Regulación por micro RNA de la respuesta angiogénica en la retina diabética / Micro-RNA regulation of the angiogenic response in the diabetic retina

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Beneficial contribution of a safflower (Carthamus tinctorius L.) polysaccharide on steroid-induced avascular necrosis of the femoral head in rats.

A water-soluble polysaccharide (SPS) was purified from dried safflower (Carthamus tinctorius L.) and its structure was identified using a combination of chemical and instrumental analysis. SPS has a repeating backbone of 1,4,6-ß-Glcp, which was attached with T-ß-Glcp at its C6 position along the main chain in the molar ratio of 1:1. A steroid-induced avascular necrosis of the femoral head (SANFH) model was established in mice injected with dexamethasone (50 mg/kg) twice per week for 6 weeks. Following SPS treatment at 25 and 100 mg/kg for 60 days, the decreased bone mineral density, abnormal histopathological changes, the increased rate of empty lacunae and apoptosis rate of osteocytes of femoral head in mice induced by dexamethasone was significantly reversed. Meanwhile, increased serum hydroxyproline (HOP) and decreased serum hexosamine (HOM) concentration in mice were turned to the opposite trend with increasing dosage of SPS, thus leading to a high rate of HOM/HOP. In conclusion, SPS may serve as a potential agent for the treatment of SANFH.

Quantitative hydrophilic interaction chromatography-mass spectrometry analysis of N-acetylneuraminic acid and N-acetylmannosamine in human plasma.

N-acetylneuraminic acid (Neu5Ac or NANA) is the most predominant sialic acid in mammals. As a terminal component in many glycoproteins and glycolipids, sialic acid is believed to be an important biomarker related to various diseases. Its precursor, N-acetylmannosamine (ManNAc), is being investigated as a potential treatment for GNE myopathy. In this work, we developed two highly sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for the quantitation of ManNAc and free Neu5Ac in human plasma. A fit-for-purpose approach was adopted during method validation and sample analysis. To measure the endogenous compounds and overcome the interference from plasma samples, a surrogate matrix that contained 5% bovine serum albumin (BSA) was used for the preparation of calibration standards and certain levels of quality control (QC) samples. QC samples at higher concentrations were prepared in the authentic matrix (human plasma) to best mimic incurred samples. For both methods, an Ostro 96-well phospholipid removal plate was used for sample extraction, which efficiently removed the phospholipids from the plasma samples prior to LC injection, eliminated matrix effect, and improved sensitivity. Chromatographic separation was achieved using hydrophilic interaction chromatography (HILIC) and gradient elution in order to retain the two polar compounds. The lower limit of quantitation (LLOQ) for ManNAc and Neu5Ac was 10.0 and 25.0ng/mL, respectively. The overall accuracy of the two assays was within 100%±8.3% based on three levels of QC samples. Inter- and intra-run precision (coefficient of variation (%CV)) across three analytical runs was less than 6.7% for ManNAc and less than 10.8% for Neu5Ac. These methods have been validated to support clinical studies.

Non-specific accumulation of glycosphingolipids in GNE myopathy.

BACKGROUND: UDP-GlcNAc 2-epimerase/ManNAc 6-kinase (GNE) is a bifunctional enzyme responsible for the first committed steps in the synthesis of sialic acid, a common terminal monosaccharide in both protein and lipid glycosylation. GNE mutations are responsible for a rare autosomal recessive neuromuscular disorder, GNE myopathy (also called hereditary inclusion body myopathy). The connection between the impairment of sialic acid synthesis and muscle pathology in GNE myopathy remains poorly understood. METHODS: Glycosphingolipid (GSL) analysis was performed by HPLC in multiple models of GNE myopathy, including patients' fibroblasts and plasma, control fibroblasts with inhibited GNE epimerase activity through a novel imino sugar, and tissues of Gne(M712T/M712T) knock-in mice. RESULTS: Not only neutral GSLs, but also sialylated GSLs, were significantly increased compared to controls in all tested models of GNE myopathy. Treatment of GNE myopathy fibroblasts with N-acetylmannosamine (ManNAc), a sialic acid precursor downstream of GNE epimerase activity, ameliorated the increased total GSL concentrations. CONCLUSION: GNE myopathy models have increased total GSL concentrations. ManNAc supplementation results in decrease of GSL levels, linking abnormal increase of total GSLs in GNE myopathy to defects in the sialic acid biosynthetic pathway. These data advocate for further exploring GSL concentrations as an informative biomarker, not only for GNE myopathy, but also for other disorders of sialic acid metabolism.

