Effect of Arthrospira powders from different producers on the formation of endothelial cell monolayers.

Arthrospira platensis (AP) and some of its derived products have well-established biological activities as antioxidants or as agents to reduce cardiovascular disease risk factors. Furthermore, AP products have gained increasing importance as potential anti-cancer agents. However, the ingredients of the available products vary greatly with the origin, the type of production and processing, which could have significant consequences for their biological effects. Therefore, the composition and biological influence of five distinct AP powders, which were acquired commercially or produced at a public biotechnology institute, were investigated in regard to their endothelialization capacity using a cell impedance- (CI) based measurement method. The study revealed that the AP composition and especially the influence on HUVEC proliferation differed significantly between the five AP powders up to 109%.Thus, it could be shown that the method used allows the reliable detection of quantitative differences in biological effects of different AP preparations.

[Preoperative iron deficiency with/without anemia-an underestimated risk factor?] / Präoperativer Eisenmangel mit/ohne Anämie ­ ein unterschätzter Risikofaktor?

BACKGROUND: Every third surgical patient already suffers from anemia before surgery. The main cause is iron deficiency. OBJECTIVE: This article describes the perioperative risk of iron deficiency with/without anemia and summarizes potential preventive measures. MATERIAL AND METHODS: Presentation of various current original papers, guidelines and own experiences from the German patient blood management network. RESULTS AND CONCLUSION: Preoperative iron deficiency with/without anemia is an underestimated risk factor for perioperative complications. The implementation of preoperative diagnostics and treatment as part of a comprehensive patient blood management reduces complications and increases patient safety.

Successful treatment of severe ABO antibody-mediated rejection using bortezomib: a case report.

BACKGROUND: Our program for ABO-incompatible renal transplantation includes antigen-specific immunoadsorption (extracorporeal columns with the A or B trisaccharides), rituximab, and standard maintenance immunosuppression. Anti-A or -B titers ≤ 8 in the indirect antiglobulin test (IAT) against panel A1 or B RBC are acceptable for transplantation. CASE REPORT: A previously healthy, 15-month-old girl was diagnosed with Wilms' tumor and proteinuria. Denys-Drash syndrome was confirmed. Bilateral nephrectomy was performed. At 3.5 years of age she received an ABO-incompatible renal transplant from her father (A1 to O). The anti-A titers before transplantation were low. She was treated preoperatively with rituximab, immunoadsorption, immunoglobulin and mycophenolate mofetil (MMF). The maintenance immunosuppression protocol included basiliximab, tacrolimus, MMF, and prednisolone. The initial postoperative course was uncomplicated with rapid normalization of serum creatinine. The anti-A titers started to increase on postoperative day 5 (8 NaCl/16 IAT). Despite daily immunoadsorptions the titers rose to 1024 NaCl/1024 IAT on day 9. Renal function deteriorated and hemodialysis was started. A renal biopsy on day 9 showed acute severe antibody-mediated rejection. Additional treatment with bortezomib was given and after 2 doses the titers started to decline, renal allograft function improved and hemodialysis was stopped. On day 21 posttransplant the titers went down, creatinine was 28 µmol/L, and no more immunoadsorptions were performed. CONCLUSION: By using bortezomib, we were able to successfully reverse a severe ABO antibody-mediated rejection.

[Preventive bone mineral density measurement in postmenopausal women. Differentiation of treatment of recommendations Guidelines of the Umbrella Organization for Osteology ("Dachverband Osteologie")]. / Präventive Knochendichtemessung bei postmenopausalen Frauen. Differenzierung der Therapieempfehlungen der Leitlinien des Dachverbandes Osteologie (DVO).

