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D Seidel

Publications and source records attributed to D Seidel.

At least 19 recordsLinked to original sources
PubMed2005

Apoptosis and release of CD44s in bleomycin-treated L132 cells.

The anti-cancer drug bleomycin (BLM) induces lung injury and triggers apoptosis of alveolar epithelial cells. In epithelia, among other functions, the adhesion protein CD44 promotes the contact to components of the extracellular matrix like hyaluronate. A functional link between apoptosis and the loss of CD44 has been observed in colon carcinoma cells and involvement of CD44 in apoptosis of lung cells has been reported in several studies. The present in vitro study examined the expression of CD44s (CD44 standard) in two human epithelial lung cell lines, L132 and A549, during BLM-induced apoptosis. A loss of CD44s by lung epithelial cells and an increase of the soluble form of this adhesion protein in culture supernatants upon exposure to BLM were observed. Apoptosis was characterized by an activation of caspase-3 as well as by release of cytochrome C into the cytosol as shown for L132 cells. Inhibition of apoptosis by the broad-range caspase inhibitor Z-VAD-fmk reduced CD44 release by both cell lines demonstrating that CD44 release is a result of apoptotic processes. Kinetic experiments failed to discriminate between the initiation of apoptosis and CD44 release. Blocking experiments using antagonistic anti-CD95 receptor antibodies revealed that BLM may cause apoptosis and CD44 release in a CD95-independent manner.

Apoptosis↗
PubMed2005

Quantum kinetic energy densities: an operational approach.

We propose and investigate a procedure to measure, at least in principle, a positive quantum version of the local kinetic energy density. This procedure is based, under certain idealized limits, on the detection rate of photons emitted by moving atoms which are excited by a localized laser beam. The same type of experiment, but in different limits, can also provide other non-positive-definite versions of the kinetic energy density. A connection with quantum arrival time distributions is discussed.

Journal Article↗
PubMed2005

Partial liquid ventilation in acute salt water-induced lung injury.

BACKGROUND AND OBJECTIVES: Salt-water aspiration results in pulmonary oedema and hypoxia. We tested the hypothesis that partial liquid ventilation has beneficial effects on gas exchange and rate of survival in acute and extended salt water-induced lung injury. METHODS: Anaesthetized, ventilated rats (tidal volume 6 mL kg(-1), PEEP 5 cmH2O) received a tracheal salt-water instillation (3%, 8 mL kg(-1) body weight) and were randomly assigned to three groups (n = 10 per group). While lungs of Group 1 were gas-ventilated, lungs of Group 2 received a single perfluorocarbon instillation (30 min after the injury, 5 mL kg(-1) perfluorocarbon) and lungs of Group 3 received an additional continuous perfluorocarbon application into the treachea (5 mL kg(-1) h(-1)) Arterial blood gases were measured with an intravascular blood gas sensor. RESULTS: Salt-water instillation resulted in a marked decrease in PaO2 values within 30 min (from 432 +/- 65 to 83 +/- 40 mmHg, FiO2 = 1.0, P < 0.01). Arterial oxygenation improved in all three groups irrespective of treatment. We observed no significant differences between groups in peak PaO2 and PaCO2 values. CONCLUSIONS: Our results suggest that partial liquid ventilation has no additional beneficial effects on gas exchange after life-threatening salt water-induced lung injury when compared to conventional gas ventilation with positive end-expiratory pressure.

Anesthesia↗
PubMed2005

Rosiglitazone plus metformin is effective and well tolerated in clinical practice: results from large observational studies in people with type 2 diabetes.

This study investigated the efficacy during daily practice of rosiglitazone (RSG) added to metformin (MET) in poorly controlled type 2 diabetes mellitus. Two post-marketing observational studies were conducted in Germany over 6 months. RSG (4 mg/day titrated to 8 mg/day as required) was added to existing MET in 11,014 subjects. Subjects were maintained on diet and exercise. Addition of RSG to MET significantly reduced median HbA 1c by 1.3% (8.1 vs. 6.8%; p < 0.0001) and median fasting blood glucose (FBG) by 47.0 mg/dl (171.0 vs. 124.0 mg/dl; p < 0.0001) after 6 months. The proportion of subjects achieving HbA(1c) targets of < or = 6.5 and < or = 7.0% increased from 3.5 to 38.8% and from 13.5 to 63.7%, respectively. Mean systolic and diastolic blood pressure decreased by 7 and 3 mmHg, respectively (p < 0.0001). Mean weight decreased by 1.7 kg and was constant or reduced in most (74.1%) subjects. Addition of RSG to MET significantly reduces median HbA 1c and FBG in clinical practice and is generally well tolerated.

