chylomicron remnants contained significantly more triacylglycerol than MUFA (P = 0.028), more apo E than PUFA- and MUFA-rich particles (P < 0.05) and in the S_f 20–60 fraction, more apo E than MUFA (P = 0.009).ConclusionThere are specific differences in the composition of chylomicron/chylomicron remnants formed after saturated compared with unsaturated fatty acid-rich meals which could determine their metabolic fate in the circulation and subsequent atherogenicity.     

Adrenocorticotropin(1-10) and -(11-24) promote adrenal steroidogenesis by different mechanisms

ACTH1-10 and ACTH11-24 each elicit cortisol secretion submaximally in freshly dispersed or cultured beef adrenal cortical cells. The combination of ACTH1-10 and ACTH11-24 promotes cortisol release to the maximal level elicited by ACTH1-24. Maximal cortisol release by ACTH11-24, but not by ACTH1-24 or ACTH1-10, was enhanced by forskolin. The calcium channel blockers nifedipine and verapamil inhibited cortisol release by ACTH1-10, ACTH1-24 or ACTH11-24, suggesting calcium influx to be essential for steroid secretion regardless of the secretagogue. Vanadium, in a dose-dependent manner, inhibited cortisol secretion elicited by ACTH1-24 and ACTH1-10 but not that caused by ACTH11-24. These results suggest that there are at least two receptors mediating ACTH1-24-dependent steroid secretion. One class of receptor recognizes ACTH1-10 but not ACTH11-24 and is linked to the cAMP messenger pathway.     

IgM myeloma: a rare entity characterized by a CD20-CD56-CD117- immunophenotype and the t(11;14)

IgM myeloma is a very rare and poorly defined entity. In a detailed assessment of 10 cases, it was demonstrated that 70% had an aberrant phenotype based on the expression of CD19, CD45, CD27 and Cyclin D1 but all cases lacked CD56 and CD117. Interphase fluorescence in situ hybridization demonstrated deletion 13 in 50% while 5/8 cases assessed had a t(11;14). Despite the high incidence of the t(11;14), CD20 was only expressed in one of nine cases. We conclude that IgM myeloma is a distinctive subset characterized by a CD20-CD56-CD117- phenotype and the t(11;14).     

Gene expression profiling in skeletal muscle of Zucker diabetic fatty rats: implications for a role of stearoyl-CoA desaturase 1 in insulin resistance

Aims/hypothesis Insulin resistance in skeletal muscle is a hallmark of type 2 diabetes. Therefore, we sought to identify and validate genes involved in the development of insulin resistance in skeletal muscle. Materials Differentially regulated genes in skeletal muscle of male obese insulin-resistant, and lean insulin-sensitive Zucker diabetic fatty (ZDF) rats were determined using Affymetrix microarrays. Based on these data, various aspects of glucose disposal, insulin signalling and fatty acid composition were analysed in a muscle cell line overexpressing stearoyl-CoA desaturase 1 (SCD1). Results Gene expression profiling in insulin-resistant skeletal muscle revealed the most pronounced changes in gene expression for genes involved in lipid metabolism. Among these, Scd1 showed increased expression in insulin-resistant animals, correlating with increased amounts of palmitoleoyl-CoA. This was further investigated in a muscle cell line that overexpressed SCD1 and accumulated lipids, revealing impairments of glucose uptake and of different steps of the insulin signalling cascade. We also observed differential effects of high-glucose and fatty acid treatment on glucose uptake and long-chain fatty acyl-CoA profiles, and in particular an accumulation of palmitoleoyl-CoA in cells overexpressing SCD1. Conclusions/interpretation Insulin-resistant skeletal muscle of ZDF rats is characterised by a specific gene expression profile with increased levels of Scd1. An insulin-resistant phenotype similar to that obtained by treatment with palmitate and high glucose can be induced in vitro by overexpression of SCD1 in muscle cells. This supports the hypothesis that elevated SCD1 expression is a possible cause of insulin resistance and type 2 diabetes. Electronic supplementary material Supplementary material is available for this article at and accessible for authorised users.     

Enhanced activity in parathyroid hormone-(1-14) and -(1-11): novel peptides for probing ligand-receptor interactions.