Protective effect of Cardiospermum halicacabum leaf extract on glycoprotein components on STZ-induced hyperglycemic rats.

OBJECTIVE: To investigate the protective role of Cardiospermum halicacabum (C. halicacabum) leaf extract on glycoprotein metabolism in streptozotocin (STZ)-induced diabetic rats. METHODS: Diabetes was induced in male albino Wistar rats by intraperitonial administration of STZ. The C. halicacabum leaf extract (CHE) was administered orally to normal and STZ-diabetic rats for 45 days. The effects of C. halicacabum leaf extract (CHE) on plasma and tissue glycoproteins (hexose, hexosamine, fucose and sialic acid) were determined. RESULTS: The levels of plasma and tissues glycoproteins containing hexose, hexosamine and fucose were significantly increased in STZ-induced diabetic rats. In addition, the level of sialic acid significantly increased in plasma and liver while decreased in kidney of STZ-induced diabetic rats. After administration of CHE to diabetic rats, the metabolic alteration of glycoprotein reverted towards normal levels. CONCLUSIONS: The present study indicates that the CHE possesses a protective effect on abnormal glycoprotein metabolism in addition to its antihyperglycemic activity.

Changes in plasma and IgG N-glycome during childhood and adolescence.

Despite the importance of protein glycosylation in all physiological and pathological processes and their potential as diagnostic markers and drug targets, the glycome of children is still unexplored. We analyzed N-linked plasma and IgG glycomes in 170 children and adolescents between 6 and 18 years of age. The results showed large biological variability at the population level as well as a large number of associations between different glycans and age. The plasma N-glycome of younger children was found to contain a larger proportion of large complex glycan structures (r = -0.71 for tetrasialylated glycans; r = -0.41 for trisialylated glycans) as well as an increase in disialylated biantennary structures (r = 0.55) with age. Core fucosylation and the level of agalactosylated plasma and IgG glycans decreased while digalactosylated glycans increased with age. This pattern of age-dependent changes in children differs from changes reported in adult population in both, direction and the intensity of changes. Also, sex differences are much smaller in children than in adults and are present mainly during puberty. These important observations should be accounted for when glycan-based diagnostic tests or therapeutics are being developed or evaluated.

Effect of antler extract on corticosteroid-induced avascular necrosis of the femoral head in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Deer antler, traditionally used as a tonic and valuable drug in oriental medicine, has been considered to possess bone-strengthening activity and effectively used in bone diseases therapy. AIM OF THE STUDY: The present study was designed to investigate therapeutic effect of antler extract on avascular necrosis of the femoral head (ANFH) induced by corticosteroids in rats. MATERIALS AND METHODS: Rats were intragluteally injected with dexamethasone at 50mg/kg twice per week for 6 weeks to induce ANFH. Then the rats were treated with antler extract by oral gavage at 200mg/kg, 400mg/kg and 800 mg/kg once per day for 60 days. The concentration of hydroxyproline and hexosamine in serum was measured and the ultrastructure of femoral head was examined. In vitro, effect of the drug-containing serum of antler extract on proliferation and differentiation of primary osteoblasts were investigated by MIT assay, ALP activity assay and cell cycle analysis. RESULTS: After treatment with antler extract, the degree of necrosis induced by dexamethasone was significantly reduced, hydroxyproline was significantly decreased, and hexosamine and the ratio of hexosamine/hydroxyproline were significantly increased. The drug-containing serum of antler extract promotes osteoblastic proliferation through regulation of cell cycle progression. CONCLUSIONS: The results suggest that antler extract has a positive curative effect on ANFH by promoting osteoblastic proliferation.

A direct HPLC method to estimate streptomycin and its putative ototoxic derivative, streptidine, in blood serum: application to streptomycin-treated humans.

