Assessment of Plasma Phospholipid Very-Long-Chain Saturated Fatty Acid Levels and Healthy Aging.

Importance: Identifying novel factors that protect against age-related diseases and promote healthy aging is critical to public health. Higher levels of circulating very-long-chain saturated fatty acids (VLSFAs) are integrated biomarkers of diet and metabolism shown to have beneficial associations in cardiovascular disease and total mortality, but whether they are associated with overall healthy aging is unknown. Objective: To examine the association of circulating levels of 3 VLSFAs with unhealthy aging events, including incident chronic disease (cardiovascular disease, cancer, lung disease or severe kidney disease), physical dysfunction, and cognitive decline. Design, Setting, and Participants: This cohort study used 1992 to 2014 data from the Cardiovascular Health Study (CHS). The CHS is a multicenter, population-based study of cardiovascular disease among older adults. Among the 4559 CHS participants with available fatty acid data, 1879 participants who had an age-related event before their first measurement were excluded. Data analysis was performed in 2020. Main Outcomes and Measures: Plasma phospholipid VLSFA levels were measured by thin-layer chromatography followed by gas chromatography. The main outcome was the hazard ratio (HR) of an incident unhealthy aging event associated with serial measures of plasma arachidic acid, behenic acid, and lignoceric acid. Results: Among the 2680 study participants (976 men [36.4%]), the mean (SD) age was 74.7 (4.8) years old at entry. During a median (interquartile range) of 6.4 (2.9-12.9) years of follow-up, 2484 participants experienced an unhealthy event. Compared with the lowest quintile, levels of behenic acid in the highest quintile of the fatty acid distribution were associated with 15% lower risk of an unhealthy event (HR, 0.85; 95% CI, 0.74-0.97; P for trend = .01) after adjustment for demographic characteristics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of lignoceric acid were similarly associated with 16% lower risk of an unhealthy event (HR, 0.84; 95% CI, 0.73-0.95; P for trend = .001). Conclusions and Relevance: These findings suggest that higher levels of circulating behenic acid and lignoceric acid are associated with lower risk of unhealthy aging events. These results highlight the need to explore determinants of circulating VLSFAs for potential novel efforts to promote healthy aging.

Prediction of Residual Risk by Ceramide-Phospholipid Score in Patients With Stable Coronary Heart Disease on Optimal Medical Therapy.

Background Identification of patients with stable coronary heart disease who are at significant residual risk could be helpful for targeted prevention. Our aim was to determine the prognostic value of the recently introduced ceramide- and phospholipid-based risk score, the Cardiovascular Event Risk Test (CERT2), in patients with stable coronary heart disease on optimal medical therapy and to identify biological processes that contribute to the CERT2 score. Methods and Results Plasma samples (n=11 222) obtained from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial were analyzed using a tandem liquid chromatography-mass spectrometry method. STABILITY was a trial in patients with stable coronary heart disease randomized to the lipoprotein-associated phospholipase A2 inhibitor darapladib or placebo on optimized medical therapy at baseline, with a median follow-up of 3.7 years. Hazard ratios per SD for the CERT2 risk score were 1.32 (95% CI, 1.25-1.39) for major adverse cardiovascular event, 1.47 (95% CI, 1.35-1.59) for cardiovascular death, 1.32 (95% CI, 1.16-1.49) for stroke, 1.23 (95% CI, 1.14-1.33) for myocardial infarction, and 1.56 (95% CI, 1.39-1.76) for hospitalization due to heart failure, when adjusted for traditional cardiovascular risk factors. CERT2 showed correlation (P<0.001, r>0.2) with inflammatory markers high-sensitivity C-reactive protein, interleukin 6, the heart failure marker N-terminal pro-B-type natriuretic peptide, and low-density lipoprotein cholesterol. After also adjusting for levels of other prognostic biomarkers, the CERT2 score was still independently related to the risk of cardiovascular death but not to nonfatal events. Conclusions The CERT2 risk score can detect residual risk in patients with stable coronary heart disease and is associated with biomarkers indicating inflammation, myocardial necrosis, myocardial dysfunction, renal dysfunction, and dyslipidemia. REGISTRATION URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT00799903.

