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Biomedical subjects

I Friedrich

Publications and source records attributed to I Friedrich.

At least 19 recordsLinked to original sources
PubMed2003

Different expression of cytokines in survivors and non-survivors from MODS following cardiovascular surgery.

OBJECTIVE: Cardiopulmonary bypass is often associated with pathophysiological changes in form of systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS). In the present study, we investigated plasma levels of pro- and anti-inflammatory cytokines in survivors and non-survivors from MODS in the early postoperative course following open heart surgery. DESIGN: Prospective clinical study. SETTING: A University Cardiothoracic Intensive Care Unit. METHODS: Levels of cytokines (IL-6, IL-8, IL-10, IL-18, and TGF- ) and procalcitonin (PCT) were measured at the first four postoperative days in 16 adult male patients with an Apache II-score >24 and two or more organ dysfunctions after myocardial revascularization. MAIN RESULTS: All pro-inflammatory cytokines, except for IL-6, were significantly elevated in non-survivors from MODS, with peak values at the first two postoperative days. The plasma levels of immunoinhibitory cytokines showed no differences between the groups. CONCLUSIONS: The results of our study show a different expression of pro-inflammatory cytokines in survivors and non-survivors from MODS following operations with extracorporeal circulation. In addition to Apache-II score, especially IL-8, IL-18, and PCT may be used as parameters for the prognosis of patients with organ dysfunctions after cardiac surgery.

APACHE↗
PubMed2003

Characterization of solidified reverse micellar solutions (SRMS) and production development of SRMS-based nanosuspensions.

Solidified reverse micellar solutions (SRMS), i.e. binary mixtures of 30-60% (w/w) lecithin and two different hard fats, were investigated regarding their physicochemical properties and the influence of lecithin on solid lipids. For this purpose, the systems were characterized with X-ray and thermal analysis, transmission electron microscopy (TEM) and photon correlation spectroscopy. The melting point (m.p.) of the solid lipids, which is a crucial parameter of the solid state, was not altered up to a lecithin concentration of 50% whereas reverse micelles were likely to be frozen still in the solid state. In addition, solubilities of 17beta-oestradiol-hemihydrate, pilocarpine base and hydrochloride in the SRMS melt were studied for evaluation of the drug carrier potency. Drug solubilization in the SRMS melt increased linearly with rising amount of lecithin. SRMS-based nanosuspensions were developed with a given lecithin/hard fat ratio of 1:1 (w/w). High-pressure homogenization was applied on cold to avoid lecithin loss. Optimization of the systems in terms of a variation of the homogenizing parameters such as pressure, number of cycles and temperature resulted in nanoparticulate systems with a polysorbate 80/SRMS ratio of 1:5 (w/w), and a total amount of 5 and 15% (w/w) SRMS, respectively. Production temperatures near the lipid m.p. proved best to be maintained by varying the pressure, yielding small nanoparticles with a narrow particle size distribution. The solid lipid nanoparticles were characterized with X-ray and thermal analysis as well as TEM. The crystalline particles (beta modification) are of anisometrical shape and have transition temperatures far below the bulk m.p. due to the colloidal character of the systems.

Calorimetry, Differential Scanning↗
PubMed2002

Tumor necrosis factor-alpha production in whole blood after cardiopulmonary bypass: downregulation caused by circulating cytokine-inhibitory activities.