Aged↗
PubMed2004

Early signs of lung fibrosis after in vitro treatment of rat lung slices with CdCl2 and TGF-beta1.

Precision-cut rat lung slices have been employed in combination with an extensive immunohistochemistry of paraffin-embedded slices for monitoring of early pathohistological changes after exposure to CdCl(2)/TGF-beta(1). Three days of CdCl(2) exposure in combination with TGF-beta(1) seem to be sufficient to induce lung injury with alterations similar to changes observed in early lung fibrogenesis: (1) extracellular matrix accumulation and myofibroblast transdifferentiation (Sirius red staining, collagen type IV, alpha-smooth muscle actin), (2) type I cell injury with loss of type I cell antigens (T1alpha antigen, aquaporin-5, RAGE), (3) increased apoptosis of pulmonary cells (active caspase-3, vimentin cleavage product V1 of caspase-9), and (4) activation of microvascular endothelial cells (podocalyxin, caveolin-1). Western blot analysis confirmed the increasing amount of alpha-smooth muscle actin, the loss of T1alpha antigen, and the increase in caveolin-1 immunoreactivity. The explant culture using CdCl(2)/TGF-beta(1) provides a suitable tool for the study of other factors involved in pulmonary pathology including transcription factors, cytokines, and other metabolites involved in early stages of fibrogenesis.

Actins↗
PubMed2004

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Clinical Trials as Topic↗
PubMed2003

[Coronary heart disease in childhood in familial hypercholesteremia. Maximum therapy with LDL apheresis].

In children with familial hypercholesterolemia, coronary heart disease requires both medical theraphy and LDL apheresis. We report a case of verified occlusion of the anterior descending branch of the left coronary artery in a 10-year-old patient. The pathological findings revealed by ergometry established the diagnosis. The goal was to achieve the greatest possible reduction of lipid parameters and fibrinogen by lowering plasma viscosity employing LDL apheresis. It is astonishing that this treatment is also well tolerated by children. The basic vascular approaches suffice and shunt operations are not absolutely necessary. The efficacy of this method became vividly apparent by the changes in the skin lesions. Additional angiographic follow-up and further clinical course wil provide information on the usefulness of this treatment strategy with maximum lipid theraphy and the expected improvement in prognosis.

Anticholesteremic Agents↗
PubMed2003

[LDL-apheresis in the treatment of coronary heart disease. Rationale for a specific adjuvant therapy].

Coronary artery disease (CHD) still remains the leading cause of death in all industrialized countries. In Germany, it claims the lives of an estimated 220,000 men and women and causes 200,000 non-lethal AMI's each year. Inspite of great efforts in the last 30 years, 25% of men and 40% of women still die within 12 months after they preliminary survived their first myocardial infarction. The total direct plus indirect expenses for CHD in the year 2000 sum up to approximately 57 billion Euro in Germany and to 100 billion US $ in the US. To date, management of coronary artery disease still consists mainly of a therapy designed to improve blood flow and oxygen supply to the heart or to reduce myocardial oxygen consumption. On this line angioplasty, bypass surgery, and more recently stenting of coronary arteries, have become leading techniques, but only a minority (<50%) of patients at risk for CHD received therapy to change the atherosclerotic process itself. However, only by means of a causal intervention with the pathmaker mechanism of atherosclerosis can we expect to decrease the financial burden of CHD. No question, one of the leading causal factors for early atherosclerosis and coronary heart disease is the abundance of LDL cholesterol in the blood, exceeding limits of 100 mg/dl. Thus, recommendations for therapy focus on LDL levels less than 100 mg/dl. With the introduction of the statins-a family of very potent lipid lowering agents-such target levels can be achieved in most patients, resulting in a drastic decrease of LDL concentrations, as well as in a reduction of cardiac and total mortality. There is, however, a remaining small group of patients, who are more or less resistant to an adequate combination of dietary and drug therapy. For these patients, various techniques of apheresis have been available for over 15 years. Some of them, e. g., H.E.L.P. System, KANEKA System, have been approved by the FDA in the US and comparable regulatory offices in Europe. The most extensive experimental and clinical experience was gathered with the H.E.L.P. System by B. Braun Melsungen, which differs from other apheresis techniques by its efficiency to eliminate LDL, Lp(a), fibrinogen and CRP simultaneously. The clinical results obtained to date with the H.E.L.P.-LDL-apheresis clearly demonstrate a significant reduction of risk factors and clinical events, as well as an excellent long-term tolerance. A comprehensive literature survey on H.E.L.P. is part of this communication.