The amino-terminal portion of PTH is critical for PTH-1 receptor (P1Rc) activation. In exploring this component of the ligand receptor interaction, we recently showed that the agonist potency of the weakly active PTH-(1-14)NH(2) peptide can be enhanced by natural amino acid substitutions at several positions, including position 11 (normally leucine). Here we show that the potency of PTH-(1-14)NH(2) can be enhanced by using nonnatural amino acids that increase the length and polarizability of the position 11 side-chain. Thus, in LLC-PK(1) cells stably expressing high levels of the human P1Rc, [homoarginine([Har)(11)]PTH-(1-14)NH(2) was 30-fold more potent for cAMP production than was native PTH-(1-14)NH(2). Combining the homoarginine-11 substitution with other recently identified activity-enhancing substitutions yielded [Ala(3,12),Gln(10),Har(11),Trp(14)]PTH-(1-14)NH(2), which was 1500-fold more potent than PTH-(1-14)NH(2) (EC(50) = 0.12 +/- 0.04 and 190 +/- 20 microM, respectively) and only 63-fold less potent than PTH-(1-34) (EC(50) = 1.9 +/- 0.5 nM). The even shorter analog [Ala(3),Gln(10),Har(11)]PTH-(1-11)NH(2) was also a full cAMP agonist (EC(50) = 3.1 +/- 1.5 microM). Receptor mutations at Phe(184) and Leu(187) located near the boundary of the amino-terminal domain and transmembrane domain-1 severely impaired responsiveness to the PTH-(1-11) analog. Overall, these studies demonstrate that PTH analogs of only 11 amino acids are sufficient for activation of the PTH-1 receptor through interaction with its juxtamembrane region.     

Spectral Characteristics and Molecular Structure of (E)-1-(4-Chlorophenyl)-3-(4-(Dimethylamino)Phenyl)Prop-2-en-1-One (DAP)

In this work, a laser dye of (E)-1-(4-chlorophenyl)-3-(4-(dimethylamino)phenyl)prop-2-en-1-one (DAP) was synthesized and examined as a new laser medium. The compound DAP’s photophysical properties were investigated under the influence of solvents, concentrations, and pump power excitations. The absorption spectra showed a single band, and the shape of the spectra remained the same, regardless of the optical density. The fluorescence spectra showed a band around 538 nm; its intensity was inversely proportional to the concentration. DAP exhibits dual amplified spontaneous emission (ASE) bands at 545 and 565 nm under suitable pump power laser excitation and concentration. The results revealed that the ASE band at 565 nm is affected by solvents polarity, concentrations and pump power energies. This band could be attributed to the combination of two excited molecules and the solvent between them (superexciplex). Moreover, the molecular structure, the energy bandgap, and the total energy of DAP was calculated using density functional theory.     

Examination of cardiovascular parameters and plasma free fatty acids during esophago-gastro-duodenoscopy (author's transl)

53 patients were examined for changes of blood pressure, heart rate, ECG and plasma free fatty acids during esophago-gastro-duodenoscopy. In 23 cases there were premature contractions, occuring in small numbers only in most of the cases. Only in 5 cases there was an accumulation of premature contractions and in one case ventricular bigeminism occurred. The maximum of premature beats was observed when the primarily sitting patient was put into supine position. In 7 patients there was a lowering of the ST-segment in the ECG by at least 0.1 mV, mostly in patients who already had an abnormal ST-segment before endoscopy. The pulse rate went up by an average of 50.1 per cent, the systolic blood pressure by 14 and the diastolic blood pressure by 17 per cent. The increase of plasma free fatty acids in the total patient material was not statistically significant, but patients with a deterioration of ECG-findings endoscopy had a significantly higher increase of plasma free fatty acids. There was a tendency towards a positive correlation between the number of premature beats and the increase of plasma free fatty acids. It cannot be decided from our study whether the mobilization of free fatty acids is causing the above observed increase of premature beats or whether both phenomena are merely a result of sympathetic nervous stimulation. Gastric fiberoscopy may be applied to elderly patients with decreased cardiac function. The endoscopic procedure should not be started on the sitting patient but primarily in left supine position.