BACKGROUND: Osteopenia (OP) or osteoporosis (OST) was diagnosed by bone densitometry (DXA) in postmenopausal women free of known skeletal disorders and without acute fracture. DVO guidelines were applied to define therapeutic indication. METHODS: The study included 94 women aged 59-81 years. Fracture or operation ≤12 months, malignant tumor, ovariectomy, and drugs such as cortisone, strontium, fluorides, bisphosphonates, SERMs, estrogens, and steroids were exclusion criteria. The lowest T-score at the spine, femoral neck, or total hip was decisive. The indication for therapy was determined by evaluating age, BMD, and other risk factors. RESULTS: Using the WHO criteria 22.3% (n=21) had normal BMD, 52.1% (n=49) had OP, and 25.6% (n=24) had OST. According to "Dachverband Osteologie" (DVO) guidelines, 28 women (29.8%) of the whole group needed therapy. Of the 28 women receiving therapy, 9 had OP and 19 had OST. Therapy was indicated in 18.4% for OP and 79.2% for OST. CONCLUSION: A preventive measurement of BMD with DXA provides a benefit for postmenopausal women. Combinatory assessment and consideration of other risk factors allows identification of women who might benefit from early treatment.

Expression of ATRAP in adipocytes and negative regulation by beta-adrenergic stimulation of JAK/STAT.

Sympatho-adrenergic activity and the renin-angiotensin system are considered critical regulators of obesity and hypertension. The novel angiotensin II type 1 receptor-associated protein (ATRAP) has been demonstrated to modulate angiotensin II signalling in smooth muscle cells and cardiomyocytes. Adipose tissue expresses important renin angiotensin system components and contributes to cardiometabolic disease. However, ATRAP expression and regulation in adipocytes are unknown. We investigated expression of this novel modulator of angiotensin signalling and its regulation by beta-adrenergic receptors. We found ATRAP to be expressed in differentiated brown and white adipocytes. Stimulation of beta-adrenoceptors strongly suppressed ATRAP expression. We hypothesised a role for JAK/STAT signalling elements. Indeed, beta3-adrenergic stimulation robustly stimulated both STAT1 and STAT3 phosphorylation in a time- and dose-dependent manner. This effect was abrogated by inhibition of PKA and JAK2 signalling. Moreover, inhibition of JAK/STAT and PKA signalling reversed the beta3-adrenergic suppression of ATRAP expression. This study provides the first evidence for expression and adrenergic regulation of the angiotensin II signalling modulator ATRAP in adipocytes. Further, it indicates a novel regulatory link between beta-adrenergic and JAK/STAT signalling.

[Comparison of central and peripheral corneal thicknesses between normal subjects and patients with primary open angle glaucoma, normal tension glaucoma and pseudoexfoliation glaucoma]. / Vergleich von zentraler und peripherer Hornhautdicke zwischen Normalprobanden und Patienten mit chronischem Offenwinkelglaukom, Normaldruckglaukom und Pseudoexfoliationsglaukom.

BACKGROUND: While many comparative data are available about central corneal thickness in different types of open angle glaucoma, peripheral corneal thickness has been much less investigated up to now. Thus, the aim of this study was to compare the central and peripheral corneal thicknesses in patients with primary open angle glaucoma (POAG), normal tension glaucoma (NTG) and pseudoexfoliation glaucoma (PEXG) to values of normal subjects. PATIENTS: 104 patients with POAG, 20 patients with NTG, 23 patients with PEXG and 127 normal subjects were investigated with the Orbscan II. The central corneal thickness and the peripheral corneal thickness at 3 mm distance from the centre were determined in 4 quadrants. The acoustic equivalent factor of 0.92 was not used. Patients with eye diseases, patients who had undergone eye surgery or wearers of contact lenses were excluded. Differences were analysed with the Bonferroni-adjusted Mann-Whitney U Test for statistical significance. RESULTS: The median central corneal thickness in POAG was 600 +/- 35 microm, in NTG 577 +/- 31 microm, in PEXG 603 +/- 25 microm and in the control group 606 +/- 38 microm. The difference between NTG and the control group was statistically significant (p = 0.01). Superiorly the peripheral corneal thickness was lower in POAG (670 +/- 47 microm) and NTG (639 +/- 37 microm) compared to the control group (686 +/- 46 microm). Nasally the peripheral corneal thickness was lower in POAG (656 +/- 48 microm), NTG (658 +/- 55 microm) and PEXG (642 +/- 47 microm) compared to the control group (677 +/- 46 microm). Temporally and inferiorly there were only small differences compared to the control group. The differences in peripheral corneal thickness were not statistically significant. DISCUSSION: In accord with literature data the central corneal thickness was lower in patients with normal tension glaucoma compared to normal subjects. Superiorly and nasally the peripheral corneal thickness was lower in patients with open angle glaucoma than in normal subjects which was, however, not statistically significant. To what extent these characteristics of the corneal architecture are relevant for the pathogenesis of open angle glaucomas has to be clarified in further larger trials.