Anticoagulants↗
PubMed2003

[Prevention of early graft occlusion after coronary bypass grafting by post-operative reduction of plasma fibrinogen by H.E.L.P. apheresis. First evaluation of 12 patients treated during our study (44 bypasses)].

BACKGROUND: Early graft occlusion is a known complication after CABG (Coronary Artery Bypass Grafting). The thromboembolic closure of the bypass occurs at a frequency of 5-15%, depending on the implemented vessel (arterial or venous graft). Fibrinogen as a substrate of thrombus formation plays a major role in both primary and secondary haemostasis. The operative trauma triggers the acute phase-response and also activates the clotting process. This leads to high fibrinogen levels of up to 600 mg/dl postoperatively, providing an impaired haemorrheological pattern which promotes thrombus formation. In a prospective pilot-study we examined whether drastic postoperative lowering of fibrinogen by H.E.L.P.-(Heparin-mediated Extracorporeal LDL-/Fibrinogen Precipitation) apheresis can prevent early graft vessel closure in patients undergoing CABG. METHODS: For the purpose of this study 12 male patients (mean age 60+/-5.8 years) who underwent multivessel CABG were recruited between 12/2000 and 2/2002 according to a GCP approved protocol. The postoperative fibrinogen levels of the patients were monitored and H.E.L.P. apheresis was applied when plasma fibrinogen levels exceeded >350 mg/dl on day 1 and >250 mg/dl every following day up to day 8 after the operation. Pre- and post apheresis blood samples were obtained and reduction of plasma fibrinogen, LDL-Cholesterol and CRP were determined. Coronary angiography was performed within the 9th-16th postoperative day. To investigate the long term outcome a second coronary angiography was performed half a year after the operation. RESULTS: A total of 44 bypass grafts (23 arterial; 21 vein grafts) were implemented in 12 patients (mean 3.6/patient) and a total of 66 H.E.L.P.-Apherses from day 1-8 were postoperatively applied (mean 5.5/patient). Fibrinogen levels were lowered from a maximum on day 2 of 447+/-112.2 mg/dl (pre-apheresis) to a minimum on day 8 of 228+/-46.2 mg/dl (pre-apheresis) demonstrating a reduction of 50%. Per single treatment the fibrinogen was lowered from 357+/-93 mg/dl (pre-apheresis) to 157+/-46 mg/dl (post apheresis); reduction: 55%. Coronary angiography revealed graft patency in 43 of 44 grafts (97.7% patency). The one occluded bypass was an Y-graft to a diagonal branch less than 1mm in diameter. No bleeding or H.E.L.P. related complications were observed.Up to now 7 of 12 patients underwent the second coronary angiography according to the study protocol. Apart from the already immediately postoperatively occluded Y-graft no new bypass-occlusion was revealed. CONCLUSIONS: Early and extensive reduction of postoperatively elevated plasma fibrinogen levels by H.E.L.P. apheresis seems to be an efficient and safe therapeutic approach for preventing early graft occlusion in patients undergoing multivessel CABG.

Anticoagulants↗
PubMed2003

[Treatment of sudden hearing loss through Fibrinogen/LDL-apheresis. A prospective, randomized multicenter trial].