OBJECTIVES: Cardiopulmonary bypass is associated with the release of proinflammatory cytokines (tumor necrosis factor alpha, interleukin 1beta, interleukin 6, and interleukin 8) and anti-inflammatory cytokines (interleukin 10 and transforming growth factor beta(1)). On the one hand this cytokine release is related to the postoperative systemic inflammatory response syndrome, and on the other hand it is related to deterioration of the immune system, for example in monocyte or polymorphonuclear neutrophil function, leading to an increased susceptibility to infections. To gain further insight into the alterations of immune cell reactivity and possible regulatory mechanisms, we studied lipopolysaccharide-induced tumor necrosis factor alpha synthesis in whole blood from cardiac surgical patients. METHODS: Fifteen patients undergoing elective heart surgery with cardiopulmonary bypass were included in the study. Ex vivo lipopolysaccharide-induced tumor necrosis factor alpha synthesis was measured in a whole blood assay before, during, and after bypass. Corresponding tumor necrosis factor alpha messenger RNA levels were determined by semiquantitative reverse transcriptase-polymerase chain reaction. In addition, the influence of patient serum on whole blood responsiveness and its relationship to anti-inflammatory cytokines were evaluated in vitro. RESULTS: Tumor necrosis factor alpha synthesis was significantly reduced after 30 minutes of cardiopulmonary bypass and showed the lowest values at the end of bypass (mean +/- SD 0.109 +/- 0.105 ng/10(6) white blood cells after 30 minutes of bypass and 0.050 +/- 0.065 ng/10(6) white blood cells at the end of bypass, vs 0.450 +/- 0.159 ng/10(6) white blood cells preoperatively, P <.001). As a further indication of reduced cytokine biosynthesis, diminished messenger RNA levels for tumor necrosis factor alpha were detected. Serum withdrawn from patients at the end of cardiopulmonary bypass reduced tumor necrosis factor alpha synthesis in heterologous blood from healthy volunteers highly significantly to 39.93% +/- 23.18% relative to control serum (P =.005) and preoperatively drawn serum (P =.024). This effect was dose dependent and was not specific for lipopolysaccharide-induced tumor necrosis factor alpha synthesis. Anesthesia and heparin administration did not influence tumor necrosis factor alpha production significantly. Ex vivo tumor necrosis factor alpha synthesis was negatively related to interleukin 10 serum levels, positively but weakly related to interleukin 4, and was not related to transforming growth factor beta(1) (Spearman correlation coefficients -0.565, P <.001, 0.362, P <.001, and -0.062, P =.460, respectively). However, interleukin 10 levels in patient serum after cardiopulmonary bypass were 300-fold below the quantities needed for half-maximal inhibition of tumor necrosis factor alpha synthesis in vitro. Moreover, the inhibitory activity could not be removed by immune absorption of interleukin 10. CONCLUSIONS: These results suggest that during cardiac operations cytokine-inhibitory serum activities are released or newly formed. These activities could not be explained by the actions of interleukins 4 and 10 or transforming growth factor beta(1). Although their exact nature remains undetermined, these substances may contribute to the diminished immune cell functions after cardiopulmonary bypass and thus need further characterization.

Aged↗
PubMed2001

Ischemic pre-conditioning of 5 minutes but not of 10 minutes improves lung function after warm ischemia in a canine model.

BACKGROUND: Protection from reperfusion injury by ischemic pre-conditioning (IPC) before prolonged ischemia has been proven for the heart and the liver. We now assess the efficacy of IPC to protect lungs from reperfusion injury. METHODS: Eighteen foxhounds (25 to 30 kg) were anesthetized, intubated, and ventilated with a fraction of inspired oxygen of 0.3 at a volume-controlled mode to maintain arterial pCO2 of 30 to 40 mm Hg. After left thoracotomy, we performed warm ischemia for 3 hours by clamping the left hilus, and followed with 8 hours of reperfusion (control, n = 6). In the treated groups, IPC was performed either for 5 minutes followed by 15-minute reperfusion (n = 6, IPC-5), or by 2 successive cycles of 10-minute ischemia, followed by 10-minute reperfusion (n = 6, IPC-10) before prior to the 3-hours warm-ischemia period. Pulmonary compliance and gas exchange were determined separately for each lung, and we recorded pulmonary and systemic hemodynamics. We performed bronchoalveolar lavage (BAL) at the end of the experiment and determined total protein concentration as well as tumor necrosis factor alpha (TNF-alpha) mRNA expression in cell-free supernatant and in BAL cells, respectively. We also assessed the wet/dry ratio of the lung. RESULTS: In the controls, on reperfusion, we encountered a progressive deterioration of gas exchange, especially of the reperfused left lung, which we could largely avoid using the IPC-5 protocol. Similarly, pulmonary compliance steadily declined but was much better in the ICP-5 group. Parallel to the improvement of gas exchange and lung mechanics, we found less total alveolar protein content and TNF-alpha mRNA expression in BAL cells in the IPC-5 than in the controls. However, we did not find IPC-10 to be paralleled by a significant improvement of lung function. Neither IPC-5 nor IPC-10 influenced the pulmonary vascular resistance index or the fluid accumulation in the lung. CONCLUSION: The major finding of the present study was that 5 minutes of IPC improved lung function after 3 hours of warm ischemia of the lung.