Early recurrence of nephrotic syndrome (immunoglobulin m nephropathy) after renal transplantation successfully treated with combinations of plasma exchanges, immunoglobulin, and rituximab.

In contrast to focal segmental glomerulosclerosis, which is well known to recur early in a renal graft, there are only few cases described with recurrence of immunoglobulin M (IgM) nephropathy after transplantation. We herein describe a patient with early recurrence of IgM nephropathy. A 15-year-old boy with nephrotic syndrome (IgM nephropathy) proceeding to end-stage renal disease was on dialysis before living related renal transplantation. Native kidneys were not removed. Standard immunosuppression including steroids, tacrolimus, and mycophenolate mofetil yielded initially good graft function with the s-creatinine falling to 73 micromol/L. Proteinuria was present on day 1, increasing to 20 g/L after 3 days. S-creatinine increased to 158 micromol/L and urine production diminished. A graft biopsy showed no rejection or glomerulopathy but protein vacuoles were seen within tubular cells indicating massive proteinuria. Treatment with plasma exchanges, immunoglobulin, and steroids was started. Hemodialysis was necessary. Proteinuria improved to 3.5 g/L, but s-creatinine continued to rise and a second graft biopsy showed vascular rejection (Banff type IIA). The patient was treated with antithymocyte globulin and further plasma exchanges. A single dose of rituximab was given. Five months after transplantation the s-creatinine was 67 micromol/L and there was no proteinuria. In this case early recurrence of nephrotic syndrome occurred on the first posttransplant day in combination with later occurring vascular rejection. Successful treatment included a combination of plasma exchanges, rituximab, immunoglobulin, and antithymocyte globulin.

Molecular remission of CML after autotransplantation followed by adoptive transfer of costimulated autologous T cells.

Four patients with chronic myelogenous leukemia (CML) that was refractory to interferon alpha (two patients) or imatinib mesylate (two patients), and who lacked donors for allogeneic stem cell transplantation, received autotransplants followed by infusions of ex vivo costimulated autologous T cells. At day +30 (about 14 days after T-cell infusion), the mean CD4+ cell count was 481 cells/microl (range 270-834) and the mean CD8+ count was 516 cells/microl (range 173-1261). One patient had a relative lymphocytosis at 3.5 months after T-cell infusion, with CD4 and CD8 levels of 750 and 1985 cells/microl, respectively. All the four patients had complete cytogenetic remissions early after transplantation, three of whom also became PCR negative for the bcr/abl fusion mRNA. One patient, who had experienced progressive CML while on interferon alpha therapy, became PCR- post transplant, and remained in a molecular CR at 3.0 years of follow-up. All the four patients survived at 6, 9, 40, and 44 months post transplant; the patient who remained PCR+ had a cytogenetic and hematologic relapse of CML, but entered a molecular remission on imatinib. Autotransplantation followed by costimulated autologous T cells is feasible for patients with chronic phase CML, who lack allogeneic donors and can be associated with molecular remissions.

Multiple and synergistic deregulations of apoptosis-controlling genes in pancreatic carcinoma cells.