Oxidative stress assessment in sickle cell anemia patients treated with hydroxyurea.

Hydroxyurea (HU) is used as a therapy in sickle cell anemia (SCA). Many studies have established that HU improves patient quality of life by reducing symptoms. However, the effect of HU on erythrocytes is not well-described. We evaluated several parameters related to oxidative stress and total lipid content of erythrocytes in patients with SCA. The patient cohort consisted of 7 SCA patients treated with HU, 17 untreated SCA patients, and 15 healthy subjects. Erythrocytes from patients with SCA displayed increased oxidative stress relative to the control group, including higher thiobarbituric acid reactive substances (TBARS), Fe3+ content, and osmotic fragility, and decreased total cholesterol. We observed that treatment of SCA patients with HU increased Fe3+ content and activity of glutathione peroxidase, and decreased glutathione reductase activity, glutathione levels, total cholesterol, and phospholipid content comaperaded to patients untreated with HU. Thus, HU alters biochemical characteristics of erythrocytes; future studies will determine whether they are beneficial or not.

Liposomes as potential masking agents in sport doping. Part 1: analysis of phospholipids and sphingomyelins in drugs and biological fluids by aqueous normal-phase liquid chromatography-tandem mass spectrometry.

In the present work, aqueous normal-phase liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), in different acquisition modes, was employed for the direct analysis and profiling of nine phospholipid classes (phosphatidic acids, phosphatidylserines, phosphatidylethanolamines, lysophosphatidylethanolamines, phosphatidylglycerols, phosphatidylinositols, phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins) in biological and pharmaceutical matrices. After chromatographic separation by a diol column, detection and elucidation of phospholipid and sphingomyelin classes and molecular species were performed by different scan acquisition modes. For screening analysis, molecular ions [M + H]+ were detected in positive precursor ion scan of m/z 184 for the classes of phosphatidylcholines, lyso-phosphatidylcholines and sphingomyelins; while phosphatidylethanolamines and lyso-phosphatidylethanolamines were detected monitoring neutral loss scan of 141 Da; and phosphatidylserines detected using neutral loss scan of 184 Da. Molecular ions [M-H]- were instead acquired in negative precursor ion scan of m/z 153 for the classes of phosphatidic acids and phosphatidylglycerols; and of m/z 241 for the phosphatidylinositols. For the identification of the single molecular species, product ion scan mass spectra of the [M + HCOO]- ions for phosphatidylcholines and [M + H]+ ions for the other phospholipids considered were determined for each class and compared with the fragmentation pattern of model phospholipid reference standard. By this approach, nearly 100 phospholipids and sphingomyelins were detected and identified. The optimized method was then used to characterize the phospholipid and sphingomyelin profiles in human plasma and urine samples and in two phospholipid-based pharmaceutical formulations, proving that it also allows to discriminate compounds of endogenous origin from those resulting from the intake of pharmaceutical products containing phospholipidic liposomes. Copyright © 2016 John Wiley & Sons, Ltd.

Rapid evaluation of 25 key sphingolipids and phosphosphingolipids in human plasma by LC-MS/MS.

We report on a new, sensitive, and fast LC-MS/MS method for the simultaneous determination of 25 key sphingolipid components in human plasma, including phosphorylated sphinganine and sphingosine, in a single 9-min run. This method enables an effective and high-throughput coverage of the metabolic changes involving the sphingolipidome during physiological or pathological states. The method is based on liquid-liquid extraction followed by reversed-phase LC-MS/MS. Exogenous odd-chain lipids are used as cost-effective but reliable internal standards. The method was fully validated in surrogate matrix and naive human plasma following FDA guidelines. Sample stability and dilution integrity were also tested and verified.

[Assessment of some biophysical parameters of human erythrocyte by FT-IR spectroscopy--preliminary study]. / Evaluarea unor parametri biofizici ai eritrocitului uman prin spectroscopie FT-IR--studiu preliminar.