Streptomycin is an aminoglycoside antibiotic with a well-known antituberculosis activity; it is commonly used in clinical practice because it is effective and cheap. However, streptomycin has severe ototoxic effects. The delayed and gradual onset may suggest that a metabolic derivative of the antibiotic could be a potential contributor to ototoxicity. As in a rat experimental model this compound was found to be streptidine, we investigated whether this ototoxic metabolite was also present in the blood of streptomycin-treated patients. To this end, we implemented and optimized a direct reverse-phase HPLC technique to identify and estimate streptomycin and streptidine in serum of streptomycin-treated patients. All criteria for validation of the method were implemented in standard curves in serum of healthy non-treated volunteers by addition of increasing concentration of both compounds and their determination in a trichloroacetic acid deproteinized extract. We found that recovery of streptomycin or streptidine was > or =91.5%. Linearity was r(2)> or =0.99. The intraday and interday precisions were < or =9.7 and < or =10.6%, respectively. The relative intraday and interday error ranged from -9.0 to 8.3% for both compounds in human serum. Studies in patients included five male individuals treated from 35 to 90 days with 1g/day of streptomycin, presenting inner ear malfunction from mild to severe, in whose serum streptidine was always present, and could be successfully separated from streptomycin. Therefore, the validated method used can be a valuable tool to measure and follow these compounds in serum of streptomycin-treated patients.

Comparison of blood protein levels between diabetic and non-diabetic patients with retinopathy.

OBJECTIVE: To compare serum protein levels between diabetic and non-diabetic patients with retinopathy. STUDY DESIGN: Comparative study. PLACE AND DURATION: Ziauddin Medical University and Jinnah Postgraduate Medical Centre, Karachi, Pakistan, from 2000 to 2002. PATIENTS AND METHODS: Sixty patients were selected. Among them, 21 were diabetic patients without any clinical evidence of chronic diabetic complications; 20 were diabetic patients with retinopathy and 19 were non-diabetic patients with retinopathy. Twenty-one apparently normal, age, gender and weight-matched control subjects were also inducted. All these patients were selected on clinical grounds. Blood values, fasting plasma glucose, glycosylated hemoglobin, serum fructosamine, glycosylated plasma protein, hexosamine, sialic acid and total serum proteins were determined and compared. RESULTS: Fasting plasma glucose was high in all diabetic patients and correlated significantly with glycosylated hemoglobin, glycosylated plasma proteins and serum fructosamine concentrations. Fasting plasma glucose, glycosylated hemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum protein were increased in diabetic patients with retinopathy and diabetic patients without any complications. These values were not different in diabetic patients with retinopathy and diabetic patients without chronic complications as compared with control subjects. Alpha-1 and alpha-2 globulins were significantly increased in diabetic patients with retinopathy, diabetic patients without complications and non-diabetic patients with retinopathy as compared with control subjects. Beta globulin was significantly increased in diabetic patients with retinopathy as compared with non-diabetic patients with retinopathy, diabetic patients without complication and control subjects. Gamma globulin was significantly decreased in diabetic and non-diabetic patients with retinopathy. CONCLUSION: Fasting plasma glucose, glycosylated hemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum protein were increased in diabetic patients with and without complications but these parameters remained within normal limits in non-diabetic patients with retinopathy. The decrease in gamma globulins may be associated with a retinopathy.

A case control study of glycoprotein status in ovarian carcinoma.

OBJECTIVES: Ovarian cancer is the leading cause of death due to gynecological malignancies. The aim of our study was to investigate the status of circulating glycoprotein levels in ovarian cancer patients. DESIGN AND METHODS: Thirty ovarian cancer patients and an equal number of age-matched, apparently healthy subjects as controls were involved in the study. Glycoprotein levels, as indicated by the concentration of plasma total sialic acid, protein-bound hexoses, hexosamine and fucose were estimated in circulation of both the ovarian cancer patients and controls. RESULTS: Significantly elevated levels of plasma total sialic acid, protein-bound hexoses, hexosamine and fucose were observed in ovarian cancer patients as compared to the apparently healthy controls. CONCLUSION: Plasma total sialic acid, protein-bound hexoses, hexosamine and fucose in the circulation of ovarian cancer patients are markedly elevated and the increase in these carbohydrate moieties of glycoproteins reflect the stage of cancer and may be an additional tool in the diagnosis and prognosis of ovarian carcinoma.

Streptidine, a metabolic derivative produced after administration of streptomycin in vivo, is vestibulotoxic in rats.