Inability to die by apoptosis is one of the reasons for the deregulated growth of tumour cells and the frequently observed failure of chemotherapy. In this study we thought to identify the common and functionally important characteristics responsible for the apoptosis resistance of pancreatic tumour cells. We analysed cell surface expression level of death receptors CD95 and TRAIL-R1-4 as well as the expression profile of sixteen apoptosis-relevant proteins in five pancreatic carcinoma cell lines Capan1, Colo357, PancTuI, Panc89 and Panc1. These data were evaluated in the context of sensitivity towards anti-CD95 and TRAIL-mediated apoptosis. Here we report that except for resistant Panc1 cells, which only marginally expressed CD95, all other cell lines showed comparable levels of CD95 and TRAIL receptors irrespectively of their apoptotic phenotype. Interestingly, we found that the elevated expression of FLIP, Bcl-x(L) and IAP in parallel with a downregulation of FADD and Bid was common for the resistant cell lines. Consequently, stable overexpression of XIAP, Bcl-x(L) or dominant negative FADD in sensitive cells significantly reduced the death receptor mediated apoptosis while the overexpression of Bid rendered the resistant cells sensitive.

Influence of preapheresis clinical factors on the efficiency of CD34+ cell collection by large-volume apheresis.

We evaluated 120 leukapheresis procedures (93 patients), in order to detect clinical factors that influence the efficiency of CD34+ collection using Cobe Spectra trade mark cell separators. Hematocrit was >27% and platelet count >30 000/microl in >95% of patients. Platelet transfusions were given if the postprocedure count was &<20 000/microl. Multiple regression analysis was used to analyze putative factors, and a predictive equation defined by stepwise regression modeling. The mean efficiency was 0.59 (s.d. 0.27). Sex (M>F; P=0.01), the volume processed (inversely; P=0.01) and CD34+ cell count (inversely; P=0.04) were associated with efficiency, whereas hematocrit, platelet or leukocyte count, catheter type and patient weight were not. The effect size for predictive factors was small (R(2)=0.21). Adverse events were limited to hypocalcemia. We conclude that female sex, volume processed and CD34+ cell count adversely influence the efficiency of CD34+ cell leukapheresis. However, the impact of volume and CD34+ cell count is small, and likely to be offset by the influence of these same factors on overall yield. Leukapheresis appears to be safe and efficient for autologous blood and marrow transplantation patients with hematocrit >27% and platelet count >30 000/microl.

Treatment of paediatric pontine glioma with oral trophosphamide and etoposide.

To evaluate the overall survival of paediatric patients with pontine gliomas treated with oral trophosphamide and etoposide. Patients between 3 and 17 years of age with either typical diffuse pontine glioma on MRI or histologically proven anaplastic astrocytoma/glioblastoma multiforme located in the pons, were eligible. Treatment consisted of oral trophosphamide 100 mg x m(-2) x day(-1) combined with oral etoposide at 25 mg x m(-2) x day(-1) starting simultaneously with conventional radiation. Twenty patients were enrolled (median age 6 years, male : female=9 : 11). Surgical procedures included: no surgery: five, open biopsy: three, stereotactic biopsy: six, partial resection: three, and sub-total resection: three. Histological diagnoses included pilocytic astrocytoma: one, astrocytoma with no other specification: three, anaplastic astrocytoma: three, glioblastoma multiforme: eight, no histology: five. The most frequent side effects were haematologic and gastrointestinal. There was no toxic death. The response to combined treatment in 12 evaluable patients was: complete response: 0, partial response: three, stable disease: four, and progressive disease: five. All tumours progressed locally and all patients died. The overall median survival was 8 months. The overall survival rates at 1 and 4 years were: 0.4 and 0.05 respectively. This was not different from a control group of patients documented in the same population. Oral trophosphamide in combination with etoposide did not improve survival of pontine glioma patients. The treatment was well tolerated and should be evaluated for more chemoresponsive paediatric malignancies.