UNLABELLED: Based on the biochemical composition of erythrocyte membrane and asymmetric distribution of phospholipids, proteins, and cholesterol, FT-IR spectroscopy can monitor the distribution and interaction pattern of membrane constituents. MATERIAL AND METHODS: The study series included 21 clinically healthy subjects aged between 20 and 60 years. Complete blood counts were performed and the serum biochemical compounds (cholesterol, triglycerides, total protein, glucose) were determined. RESULTS AND DISCUSSIONS: The parameters that can be assessed by erythrocyte FT-IR in relation with the biochemical factors that may influence membrane fluidity are: degree of fatty acids unsaturation, saturated fatty acids/unsaturated fatty acids ratio, cholesterol/phospholipids ratio, and phospholipids/protein ratio. Based on the obtained results, in the assessment of membrane status the following vibration modes were selected as spectral parameters: vibration associated valence bond (=CH), asymmetric valence CH2 groups, modes associated with P=O bond and amine bands I and II specific for proteins. Other parameters, such as v(C-O) specific to glucose, may provide additional information on glucose metabolic status. CONCLUSIONS: By correlating biochemical markers with these spectral parameters information on red cell membrane status, status that may reflect different pathological processes, can be obtained.

Antiobesity effects of Undaria lipid capsules prepared with scallop phospholipids.

Based on previous research findings, a capsule was developed containing n-3 polyunsaturated fatty acid rich scallop phospholipids (PLs) with an incorporation of brown seaweed (Undaria pinnatifida) lipids (ULs) containing fucoxanthin. The antiobesity effects of the capsules were evaluated with an animal model using 3-wk-old male KK-A(y) mice. Each group received different combinations of lipid (UL, PL, UL + PL, or UL + PL capsule) either incorporated into the diet or into drinking water. Animals were sacrificed after a 4-wk experimental feeding period, and adipose tissues and organs were dissected and weighed. Blood samples were obtained to determine plasma lipid profiles. Uncoupling protein 1 (UCP1) mRNA expression levels were determined by real-time polymerase chain reaction analysis, and UCP1 expression was determined by western blotting analysis. Treatment with either UL alone or UL + PL (capsule) through drinking water resulted in a significant reduction in body weight, compared to the control group. The total white adipose tissue weight of mice fed the UL + PL capsule in drinking water was significantly reduced. Both UCP1 and UCP1 mRNA expression in epididymal fat from mice fed the capsule were significantly higher than in the control group. These results suggest that incorporation of UL into scallop-derived PL by means of capsulation may lead to an additive increase in the antiobesity properties of these bioactive lipids.

[Assessment of malonyldialdehyde concentration as a product of lipid peroxidation and lipid metabolism in patients on chronic dialysis]. / Ocena stezenia malonylodialdehydu jako produktu peroksydacji lipidów a gospodarka lipidowa u chorych przewlekle dializowanych.

UNLABELLED: Chronic hemodialysis in patients with renal insufficiency is a factor significantly intensifying oxidative stress, resulting in increased lipid and lipoprotein peroxidation. It intensifies atherosclerotic activity. Malonyldialdehyde (MDA) concentration in serum, and isolated fraction of low density lipoprotein is indicators of lipid peroxidation intensification and therefore arteriosclerosis development. THE AIM OF THE STUDY: Assessment of MDA concentration as a product of lipid peroxidation and lipid metabolism in patients on chronic dialysis. MATERIALS AND METHODS: The study included 48 dialyzed patients, age 22-68 undergoing chronic dialysis for, on average, 56 months. On account of dialysis period the patients were included into 3 subgroups: group 1 (n = 17) dialysis period 2 years, group 2 (n = 13) dialysis period 2-5 years and group 3 (n = 18) dialysis period longer than 5 years. Control group consisted of 30 healthy subjects. We assessed: malonyldialdehyde in serum and isolated fraction of low density lipids (LDL) and high density lipid (HDL) and cholesterol (CH) and triglycerides (TG), phospholipids (PL) in serum and isolated lipoprotein fractions. RESULTS: Significantly decreased levels of HDL, LDL fractions and increased triglicerides and elevated levels of MDA in serum and isolated LDL fraction were found in patients on chronic dialysis in comparison to control group (p < 0.05). CONCLUSION: Our results indicate apparent normalization of lipid metabolism in patients on chronic dialysis and suggest that MDA assessment is better marker for arteriosclerosis risk estimation in long-term dialyzed patients.