Animals↗
PubMed2001

Lipopolysaccharide-binding protein (LBP) and markers of acute-phase response in patients with multiple organ dysfunction syndrome (MODS) following open heart surgery.

Cardiopulmonary bypass (CPB) is associated with an immunological injury that may cause pathophysiological alterations in the form of a systemic inflammatory response syndrome (SIRS) or a multiple organ dysfunction syndrome (MODS). Previous studies on this issue have reported different changes of immunological parameters during and after CPB, but there are no reports about the lipopolysaccharide-binding protein (LBP) in relationship to other markers of inflammation in patients with MODS following cardiovascular surgery. In the present study, we investigated the acute-phase response of patients with MODS of infectious and non-infectious origin following open-heart-surgery. Plasma levels of procalcitonin (PCT), c-reactive protein (CRP), interleukin-6 (IL-6), and LBP were measured in the first four postoperative days in 12 adult male patients with the signs of SIRS and two or more organ dysfunctions after myocardial revascularization (MODS-group), and 12 patients without organ insufficiencies (SIRS-group). There were no significant differences regarding age, weight, height, preoperative NYHA-classification, preoperative LVEDP, or the number of anastomosis. Patients with MODS had a significantly longer operation time, duration of ischemia, and duration of extracorporeal circulation. None of the patients in the SIRS group died, whereas in the MODS group, 4 patients died due to septic multiorgan failure. Plasma PCT and IL-6 concentrations were significantly elevated in all MODS patients. CRP and LBP showed no differences between the MODS and the SIRS group. Comparing the MODS patients with and without positive microbial findings, we found significantly elevated levels of PCT and LBP in those patients with documented infections. Our results indicate that LBP may be a new marker for the differentiation between a severe non-infectious SIRS and an ongoing bacterial sepsis in the early postoperative course following CPB, while a microbiological result is still missing.

APACHE↗
PubMed2001

Treatment of sepsis in cardiac surgery: role of immunoglobulins.

Cardiopulmonary bypass (CPB) is associated with an injury that may cause pathophysiological changes such as systemic inflammatory response syndrome, multiple organ dysfunction syndrome, and mediator-induced multiorgan failure. Systemic endotoxinaemia, release of proinflammatory cytokines, and interactions between neutrophils and endothelium have been reported to correlate with a high incidence of organ dysfunction, infection and sepsis following cardiac surgery. This review discusses the dysregulation of the immune response as a major reason for the higher susceptibility to infections following cardiac surgery, various treatment strategies to reduce CPB-induced inflammation, and especially the prophylactic use of immunoglobulins in cardiac surgery.

Cardiopulmonary Bypass↗
PubMed2000

[Diabetic ketoacidosis during the Ramadan fast].

We report a 15-year-old Muslim boy with insulin-dependent diabetes mellitus (IDDM) who presented with diabetic ketoacidosis (DKA) during the Muslim Ramadan month of day-time fasting. DKA apparently occurred due to omitting pre-lunch insulin combined with dehydration and overeating during the permitted sunset-to-sunrise meals. It is well-known that fasting accelerates development of lipolysis and ketosis and increases glucagon levels. Thus, these pathophysiological aberrations related to fasting in ketosis-prone patients, in conjunction with fasting, endanger metabolic control in IDDM.

Adolescent↗
PubMed2000

Heterogeneity of cardiac rat and human elongation factor 2.