INTRODUCTION: Sudden sensorineural hearing loss (SSHL) is thought to be of various origins. Disturbances of microcirculation, autoimmune pathology and viral infection are among the most likely causes. Acute reduction of plasma fibrinogen and serum LDL positively influences hemorheology and endothelial function and might thus be an effective therapy for SSHL. OBJECTIVE: To test the hypothesis that fibrinogen/LDL-apheresis is as effective or superior to conventional therapy with plasma expanders and prednisolone in the treatment of SSHL. DESIGN: controlled, prospective, randomized, multicenter trial. SETTING AND PATIENTS: 201 patients were recruited from 01/2000 to 6/2001 at the University Clinics of Munich, Berlin, Hamburg and Bochum. Inclusion criteria was sudden sensorineural hearing loss of unknown origin within 6 days of onset. INTERVENTIONS: Single fibrinogen/ LDL-apheresis infusion of prednisolone (250 mg, tapered by 25 mg daily), hydroxyethyl starch (500 ml, 6%) and pentoxifylin (400 mg/day). MAIN OUTCOMES: Improvement of pure tone thresholds 48 h after onset of therapy. RESULTS: Over all improvement of pure tone thresholds in the fibrinogen/ LDL-apheresis treated patients is slightly but not significantly better than in the standard therapy group. After 48 h, 50% speech perception in the fibrinogen/ LDL-apheresis group (21.6+/-20.1 dB) is significantly (p<0.034) better than in the standard group (29.3+/-29.4 dB). Patients with plasma fibrinogen levels of more than 295 mg/dl have a substantial and significantly (p<0.005) better improvement of speech perception (15.3+/-17.3 dB) than standard treated patients (6.1+/-10.4 dB). CONCLUSIONS: Fibrinogen/LDLapheresis is at least equally effective compared to prednisolone treatment in sudden hearing loss. Selected patients with plasma fibrinogen of more than 295 mg/dl improve significantly better when treated with fibrinogen/LDLapheresis.

Adolescent↗
PubMed2003

Cathepsins in bleomycin-induced lung injury in rat.

Endogenous inhibitors tightly control the activity of proteinases in the extracellular space. Proteinase/antiproteinase imbalance may be caused by predominance of proteinases, resulting in severe tissue damage or abundance of proteinase inhibitors, leading to a shift in the balance of synthesis and degradation of extracellular matrix proteins and accumulation of these matrix components. Lung fibrosis is characterised by accumulation of fibrous matrix proteins in the alveolar interstitium. The activity of cathepsin D and amounts of cathepsins D and B in bleomycin-injured rat lung tissue and alveolar macrophages were examined. In addition, the activities of cathepsins and cysteine proteinase inhibitors (CPIs) in bronchoalveolar lavage fluid (BALF) were determined. No cathepsin but high CPI activity and large amounts of procathepsin B were detected in the BALF. In the alveolar lumen, the disturbed proteinase/antiproteinase balance for cysteine proteinases was clearly dominated by CPIs. In alveolar macrophages, the main source of increased cathepsin levels, large changes in cathepsin B and D content were observed during the inflammatory phase, corresponding to the occurrence of procathepsin B in BALF. With the end of the phase of tissue remodelling, imbalances in cathepsin and CPI activities were largely eliminated. Immunoblot data, revealing an increase in cathepsin D levels in myofibroblast-like cells compared to fibroblasts and in resting fibroblasts compared to proliferating cells, implicate this proteinase in the differentiation and conversion processes occurring at the beginning of the fibrotic phase of lung injury. The results show that cathepsin amounts and activities are increased transiently in lung tissue during regeneration processes in bleomycin-induced lung injury. Imbalances of cathepsin and cysteine proteinase inhibitors activities are also a phenomenon of the phase of tissue remodelling initiated by lung injury.

Animals↗
PubMed2002

Serum CEA and CA 15-3 as prognostic factors in primary breast cancer.