Assessment of erythrocyte phospholipid fatty acid composition as a biomarker for dietary MUFA, PUFA or saturated fatty acid intake in a controlled cross-over intervention trial.

BACKGROUND: Dietary intervention trials rely on self-reported measures of intake for assessment of energy and macronutrient composition. Dietary fat intake is of particular interest due to strong associations with pathophysiology. In epidemiological trials phospholipid fatty acid composition may reflect composition of habitual diet, although strong correlations have been identified only for essential polyunsaturated fatty acids (PUFAs). Preliminary evidence shows that saturated fatty acids (SFA) C15:0 and C17:0 may be acceptable biomarkers. This study measured changes in erythrocyte membrane fatty acids during a period of strictly controlled fat feeding to investigate their use as a short-term marker of compliance, particularly for intake of SFAs. RESULTS: This was a randomised cross-over trial in which diet was provided and strictly controlled. 20 healthy, male subjects were given a 40 energy % (en%) fat diet, high in saturated (high-SFA, 20 en%) or unsaturated (high-USFA, 24 en%) fatty acids for 2 periods of 3 weeks. Subjects were residential during intervention with all food and beverages provided. Dietary composition was verified by direct chemical analysis. Blood samples were collected on days 1,7,14, 21 and analysed for red blood cell (RBC) membrane fatty acid composition. Pearson correlation showed RBC fatty acid composition to mimic dietary composition by 3 weeks, but the relationships were weak. Of the SFAs only RBC C16:0 decreased in response to decreased dietary content on high-USFA treatment (ANOVA, diet, P < 0.05). Of the USFAs, higher levels of C18:1 MUFA, C20:4 and C22:6 long chain PUFA on high-USFA diet lead to higher C18:1, C20:4 and C22:6 within RBCs (ANOVA, time*diet, P < 0.05). Pearson's correlation was significant between dietary and RBC fatty acids during the 21d dietary manipulation for C18:1, and C20:5, C22:6 only (P < 0.05). CONCLUSION: RBC membrane fatty acids cannot reliably be used as an independent measure of compliance for dietary SFA intake in short-term studies. The MUFA oleic acid and PUFAs EPA and DHA may be more useful as markers of compliance during short term intervention trials.

Dietary conjugated linoleic acid (CLA) intake assessment and possible biomarkers of CLA intake in young women.

OBJECTIVE: The habitual intake of the conjugated linoleic acid (CLA) isomer C18:2 c9t11 (rumenic acid, RA) was assessed and compared with plasma biomarkers. DESIGN: The newly developed food-frequency questionnaire (FFQ) comprised 46 food items and was validated by means of a 7-day estimated record (7-d ER). Additionally, the dietary intake results of the FFQ, 7-d ER, the last day (1-d ER) and the last two days (2-d ER) before blood sampling of the 7-d ER were compared to the content of C18:2 c9t11 in plasma phospholipids (PL) and triglycerides (TG) as possible biomarkers. SETTING: Metabolic unit of a university institute. SUBJECTS: Fifty-seven students completed both dietary instruments. From all participants fasting blood samples were taken. RESULTS: Mean daily intake of rumenic acid was 246 mg day(-1) and 323 mg day(-1) as measured by the FFQ and the 7-d-ER, respectively. The degree of correspondence between both assessment methods was acceptable; this is indicated by a total kappa value of kappa = 0.31 (P < 0.01) and a Pearson correlation coefficient of r = 0.46 (P < 0.01). Rumenic acid content in plasma triglycerides was twice as high as found in phospholipids. The correlation between the intake results gained with the 7-d ER and the plasma PL contents of C18:2 c9t11 was statistically significant; this was also true for the C18:2 c9tl 1 values in plasma TG compared with the intake results of one or two days before blood sampling. CONCLUSIONS: Regarding RA intake, the FFQ data revealed an acceptable degree of correspondence with the 7-d ER data but failed to show significant correlations to the potential biomarkers. However, with respect to the results of the 7-d ER, the RA content in plasma PL and TG are possible biomarkers of short-term and medium-term intake, respectively.