Elongation factor 2 (EF-2) catalyses the last step of the elongation cycle, translocation, in the course of protein biosynthesis. A system for analyzing post-translational modifications of EF-2, which is a single polypeptide of 857 amino acids, is reported and its application to cytosolic extracts of cultured neonatal rat heart myocytes, neonatal and adult rat cardiac tissue, and extracts of human left ventricular myocardium is described. Comparing different pH ranges in immobilized pH gradient-isoelectric focusing (IPG-IEF), a range of pH 3 - 10 and 4 - 9 resulted in a highly defined and reproducible resolution of six different EF-2 variants of all extracts in the first dimension. These six variants were detected by the "imaging plate" (phosphor radiation image sensor) after specific labeling with Pseudomonas exotoxin A catalyzed [32P]ADP-ribosylation. This finding could be confirmed in Western blot analysis with a specific polyclonal rabbit antibody. Using two-dimensional polyacrylamide gel electrophoresis (2-D-PAGE), five to six EF-2 variants could be demonstrated in all extracts. By application of a second IPG indicator strip to the 2-D gel, they could be aligned with corresponding spots in a silver-stained 2-D separation of human myocardial tissue, revealing that the EF-2 variants belong to the group of low-abundance proteins.

Adenosine Diphosphate Ribose↗
PubMed2000

HDL steady state levels are not affected, but HDL apoA-I turnover is enhanced by Lifibrol in patients with hypercholesterolemia and mixed hyperlipidemia.

Lifibrol (4-(4'-tert-butylphenyl)-1-(4'carboxyphenoxy)-2-butanol) is a new hypocholesterolemic drug effectively reducing total cholesterol, LDL cholesterol, and apolipoprotein (apo) B in experimental animals and in humans. In contrast to fibrates and HMG-CoA reductase inhibitors the cholesterol and triglyceride lowering effect of Lifibrol is not accompanied by increases in HDL cholesterol and apoA-I levels. We examined the impact of Lifibrol on the metabolism of HDL apoA-I in patients with hyperlipoproteinemia, using endogenous labeling with stable isotopes. Kinetic studies were performed in five male hypercholesterolemic individuals (type IIa), before and on treatment with 450 mg of Lifibrol daily for 4 weeks and in five male individuals suffering from mixed hyperlipidemia (type IIb), before and on therapy, for 12 weeks. Lifibrol reduced total cholesterol by 14% (P=0.02) and LDL cholesterol by 16% (P=0. 014) in all patients, and decreased triglycerides by 34% in type IIb patients. During Lifibrol therapy, HDL cholesterol and ApoA-I concentrations did not change. Tracer kinetics revealed that the fractional catabolic rate (FCR) of HDL apoA-I increased by 22% (P=0. 013). This increase in the apoA-I FCR was accompanied by a 23% increase in HDL apoA-I production rate (P=0.006). We conclude that Lifibrol, although not changing HDL steady state concentrations, enhances the turnover of apoA-I containing HDL particles.

Adult↗
PubMed2000

Low density lipoprotein (LDL) subfractions during pregnancy: accumulation of buoyant LDL with advancing gestation.

Pregnancy is accompanied by changes in the maternal lipoprotein metabolism that may serve to satisfy the nutritional demands of the fetus. In this study lipoprotein metabolism was investigated in 23 women during normal pregnancy in the first, second, and third trimesters and in 15 healthy nonpregnant women with regular menstrual cycles. Lipid and apolipoprotein concentrations were measured in total plasma, very low density, intermediate density, low density (LDL), and high density lipoproteins, and in each of six LDL subfractions. During early pregnancy, triglycerides, and dense LDL were higher than in the nonpregnant state. With advancing gestation, triglycerides increased and the distribution of apolipoprotein B-100-containing lipoproteins became increasingly dominated by the accumulation of very low density and intermediate density lipoproteins and buoyant, triglyceride-rich LDL. This is the first study that investigates LDL subfractions in pregnancy using a method that strictly separates LDL subfractions by virtue of density. The accumulation of buoyant, triglyceride-rich lipoproteins may be related to the down-regulation of maternal lipase activities by placental hormones. As a consequence, the metabolic changes of late pregnancy may result in an increased flux of lipoprotein-derived lipids to the placenta, which, with advancing gestation, increasingly expresses receptors with a high affinity for triglyceride-rich lipoproteins.

Adult↗
PubMed2000

Physicochemical characterization of a reverse micellar solution after loading with different drugs.