Streptomycin is the treatment of choice in developing countries for patients suffering from tuberculosis or other infectious diseases. However, it produces incapacitating vestibular symptoms whose onset is delayed and gradual. This observation led to the notion that a streptomycin metabolic derivative and not the antibiotic itself is the damaging agent for the inner ear. To study further the existence of this ototoxic metabolite, chronic treatment with streptomycin or its putative derivative streptidine was carried out in young male Long Evans rats. The presence of streptomycin or streptidine in the blood of animals of either experimental group was assessed by high performance liquid chromatography and analysis of swimming behavior was used to evaluate vestibular damage. Features of the sensory epithelium and quantification of hair cells were attained in sections of the utricular organ of all groups by light microscopy. After 25, 35 and 45 days of treatment with streptomycin, a metabolite with the same chromatographic properties as the streptidine standard run in parallel was identified in the blood of rats. Concentrations of the metabolite were 2.26 microg/ml on the 25th day and around 8.0 microg/ml in both the 35th and the 45th day of treatment, while streptomycin was below its detection level at either period. In streptidine-treated rats, the concentration of this compound was 1.0, 1.84 and 4.94 microg/ml on the 25th, 35th and 45th treatment days, respectively. Treatment with either streptomycin or streptidine resulted in similar abnormal swimming patterns and histological alterations of the utricular epithelium. Loss of hair cells was roughly equivalent even though streptidine was administered in a dose 90% lower than streptomycin. The gradual appearance of streptidine as a metabolic derivative of the antibiotic in the blood of rats or the administration of this compound alone, causing similar functional and structural vestibular deterioration seen in streptomycin-treated animals, supports the notion that streptidine is a potential contributor to ototoxicity after prolonged antibiotic administration.

Membrane lipids and protein-bound carbohydrates status during the maturation of reticulocytes to erythrocytes in type 2 diabetics.

BACKGROUND: The reticulocyte maturation process is an ideal model for the study of biochemical alterations seen during final stage of erythropoiesis under disease conditions. In this study, determined whether type 2 diabetes has any effect on membrane lipids and protein-bound carbohydrates during the maturation of reticulocytes to erythrocytes. SUBJECTS AND METHODS: Lipids (cholesterol and phospholipids) and protein-bound carbohydrates (hexose, hexosamine and sialic acid) were extracted and estimated in plasma, membrane of reticulocytes and erythrocytes from 20 treated but uncontrolled type 2 diabetic volunteers and age matched controls. RESULTS: Plasma, membranes of reticulocytes and erythrocytes of diabetics showed increase in cholesterol (35.7%, 8.7% and 16.4%); phospholipids (43.4%, 18.8% and 8.2%); hexose (34.1%, 19.3% and 8.2%) and decrease in hexosamine (11.9%, 7.3% and 14.7%); and sialic acid (34.1%, 19.3% and 32.0%) compared to controls. As reticulocytes matured to erythrocytes, cholesterol, phospholipids, hexosamine and sialic acid levels were decreased; C/P ratio and hexose levels were increased in both controls and diabetics. However, these alterations were more intensified in diabetics. CONCLUSION: These alterations in diabetic patients may indicate the existence of one or both of the following conditions: acceleration of maturation processes and/or decreased red blood cell life span.

Analysis of glycoconjugates in patients with oral squamous cell carcinoma.

BACKGROUND: Our aim was to examine the levels of glycoconjugates in plasma, erythrocyte membranes and buccal mucosa of healthy subjects and oral cancer patients. SUBJECTS AND METHODS: This study was conducted on 48 adult male oral cancer patients with various clinical stages (stage II to stage IV; 16 of each) and 16 disease-free healthy subjects who underwent surgical removal of impacted teeth or vestibuloplasty without inflammation. RESULTS: The plasma and tumor tissues glycoconjugates levels were significantly increased, whereas the erythrocyte membranes glycoconjugates were significantly decreased in oral cancer patients as compared to healthy subjects. The levels of glycoconjugates were gradually increased from stage II to stage IV in plasma and tumor tissues and decreased in erythrocyte membranes from stage II to stage IV of oral cancer patients. CONCLUSION: The increased plasma glycoconjugates can be due to the expense of erythrocyte membrane glycoconjugates or tumor tissue itself.

Influence of sodium selenite on glycoprotein contents in normal and N-nitrosodiethylamine initiated and phenobarbital promoted rat liver tumors.