In the present study, we investigated the association of the serum levels of the tumour markers carcinoembryonic antigen and cancer antigen 15-3 with disease free survival and death from disease in 1046 women with breast cancer without metastases at the time of primary diagnosis in relation to age and the established prognostic factors tumour size, lymph node status, histological grading and hormone receptor status. We found that elevated pre-operative serum marker values were correlated with early relapse (cancer antigen 15-3; P=0.0003) and death from disease (carcinoembryonic antigen, cancer antigen 15-3; P=0.0001 both) in univariate analyses. By comparing pre- and post-operative values we found a decline in values post-surgery. In those patients where marker levels of carcinoembryonic antigen decreased more than 33%, a significantly higher risk for relapse and death from disease (both P=0.0001) in univariate analyses was observed. In multivariate analysis this decrease of carcinoembryonic antigen proved to be an independent prognostic factor. The results for cancer antigen 15-3 were comparable to carcinoembryonic antigen in univariate analyses but showed no significance in multivariate analysis. In this study the post-operative decrease of the serum tumour marker carcinoembryonic antigen was a strong independent prognostic factor for disease free survival and death from disease in breast cancer patients.

Breast Neoplasms↗
PubMed2002

Pharmacokinetics of pravastatin in heart-transplant patients taking cyclosporin A.

BACKGROUND: Heart transplantation is an established tool for the treatment of terminal heart failure. Hyperlipidemia is a common problem following heart transplantation and has been implicated as an additional risk factor in the development of transplant coronary artery disease (TxCAD). Therefore, heart recipients are commonly treated with inhibitors of cholesterol synthesis (HMG-CoA reductase inhibitors). However, these patients have an increased risk of developing rhabdomyolysis due to elevated concentrations of HMG-CoA reductase inhibitors under co-administration with the immunosuppressive cyclosporin A (CsA). AIM OF THE STUDY: Aim of our study was to obtain pharmacokinetic data on pravastatin whilst monitoring the safety and efficiency of the lipid lowering therapy in heart-transplant recipients under immunosuppression with CsA and to compare these data to those of a healthy control group. SUBJECTS, MATERIALS AND METHODS: Eleven patients (30.2 +/- 12.3 months after transplantation) receiving immunosuppressive therapy consisting of cyclosporin A, prednisone and azathioprine with LDL cholesterol (LDL-C) concentrations exceeding 3.9 mmol/l and 8 control subjects were included into the study. In addition to the immunosuppressive therapy, the patients received a daily dose of 40 mg/day pravastatin for the first 8 days which was then reduced to 10 mg/day administered until Day 29. Blood was sampled for pharmacokinetic profiling (maximum concentration of the drug (Cmax), time to reach Cmax (tmax), area under the concentration vs. time curve (AUC(0-24h)), elimination half-life time (tcl)) and measurement of the parameters of clinical chemistry on Days 1, 8 and 29. The control group received a single dose of 60 mg pravastatin and the values of Cmax and AUC(0-24h) were normalized for a dose of 10 mg. RESULTS: Pravastatin 40 mg/day for 1 week in the patient group caused a significant reduction in total cholesterol (C) and LDL-C from 8.11 +/- 1.20 mmol/l and 5.88 +/- 1.15 mmol/l to 6.91 +/- 1.01 mmol/l and 4.72 +/- 1.05 mmol/l, respectively (p = 0.005 and p = 0.003). Triglycerides and HDL cholesterol (HDL-C) concentrations did not change significantly. Mean values for Cmax of pravastatin were 384.2 ng/ml, 392.0 ng/ml and 115.1 ng/ml in patients on Days 1, 8 and 29, respectively. After normalization for a dose of 10 mg, the corresponding values of C(max-DN10mg) and Cmax were 96.0 ng/ml, 98.0 ng/ml and 115.1 ng/ml on study Days 1, 8 and 29. These values were 7-8 times higher than the normalized value of C(max-DN10mg) for the control group (13.7 ng/ml). The corresponding values of AUC(0-24h) were 1228.2 ng/ml x h, 1214.1 ng/ml x h and 345.9 ng/ml x h in the patient group on study Days 1, 8 and 29 as well as 157.5 ng/ml x h in the control group prior to normalization. After normalization for a dose of 10 mg, the values of AUC(0-24h-DN10mg) in the patient group were approximately 12 times higher than those of the control group. However, no significant differences between the 2 groups were observed in tmax and tcl. Within the patient group, no significant increase in Cmax or AUC was found on Day 1 to Day 8. The results of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) showed also no significant increase during the observation period. CONCLUSION: Heart-transplant recipients treated with the HMG-CoA reductase inhibitor pravastatin generally show higher plasma concentrations of this drug than control subjects. However, our data suggest that the HMG-CoA reductase inhibitor pravastatin can be used effectively in these patients receiving the immunosuppressive cyclosporin A. The pharmacokinetic data obtained indicate that there is no significant cumulation of the drug following multiple dosages in spite of increased drug concentrations after a single oral dosage.