Diclofenac sodium (DS), timolol maleate (TM) and pilocarpine hydrochloride (PHCl) were solubilized in a reverse micellar solution (RMS) consisting of lecithin and middle-chain triglycerides (MCT). The influence of these drugs on the physicochemical parameters of the RMS was investigated. Although none of the drugs influenced the size of the associates, the micellar shapes varied considerably. While DS and PHCl increased the anisometry, reverse micelles with TM were spherical. The transformation of the RMS into a lamellar mesophase on contact with water was generally not prevented by any of the drugs but all drugs led to an increased number of defect structures in the liquid crystal. Furthermore the interlayer distance of the lamellar mesophase was reduced by a higher content of DS. In comparison with an RMS containing isopropylmyristate (IPM) instead of MCT, differences in the physicochemical properties of the drug-free RMS and in the influences of solubilized drugs were noticed.

Chemical Phenomena↗
PubMed1999

Lifibrol enhances the low density lipoprotein apolipoprotein B-100 turnover in patients with hypercholesterolemia and mixed hyperlipidemia.

Lifibrol (4-(4'-tert-butylphenyl)-1-(4'carboxyphenoxy)-2-butanol), a new hypocholesterolemic drug, effectively reduces total cholesterol (CH), low density lipoprotein (LDL)-CH, and apolipoprotein (apo) B in experimental animals and in humans. The impact of Lifibrol on the metabolism of apoB-100 containing lipoproteins in patients with hyperlipoproteinemia using endogenous labeling with stable isotopes is examined. Kinetic studies were performed in four male hypercholesterolemic individuals (type IIa) before and on treatment with 450 mg of Lifibrol daily for 4 weeks, and in five male individuals suffering from mixed hyperlipidemia (type IIb) before and on therapy for 12 weeks. Kinetic parameters were estimated by multicompartmental modeling. Lifibrol therapy reduced total CH by 16% (P = 0.012) in all patients, increased triglycerides (TG) by 11% (not significant) in type IIa patients and decreased TG by 34% (P = 0.059) in type IIb patients. During Lifibrol therapy, LDL apoB-100 concentrations decreased by 19% (P = 0.011) in all patients. The decrease in LDL apoB concentrations with Lifibrol therapy was due to an overall increase (75%, P = 0.006) of the fractional catabolic rates (FCR) of LDL apoB. This increase was partially attenuated by a 33% increase in LDL apoB production rate (PR) (P = 0.041). The overall production of apoB increased only slightly. Our data suggest that the major mechanism by which Lifibrol lowers LDL-CH is an increase in receptor-mediated catabolism of LDL rather than a decrease in hepatic apoB production.

Adult↗
PubMed1999

Altered lipid metabolism in preeclampsia and HELLP syndrome: links to enhanced platelet reactivity and fetal growth.

Normal pregnancy is a physiological condition of balanced hypercoagulability. However, in preeclamptic pregnancies, the coagulation and fibrinolytic cascades are highly activated, accompanied by pathological blood rheology and endothelial dysfunction. This may result in disseminated intravascular coagulation (DIC). Atherosclerosis research showed that lipids may interfere with coagulation and cause endothelial dysfunction. Therefore, we analyzed the lipoprotein distribution and platelet counts in uncomplicated preeclamptic and HELLP syndrome pregnancies. In addition, a correlation between the fetal circulation determined by Doppler velocimetry and the maternal lipid metabolism was investigated. Fasting serum was collected from 24 women in the third trimester of uncomplicated pregnancies, 9 women with severe preeclampsia, and 6 women with HELLP syndrome. Cholesterol (CH), triglycerides (TGs), and apolipoproteins were analyzed in serum and in very-low-density (VLDL), intermediate-density (IDL), low-density (LDL), and high-density (HDL) lipoproteins separated by ultra-centrifugation. Compared with normal pregnancies, TGs in serum, VLDL, IDL, LDL, and HDL were significantly increased in preeclampsia; no difference in CH concentrations was observed. During HELLP syndrome, IDL-TGs were increased compared with normal pregnancies. There was no clear correlation between fetal hemodynamics and maternal lipid metabolism, but there was a significant negative correlation between maternal platelet counts and serum TG levels. Because TG-rich particles may play an important role in thrombin generation and may induce platelet aggregation, the observed changes in lipoprotein metabolism in preeclampsia and HELLP syndrome may contribute to the coagulopathy seen in these conditions.