Selenium in the form of sodium selenite is an essential micronutrient, that acts as an antioxidant/anticancer agent by its numerous macromolecules associated with them. This study emphasizes further evidence on its role as anticancer agent in experimental rats with N-nitrosodiethylamine (DEN) initiated (200 mg kg(-1) body weight) and phenobarbital (PB) promoted hepatoma. Serum, whole liver tissue (control animals, n=6), hepatoma and surrounding liver tissue samples from DEN-treated rats and rats supplemented with selenite (n=6) were collected. Total protein, albumin, globulin and albumin/globulin ratio were investigated. Hexose, hexosamine and sialic acid were also quantified. Animals treated with DEN resulted in significantly decreased levels of total protein, albumin and albumin/globulin ratio; on the other hand, globulin content was increased significantly when compared to control rats. We have also observed significant increased levels of hexose, hexosamine and sialic acid in serum, whole liver tissue (control), hepatoma and surrounding liver tissue of control and experimental animals. Supplementation of selenite (4 ppm) either before initiation, during initiation and/or during promotion stages alters the above biochemical changes significantly. Thus, supplementations of selenite in cancer bearing animals reduce the adverse changes that occur during cancer condition. However, the chemopreventive/chemotherapeutic effect of selenite is more pronounced when it was supplemented before and/or during initiation of cancer when compared to promotion stage. Our results emphasize the role of sodium selenite in cancer and strongly indicate its role as an essential micronutrient in cancer chemoprevention and therapy.

Dietary lipids modulate bone prostaglandin E2 production, insulin-like growth factor-I concentration and formation rate in chicks.

This study examined the effects of dietary fat on the fatty acid composition of liver and bone, and on the concentration of insulin-like growth factor-I (IGF-I) in liver and bone, as well as the relationship of these factors to bone metabolism. Day-old male broiler chicks were given a semipurified diet containing one of four lipid sources: soybean oil (SBO), butter+corn oil (BC), margarine+corn oil (MAC), or menhaden oil+corn oil (MEC) at 70 g/kg of the diet. At 21 and 42 d of age, chicks fed MEC had the highest concentration of (n-3) fatty acids [20:5(n-3), 22:5(n-3) and 22:6(n-3)] in polar and neutral lipids of cortical bone but the lowest amount of 20:4(n-6) in polar lipids. Diets containing t-18:1 fatty acids (MAC and BC) resulted in t18:1 accumulation in bone and liver. Bone IGF-I concentration increased from 21 to 42 d in chicks given the SBO and BC diets. Tibial periosteal bone formation rate (BFR) was higher in chicks given BC compared with those consuming SBO and MEC at 21 d. The higher BFR and concentrations of hexosamine in serum and IGF-I in cartilage, but lower 20:4(n-6) content in bone polar lipids in chicks given BC compared with those given SBO suggest that BC optimized bone formation by altering the production of bone growth factors. A second study confirmed that dietary butter fat lowered ex vivo prostaglandin E2 production and increased trabecular BFR in chick tibia. These studies showed that dietary fat altered BFR perhaps by controlling the production of local regulatory factors in bone.

Microalbuminuria in obese patients with or without hypertension.

OBJECTIVE: To evaluate the prevalence in obese patients of an increased urinary albumin excretion rate (UAER) and the factors involved in this parameter. SUBJECTS: Two hundred and seven nondiabetic obese patients with BMI = 34.7 +/- 5.7 (SD) kg/m2. None had proteinuria or a history of nephropathy or uropathy. Fifty-two had moderate hypertension. A control group of 22 lean healthy subjects was also studied. MEASUREMENTS: The UAER was determined from 24-h urine samples by means of immunonephelemetry laser method. Creatinine clearance was calculated. Glycemia and plasma C peptide at fasting and 120 mine after glucose oral administration, HbA1c, serum fructosamine, plasma total cholesterol and triglycerides, HDL and LDL cholesterol were measured. Food intakes were determined by dietary history. RESULTS: Compared with the control group, the UAER was significantly higher in the obese patients (18.0 +/- 20.1 mg/24 h vs 3.2 +/- 2.8 mg/24 h, P < 0.0001). It was elevated (> 30 mg/24 h) in 25 obese patients (12.1%) and in particular, in 19.2% of the obese patients with hypertension. It was significantly higher in the patients with android or mixed (both android and gynoid) obesity than in those with gynoid obesity (p = 0.050). Log UAER correlated negatively with the duration of hypertension (p = 0.038) and was higher in the patients with familial hypertension than in those without (p = 0.002). Log UAER correlated strongly with log creatinine clearance (p < 0.0001) and fractional albumin clearance (p < 0.0001). It correlated significantly with fasting and 120 min after glucose plasma C peptide concentrations (p = 0.018 and p = 0.046, respectively). Creatinine clearance was significantly higher in the patients with android or mixed obesity than in those with gynoid obesity (p = 0.001). Log creatinine clearance correlated negatively with age (p = 0.046), and log LDL cholesterol (p = 0.025) and positively with log lipid caloric intake (p = 0.014). CONCLUSION: These results show the high prevalence of microalbuminuria in nondiabetic obese patients and suggest the involvement of renal hyperfiltration. Microalbuminuria may be an indicator of familial hypertension in obese subjects. Insulin resistance may be involved in the increase in the UAER. Nutritional factors, particularly lipid intake, may contribute to this increase in the UAER via an increase in glomerular hyperfiltration.