Anticholesteremic Agents↗
PubMed2001

Nucleosomes in serum of patients with benign and malignant diseases.

High quantities of mono- and oligonucleosomes circulate in the blood of patients with malignant tumors. For their direct quantification in serum, we modified the Cell Death Detection(plus)-ELISA for its application in liquid materials. We examined sera samples from 590 persons, including 418 patients with malignant tumors, 109 patients with benign diseases and 63 healthy persons. We also observed the kinetics of the concentration of nucleosomes in serum samples from 20 patients undergoing chemotherapy and from 16 patients undergoing radiotherapy. Sera of patients with malignant tumors contained considerably higher concentrations of nucleosomes (mean = 350 arbitrary units [AU], median = 190 AU) compared with those of healthy persons (mean = 36 AU, median = 24 AU; p = 0.0001) and patients with benign diseases (mean = 264 AU, median = 146 AU; p = 0.072). Concerning the follow-up investigations, the concentration of nucleosomes in serum increased 24-72 hr after the first application of chemotherapy and 6-24 hr after the start of radiotherapy. A subsequent decrease was often correlated with regression of the tumor. In patients undergoing chemotherapy, an increase in the baseline values of circulating nucleosomes >50%, which were determined before each new therapeutic cycle, was correlated with progression of disease; all patients with disease regression showed a decrease >50% of the baseline values. In patients undergoing radiotherapy, an early decrease of the nucleosomal concentration (< or = 1 day after the initial peak during therapy) to low minimum levels (< or = 100 AU) correlated with good clinical outcome; a late decrease (>1 day) to higher minimum levels (>100 AU) was associated with a worse clinical outcome. Thus, the concentration of nucleosomes in serum might be a useful tool for monitoring the biochemical response during antitumor therapy, especially for the early estimation of therapeutic efficacy.

Cell Death↗
PubMed2001

Alterations of apolipoprotein B metabolism in HIV-infected patients with antiretroviral combination therapy.

BACKGROUND: Dyslipidemia (predominantly hypertriglyceridemia) is frequently seen in patients receiving antiretroviral combination therapy (ART). However, the underlying mechanisms and long-term risks (e.g., cardiovascular events) are still unclear. OBJECTIVES/METHODS: In 5 patients with ART-associated dyslipidemia, stable isotope labeled amino acid tracer (d3-Leu) kinetic analysis over 12 days was used to investigate the metabolism of apolipoprotein B-containing lipoproteins (very low density lipoproteins [VLDL]1, VLDL2, intermediate density lipoproteins [IDL] and low density lipoproteins [LDL]). Data were compared with those in 6 healthy normolipidemic controls. RESULTS: The patients under ART showed significantly increased fasting triglycerides (359 vs. 77 mg/dl) and VLDL (54 vs. 15 mg/dl), compared with controls. They had significantly higher total cholesterol (213 vs. 157 mg/dl) and there was a nonsignificant trend toward higher LDL (136 vs. 93 mg/dl), and toward lower HDL (26 vs. 46 mg/dl). The ratio of large, buoyant LDL1 over small, dense LDL2 was markedly reduced in patients under ART (0.80 vs. 2.00). Total apo B synthesis was significantly increased (25.5 vs. 14.5 mg/kg/d) and shifted toward triglyceride rich VLDL1 (18.5 vs. 8.7 mg/kg/d) in patients receiving ART. There was also a significantly reduced rate of apo B lipoprotein transfer from VLDL1 to VLDL2 (3.7 vs. 20.7 pools/d). In addition, all patients revealed insulin resistance. CONCLUSIONS: These data indicate that increased triglycerides in HIV-infected patients with ART are primary due to reduced rates of VLDL transfer into denser lipoproteins implying a lower rate of lipoprotein lipase-mediated delipidation. In addition, total apo B synthesis was increased and shifted toward triglyceride-rich VLDL1. Overall, this lipoprotein profile in patients with ART-associated dyslipidemia implies an increased risk for cardiovascular events.

Adult↗