Adult↗
PubMed1999

Competition of Abeta amyloid peptide and apolipoprotein E for receptor-mediated endocytosis.

The genetic polymorphism of apolipoprotein E (apoE) is associated with the age of onset and relative risk of Alzheimer's disease (AD). In contrast to apoE3, the wild type allele, apoE4 confers an increased risk of late-onset AD. We demonstrate that the beta-amyloid peptide isoforms Abeta (1-28), Abeta (1-40), and Abeta (1-43) compete for the cellular metabolism of apoE3 and apoE4 containing beta-very low density lipoproteins. An antibody raised against Abeta (1-28) cross-reacted with recombinant apoE. Epitope mapping revealed positive amino acid clusters as common epitopes of Abeta (13 through 17; HHQKL) and apoE (residues 144 through 148; LRKRL), both regions known to be heparin binding domains. Abeta in which amino acids 13 through 17 (HHQKL) were replaced by glycine (GGQGL) failed to compete with the cellular uptake of apoE enriched betaVLDL. These observations indicate that Abeta and apoE are taken up into cells by a common pathway involving heparan sulfate proteoglycans.

Alzheimer Disease↗
PubMed1999

Treatment of carotid artery stenosis by elective stent placement instead of carotid endarterectomy in patients with severe coronary artery disease.

Patients with concomitant cardiac and cerebrovascular disease undergoing revascularization procedures are at high risk of both, cardiac and cerebrovascular complications. The purpose of our study was to evaluate the feasibility of prior elective carotid artery stenting as an alternative treatment procedure to carotid endarterectomy (CEA) in patients with concomitant coronary artery disease (CAD), who clearly needed coronary revascularization. We offered extracranial internal carotid stenting to 85 patients with 89 significant carotid stenoses. Out of these, 19 patients were symptomatic. The quantitative mean reduction in diameter was 77 +/- 11%. Stent implantation was successful in 88 lesions. Two disabling major and 3 reversible minor strokes occurred periprocedurally. Three patients showed asymptomatic restenosis and stent deformation was detected in 2 patients. Based on this experience, carotid stenting in high risk patients with severe coronary artery disease is feasible and safe and might be indicated as an alternative procedure for combined surgery.

Adult↗
PubMed1996

Clearance of postprandial lipoproteins in normolipemics: role of the apolipoprotein E phenotype.

The hepatic clearance of triglyceride-rich lipoproteins is mediated via apolipoprotein (apo) E which occurs in three common isoforms, apoE2, apoE3 and apoE4. To study the importance of the apoE isoforms on the response curves of different triglyceride-rich lipoproteins and the effect of chylomicron remnants on the composition of HDL, 37 normolipemics were investigated after a standardized fatty meal (8 apoE2/E2, 8 apoE2/E3, 8 apoE3/E3, 7 apoE3/E4 and 6 apoE4/E4). These individuals were matched for age, body mass index, fasting triglycerides, HDL-cholesterol, and apoA-I. A delayed chylomicron remnant clearance was observed only in apoE2 homozygotes, and this delay was neither correlated with fasting lip ds nor with peak lipoprotein concentrations. In apoE2/E3 heterozygotes, in contrast, the defective isoform E2 appears to be compensated for by the normal apoE isoform E3. In non-apo-E2/E2 individuals, the chylomicron remnant response was highly correlated with the magnitude of chylomicron and VLDL responses, with fasting triglycerides, and with the triglycerides enrichment and cholesterol depletion of HDL. These correlations were not observed in apoE2/E2. From these results we conclude that the chylomicron remnant response curve is an indicator of the extent of postprandial lipemia in non-apoE2/E2 individuals only.

Adult↗
PubMed1996

Exposing the circumflex coronary artery: the heartflip technique.

A method to expose the circumflex coronary artery in its course in the atrioventricular groove is introduced. No special equipment or assistance is required. This method also can be applied to expose the obtuse marginal branches of the circumflex coronary artery. Adverse effects have not been observed.

Cardiac Surgical Procedures↗