An improved method for the rapid assessment of persisting chylomicron remnant concentrations.

Persisting chylomicron remnant concentrations have been linked to premature atherosclerosis. The analysis of persisting chylomicron remnant concentrations by an oral triglyceride tolerance test, however, is time-consuming for the study subjects and requires large resources in the laboratory. Therefore, only small numbers of subjects have been studied in the past. We describe major improvements of the testing procedure in regard of composition of the fatty meal, of patient testing, and measurement of postprandial remnants. Shifting the time of the (ready-to-use) fatty drink from the morning hours to bedtime was well accepted by the study subjects and allowed the analysis of blood samples drawn at the morning with minimal impact on the participants' time and with minimal interferences by confounding factors (e.g. smoking, additional food intake, physical activity). Chylomicron remnants were measured by fluorometry of the supernatant after ultracentrifugation. This procedure was sensitive, was specific for chylomicron remnants, and was easy to perform. The biological validity of the improved procedure was evaluated by studying type III hyperlipoproteinemia patients and normolipemic apolipoprotein (Apo) E2 homozygotes. In conclusion, this improved test permits the rapid testing for persisting chylomicron remnants in the clinical routine and in large epidemiological studies.

Effects of fenofibrate and gemfibrozil on plasma homocysteine.

Fenofibrate increases plasma homocysteine. Because the concentration of plasma homocysteine depends on renal function, we postulate that increases in plasma homocysteine are a result of the known impairment of renal function caused by fenofibrate. Gemfibrozil, another fibrate, does not affect renal function. In a crossover study we tested whether gemfibrozil would raise homocysteine. 22 patients who had hypertriglyceridaemia were given 900 mg gemfibrozil or 200 mg fenofibrate daily for 6 weeks. Lipids were altered similarly, but homocysteine, creatinine, and cystatin C were raised by fenofibrate but not by gemfibrozil (p for differences between treatment effects: 0.007, 0.006, and 0.040, respectively). We propose gemfibrozil should be the fibrate of choice.

Factors explaining the difference of total homocysteine between men and women in the European Investigation Into Cancer and Nutrition Potsdam study.

Interestingly, plasma total homocysteine (tHcy) concentration is consistently higher in men than in women. This observation deserves further investigations because elevated tHcy concentrations have been shown to be independently associated with coronary, peripheral, and cerebral vascular diseases. It was the aim of the present study to define major determinants of plasma tHcy in a healthy middle-aged German population under particular consideration of the gender factor. The study population was obtained from an ongoing recruitment procedure for a cohort study and comprised 336 men and women, aged 40 to 65 years. Exclusion criteria were elevated creatinine levels in blood, history of skin or atherosclerotic diseases, current use of vitamins or other supplements, and heavy smoking. Plasma tHcy, folate, vitamin B12, vitamin B6, creatinine, testosterone and estradiol, protein, and hematocrit were measured. Fat-free mass was assessed by skinfold thickness. The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR), a key enzyme of folate and homocysteine metabolism, was determined by polymerase chain reaction (PCR) with restriction enzyme analysis. In this population, plasma tHcy ranged from 5 to 46 micromol/L. The frequency of the T allele of the MTHFR was 0.29, which is lower than in other populations. A total of 54.2% of this population was homozygote for the wild-type, 39.6% heterozygote, and 6.2% homozygote for the mutation. tHcy correlated negatively with folate and cobalamin concentration in blood and positively with creatinine. No correlation was seen with vitamin B6. From the gender-related variables, tHyc correlated significantly with fat-free mass and testosterone and inversely with estradiol. The difference between gender with regard to tHcy was mainly explained by differences in fat-free mass, but also by estradiol concentrations. The following contributions to the variation of tHcy were seen in a multivariate regression model: plasma cobalamin (11%), creatinine (11%), plasma folate (8%), fat-free mass (5%), estradiol (2%), MTHFR polymorphisms (2%), and plasma protein (1%). We concluded that tHcy in the general population has a variety of determinants ranging from nutrition, internal metabolic parameters to gender-related variables.