Essential fatty acid status in cell membranes and plasma of patients with primary Sjogren's syndrome. Correlations to clinical and immunologic variables using a new model for classification and assessment of disease manifestations.

In 41 primary Sjögren's syndrome patients we compared fatty acid levels within erythrocyte phospholipids, plasma phospholipids, plasma triglycerides and plasma cholesterol esters, with the immunopathological and clinical disease status. Docosahexaenoic acid was the essential fatty acid (EFA), the levels of which correlated (inversely) most closely with the clinical disease status (r=-0.33 to -0.50). Levels of dihomogammalinolenic acid and eicosapentaenoic acid correlated inversely to levels of IgM rheumatoid factors (r=-0.33) and anti-SSA/Ro antibodies (r=-0.40) respectively. Moreover, levels of anti-SSA/Ro antibodies (r=-0.34-0.40) correlated with levels of the proinflammatory arachidonic acid. Sigma n-3 EFA/sigma n-6 EFA ratios correlated significantly to the quantitative estimates of immunopathological and clinical disease status. Our data are in agreement with current understanding of pro- and anti-immunoinflammatory roles within EFA metabolism, and support the rationale for intervention studies.

Application of hepatic tolerance tests to the functional reserve assessment in rat models of fatty liver.

The present study was designed to define whether maximal removal rate of indocyanine green (ICG Rmax), plasma cyclic 3',5'-adenosine monophosphate (cAMP) response to exogenous glucagon (peak to basal ratio of cAMP level: P/B cAMP) and plasma half-life of galactose (t1/2 galactose) can measure the hepatic functional reserve of fatty liver prepared in rats fed choline-deficient (9 weeks), 2% cholesterol (2 weeks) or 0.25% DL-ethionine (2 weeks) diet. Although changes in cholesterol and phospholipid values in serum during feeding periods differed among the models, histopathologic examinations in the liver of almost all animals revealed intermediate to severe fatty liver with or without fibrosis at each termination. ICG Rmax and P/B cAMP were significantly decreased in rats fed choline-deficient or DL-ethionine diet, implying reductions in hepatic functional mass and disturbances in hepatic cAMP production. Meanwhile, t1/2 galactose showed no change in any of the models, suggesting that glucose metabolisms in the models used may be preserved. These findings demonstrate that ICG Rmax and P/B cAMP can apply to measurement of hepatic surviving reserve of fatty liver with fibrosis.

Biochemical assessment of the nutritional status of cystic fibrosis patients treated with pancreatic enzyme extracts.

We examined the protein and fat nutritional status of 65 cystic fibrosis patients aged 4-26 y (x +/- SD: 11.2 +/- 5.6 y). Patients were treated with pancreatic enzyme extracts to improve nutrient absorption; in addition, most patients were supplemented with vitamins A and E. Results were compared with those in a control group of 39 subjects aged 5-29 y (x: 14.3 +/- 5.6 y) with no digestive diseases or nutritional deficiencies. Protein determination showed low albumin concentrations in 42% of the cystic fibrosis patients and decreased blood concentrations of retinol binding protein in 12% of the patients. Lipoprotein components were characterized by decreased cholesterol concentrations in 25% of the cystic fibrosis group. Also, mean concentrations of apolipoprotein A-I were significantly lower in the cystic fibrosis group than in control subjects. The results of fatty acid status, expressed in relative (%) and absolute (mg/L) values, showed concentrations of essential fatty acids, represented by linoleic and arachidonic acids, to be significantly decreased in cystic fibrosis patients; this decrease was markedly significant for fatty acid status expressed in absolute values, especially in the cholesteryl ester subfraction. Serum retinol and alpha-tocopherol concentrations were lowered by 8% and 46% in cystic fibrosis patients and control subjects, respectively: retinol, 1.80 +/- 0.50 and 2.37 +/- 0.60 micromol/L, P < 0.001, and alpha-tocopherol, 18.1 +/- 8.7 and 25.7 +/- 5.0 micromol/L, P < 0.001. In conclusion, despite regular treatment with pancreatic enzyme replacements, neither protein nor fat malnutrition in cystic fibrosis patients was completely corrected.