[The effect of fish oil on metabolic parameters in patients with type 2 diabetes mellitus associated with dyslipidemia]. / Ucinky rybích oleju na nekteré metabolické parametry nemocných s diabetes mellitus 2. typu a pruvodnou dyslipidémií.

BACKGROUND: The authors discuss the effect of administration of fish oils rich in n-3 fatty acids in diabetic patients type 2 and draw attention to the possible deterioration of glucose homeostasis. The objective of the investigation was to assess changes of the lipid and carbohydrate metabolism in type 2 diabetics with associated dyslipidaemia after enrichment of the diet with n-3 fatty acids. METHODS AND RESULTS: To 17 patients with type 2 diabetes and dyslipidaemia fish oil containing 5.5 g n-3 fatty acids per day was administered. After six weeks a decline of triglycerides was recorded (-47%, P < 0.01), free fatty acids (-27%, P < 0.01) and a rise of HDL2-cholesterol (25%, P < 0.05). The concentration of apo B, apo A-1, LDL- and HDL cholesterol did not change significantly. There were no significant changes of the blood sugar level, glycosylated haemoglobin and fructosamine. The insulin and C-peptide concentration on fasting (and after glucagon stimulation) did not change significantly. With regard to the HDL2-cholesterol and 18:0 fatty acid concentration in serum the group can be divided into responders (with a decline of glycosylated haemoglobin) and non-responders. The two groups have a reverse trend of blood sugar levels and insulinaemia and differ as to the metabolism of 18:1 n-7 acid. CONCLUSIONS: Enrichment of the diet with n-3 fatty acids in diabetics with dyslipidaemia has a favourable effect on the plasma lipid spectrum without causing deterioration of parameters of diabetes compensation. Among the group of patients some can be found where fish oil administration improves also glucose homeostasis.

Marine lipids normalize cholesteryl ester transfer in IDDM.

Patients with insulin-dependent diabetes mellitus (IDDM) have a pathological increase in cholesteryl ester transfer (CET) that enriches the apolipoprotein B-containing lipoproteins with cholesteryl ester and increases their atherogenicity. Since we have shown earlier that omega-3 (n-3) fatty acids present in marine lipids normalize both CET and lipoprotein composition in non-diabetic patients with hypercholesterolaemia, we sought to determine whether the same beneficial effects could be achieved in nine normolipidaemic (triglycerides 1.10; cholesterol 4.94, high density lipoprotein 1.10 mmol/l) IDDM patients (fructosamine 424 +/- 156; normal 174-286 mumol/l) treated for 2 months with n-3 fatty acids (4.6 g/day). Before treatment, CET measured by both mass and isotopic assays was abnormally accelerated (p < 0.001). While marine lipids modestly decreased triglyceride levels (-14%; p < 0.05 ), CET fell dramatically in all subjects (mass assay: -97% at 1 h; isotopic assay: -58%; p < 0.001) to below control levels with no change in glycaemic control (fructosamine 408 +/- 103 mumol/l). The mass of cholesteryl ester transfer protein paradoxically increased significantly (pre-treatment: 2.04 +/- 0.86 vs post-treatment 2.48 +/- 0.97 micrograms/ml; p < 0.05). Since it is believed that accelerated CET promotes the formation of atherogenic cholesteryl ester-enriched apo B-containing lipoproteins, the capacity of marine lipids to reverse this functional abnormality without altering glycaemic control suggests that these agents may have an adjunctive role to play in the nutritional therapy of IDDM.