Oral trofosfamide and etoposide in pediatric patients with glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme in childhood is rare, and the prognosis for patients with the disease is poor. The Pediatric Oncology Society of the Germanic language group (GPOH) enrolls patients in a series of pilot trials, the first of which is reported here (HIT-GBM-A). METHODS: Twenty-two patients with glioblastoma multiforme, World Health Organization Grade 4, between the ages of 3-15 years (45% male) were enrolled during the period 1995-1997. There were 13 supratentorial tumors, 8 brainstem tumors, and 1 cerebellar tumor. The patients underwent the following procedures: stereotactic biopsy (n = 3 patients), open biopsy (n = 1 patient), partial resection (n = 6 patients), subtotal resection (n = 4 patients), and macroscopic total resection (n = 8 patients). Adjuvant treatment consisted of oral chemotherapy with trofosfamide, 100 mg/m(2), and etoposide, 25 mg/m(2), daily or for 21-day cycles interrupted by 1-week rests. Standard fractionated radiation (54 grays) was started concurrently with the first cycle. RESULTS: The chemotherapy was well tolerated, with no treatment-related deaths and only minor side effects. The responses in 12 evaluable patients after two cycles were as follows: 1 complete response, 1 partial response, 3 patients with stable disease, and 7 patients with progressive disease. The median overall survival was 12 months. The 1-year, 2-year, and 4-year overall survival rates were 52%, 26%, and 22%, respectively, and the event free survival rates were 26%, 22%, and 4%, respectively. None of the four surviving patients (3.2 years, 3.4 years, 4.0 years, and 4.2 years after diagnosis) is event free. Two patients are alive after tumor progression: One patient was diagnosed with a medulloblastoma, and one patient was diagnosed with an osteosarcoma as second malignancies. A control group extracted from the Surveillance, Epidemiology, and End Results data had lower survival rates: the difference between the groups was not statistically significant (P = 0.26). CONCLUSIONS: This chemotherapy will not be used in a randomized trial of patients with glioblastoma; however, it may be evaluated for patients with tumors that have more chemoresponsive histologies.

Concurrent diagnosis of acromegaly and diabetic ketoacidosis.

OBJECTIVE: To report the occurrence of diabetic ketoacidosis (DKA) in a patient with acromegaly. METHODS: A case report with clinical and laboratory details is presented, and the few other cases of DKA and acromegaly from the literature are discussed. RESULTS: A 37-year-old man requested a consultation because of nausea, vomiting, polydipsia, polyuria, and weight loss. Physical examination revealed findings suggestive of acromegaly, including coarse facial features and enlargement of his hands and feet. Laboratory studies confirmed the diagnoses of DKA and acromegaly. Magnetic resonance imaging disclosed the presence of a pituitary adenoma, which was subsequently removed surgically. Although the DKA had been managed with insulin therapy, 2 weeks postoperatively the insulin dose was tapered and then discontinued because of hypoglycemia. Follow-up showed normalization of growth hormone levels and plasma glucose levels. Only three other cases of DKA associated with acromegaly were found in the medical literature. CONCLUSION: Although DKA is rarely diagnosed in conjunction with acromegaly, this unusual association was confirmed in the current patient.

Serum homocysteine increases after therapy with fenofibrate or bezafibrate.

A 44% and 17.5% increase of homocysteine occurred in patients treated either with fenofibrate or bezafibrate. The increase was not explained by changes in vitamin concentrations but may be related to renal function.

Diagnostic relevance of interleukin pattern, acute-phase proteins, and procalcitonin in early phase of post-ERCP pancreatitis.