Assessment of the efficacious dose of arachidonic and docosahexaenoic acids in preterm infant formulas: fatty acid composition of erythrocyte membrane lipids.

The nutritional requirements of preterm infants for the long chain polyunsaturated essential fatty acids, arachidonic acid (AA) and docosahexaenoic acid (DHA), have not been clearly defined. The present study evaluated preterm infants of less than 2.3 kg birth weight fed a commercial formula (Preemie SMA) devoid of AA and DHA and compared this control group with similar infant groups fed one of three formulas containing a range of 0.32 to 1.1% AA and 0.24 to 0.76% DHA. An analogous group of infants fed their mothers' breast milk and a breast milk fortifier (when indicated) was also studied. Erythrocyte membrane phospholipids were isolated from blood samples collected at 12 d of age and after a further 4 wk of feeding. Infants fed the formula without AA and DHA showed a reduction in AA level in erythrocyte phosphatidylcholine, and a reduced level of DHA in phosphatidylethanolamine in comparison with infants fed breast milk or infant formula containing AA and DHA. Supplementing infant formula with increasing levels of AA and DHA produced a clear dose response in the levels of AA and DHA found in erythrocyte membrane phospholipids. From comparison of membrane phospholipid fatty acid composition it appears that a formula level of 0.32-1.1% AA and 0.24-0.76% DHA provides sufficient levels of these fatty acids to achieve a similar fatty acid composition to that of infants fed human milk for most of the lipid fractions examined.

An assessment of docosahexaenoic acid (DHA) intake with special reference to lipid metabolism in rats.

In order to determine the appropriate intake of docosahexaenoic acid (22:6n-3, DHA), the potential changes in lipid peroxidation and antioxidant defense in serum and tissue as well as the changes in serum lipid levels were examined in rats by giving them diets containing graded levels of purified DHA (0, 1.0, 3.4 and 8.7 energy % in the diets) for 2 weeks. Serum alpha-tocopherol concentration decreased slightly but significantly even at the 1.0 energy %. Liver lipid peroxide levels as assessed by the thiobarbituric acid (TBA) value and chemiluminescence intensity augmented at the 3.4 energy % and more, and the alpha-tocopherol content significantly decreased in response to the increase in lipid peroxide levels. In the kidney, a slight but significant increase in TBA value was observed even at 1.0 energy % and higher. All the serum lipid levels as analyzed by total cholesterol, HDL-cholesterol, triacylglycerol (TG) and phospholipids (PLs) decreased as the dietary DHA level increased. These experimental results suggest that the dietary intake of DHA should be less than 1 energy % to avoid promoting deleterious influences such as serum and tissue lipid peroxidation and to ameliorate serum lipid levels.

Once-a-day administration of amikacin in neonates: assessment of nephrotoxicity and ototoxicity.