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has been suggested as a model for acute pancreatitis (AP), which allows evaluation of early alterations in the time course of the disease. The influence of the clinical course on procalcitonin (PCT), serum amyloid A (SAA), and several proinflammatory and inhibitory cytokines was evaluated in patients with AP following ERCP. Blood samples were prospectively collected from patients undergoing ERCP. The incidence of ERCP-induced pancreatic damage, defined as abdominal complaints, a threefold increase of serum lipase, and elevation of CRP from <10 to >20 mg/liter was 12.8% (12/94). Only mild clinical courses of acute pancreatitis were observed. PCT significantly increased in subjects with post-ERCP pancreatitis after 24 hr. However, PCT levels did not exceed 0.5 ng/ml in any patient. Interleukin-1 receptor antagonist (IL-1RA) began to differ from baseline 2 hr after ERCP, followed by interleukin-6 (IL-6, 6 hr), solubilized tumor necrosis factor-alpha receptor II (sTNF-alphaRII, 24 hr) and SAA (24 hr). Interleukin 10 (IL-10) showed marked interindividual variations with no obvious peak. Among all parameters evaluated, only peak values of IL-6 and IL-10 showed significant correlations with the reported pain score (r2 = 0.62/0.78), degree of ampullar irritation (r2 = NS/0.87), and the duration of ERCP (r2 = 0.58/0.76). No correlation was found with the volume of the injected contrast agent. We conclude that IL-10 and IL-6 appear to be useful to monitor patients after ERCP. The absence of any PCT elevation in the present study is in accordance with the clinical course of the patients who suffered from mild pancreatic damage without systemic or infectious complications.

Compositional and functional changes of low-density lipoprotein during hemodialysis in patients with ESRD.

BACKGROUND: This study focused on the effects of hemodialysis on the atherogenic properties of low density lipoprotein (LDL) in patients with end-stage renal disease (ESRD). The impact of cholesterol ester transfer protein (CETP) activity and lipolysis on LDL composition, particularly the changes during hemodialysis, was investigated. METHODS: Blood was drawn from 15 normotriglyceridemic (NTG) and 15 hypertriglyceridemic patients [HTG; triglycerides (TG) < 2.2 mmol/liter] before hemodialysis, during (1.5 hr after the beginning of anticoagulation) and at the end of treatment. In each sample, lipid values and CETP activity were measured. LDL was prepared and characterized by its components and diameters (2 to 16% PAGGE). To investigate the functional properties of LDL, fractions obtained from NTG and HTG patients were incubated with human skin fibroblasts and a cell line of murine macrophages (P388), and cholesterol ester formation rates were measured. RESULTS: In comparison to LDL from NTG patients at baseline, HTG-LDL were enriched in triglycerides (P < 0.02), depleted in cholesterol proportion (P < 0.01) and small in size (P < 0.001). These LDL induced the cholesterol esterification rates (50 micrograms/mL LDL-protein) in a twofold greater unsaturation in macrophages when compared to LDL from NTG patients (P < 0.04). The rates in fibroblasts were reduced by approximately half (P < 0.05). During hemodialysis, LDL were decreased in size (P < 0.001) and depleted in TG (P < 0.01), particularly in the hypertriglyceridemic state. Although CETP activity increased during hemodialysis (P < 0.001), the cholesterol content remained unchanged. When HTG-LDL obtained during hemodialysis were incubated with cells, esterification rates particularly in macrophages were markedly accelerated in comparison to the unmodified lipoprotein at baseline (P < 0.05). CONCLUSION: LDL from HTG patients with ESRD was TG-enriched, CH-depleted and smaller in size. As the intracellular esterification rates induced by LDL were related to the cellular uptake, these LDL were a superior substrate for murine macrophages with the tendency of intracellular accumulation, and an inferior substrate for fibroblasts suggesting a decreased uptake by the specific receptor pathway. TG-depletion of LDL during hemodialysis, particularly in HTG patients due to a lipase-mediated TG-hydrolysis, increased these effects in macrophages. We suggest that the alterations of LDL that occur during repeated hemodialysis in vivo could contribute to the high prevalence of premature atherosclerosis found in HTG patients with ESRD.