Neonates, especially preterms, are known to have low glomerular filtration rates (GFR). This may result in elevated trough concentrations during multiple administration of aminoglycosides (AGs), potentially leading to nephro- and ototoxic reactions. The once-daily administration (q.d.) of AGs has been shown to be equally or better tolerated in adults and children than the conventional schedules (twice daily, b.i.d.; thrice daily, t.i.d.), while offering potential pharmacodynamic and nursing advantages. No data, however, are available for neonates. As a consequence, this pilot study was conducted in order to assess the tolerance of the once-a-day administration of amikacin in comparison with the twice daily dose regimen, in relation to the pharmacokinetics of the drug under these two schedules. 22 Male neonates (gestational age > or = 34 weeks; postnatal age < or = 2 days) were randomized to receive amikacin (AK) (15 mg/kg/day) q.d. (n = 10) or b.i.d. (n = 12) together with ampicillin (50 mg/kg/12 h). AK plasma levels were measured at days 1, 3, 5 and 7 of treatment just before the next dose (trough level) and 1 h after completion of infusion (peak level) and after 3 and 6 h only at day 1. Due to the small size of the samples, no difference in efficacy could be assessed and was not the aim per se. Glomerular dysfunction was assessed by creatinine clearance, and tubular injuries by the urinary excretion of proteins (retinol binding protein, beta 2-microglobulin, clara cell protein (P1) and microalbumin), enzymes (N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, alanine aminopeptidase, and gamma-glutamyltransferase), and total phospholipids (TPL) in urine. Ototoxicity was assessed by brainstem auditory evoked potentials (BAEPs) at days 0, 3 and 9 of therapy. Eight healthy neonates served as controls. All patients showed a normal and similar increase of GFR during the first postnatal days. Proteinuria did not increase, but enzymuria and TPL increased significantly during the treatment in both AK groups without significant difference between groups. BAEPs at day 9 were not significantly different between treated and untreated patients. We conclude from this pilot study that, in the absence of more toxicity, the q.d. administration of AK in neonates of > or = 34 weeks of gestational age may be recommended over its bid schedule in view of its potential advantages.

Biochemical assessment of cholelithiasis.

Bile and serum were analysed in 45 cases of cholelithiasis and 25 control subjects for cholesterol, phospholipids, bilirubin, alkaline phosphatase and LCAT activity. Serum phospholipids were found to be elevated in sixty percent of cases, whereas phospholipids in bile were found to be decreased. Serum alkaline phosphatase and alanine aminotransferase were normal. Serum and bile LCAT activity was found to be significantly depressed.

Changes in rat plasma apolipoproteins and lipoproteins during moderate protein deficiency: potential use in the assessment of nutritional status.

To test apolipoprotein sensitivity as protein deficiency markers, concomitant evolution of plasma apolipoproteins (apo) and usual nutritional markers (transthyretin, albumin, transferrin) were followed during a 28-d protein restriction in young male Wistar rats. In addition, plasma lipids and chemical composition of lipoproteins were assayed by d 28. The control and the deficient groups were fed 18% and 6% casein diets, respectively. By d 28 the protein-deficient group exhibited hypotriglyceridemia resulting from the decrease in VLDL triacylglycerols; free cholesterol and phospholipids were increased, reflecting the increment in LDL-HLDL1. In plasma total lipoproteins, apo BH, AI and E were not different than controls in the deficient group. Apolipoprotein AIV decreased after d 14 and was significantly less than in controls at d 28. Apolipoprotein BI was considerably reduced by d 14 (43% less) and d 28 (52% less) compared with the control group. Apolipoproteins C + AII were significantly lower in the protein-deficient group by d 14 (43%). By d 28, VLDL apo C were decreased 60% by protein restriction. Transthyretin level was 20% lower in the protein-deficient group by d 7 but returned to control values by d 14. A moderately lower value was observed for albumin by d 7 and d 14 and for transferrin by d 28. These results indicate that, in this model, apo BI and C are more sensitive to protein depletion than usual nutritional markers.

[A clinico-pathogenetic assessment of the membrane structure and functions of the peripheral blood lymphocytes in insulin-dependent diabetes mellitus]. / Kliniko-patogeneticheskaia otsenka struktury i funktsii membran limfotsitov perifericheskoi krovi pri insulinzavisimom sakharnom diabete.

The structure and functions of lymphocyte membranes with characterization of their phospholipid composition, lipid peroxidation intensity (LP), activity of membranous ATPases and a type of the immune status were investigated in patients with insulin dependent diabetes mellitus. The results obtained were indicative of considerable differences (LP) in the lymphocytes of these patients as compared to those of healthy controls. LP intensity showed correlation with change in the ratio of phospholipid fractions and change in ATPase activity. In complicated insulin dependent diabetes mellitus destabilization of lymphocyte cell membranes and disturbance of transmembranous transport were more marked than in uncomplicated disease. The structure and functions of the membranes of immunocompetent cells, a degree of carbohydrate metabolic decompensation and the presence of complications determined an immune response type.