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Background: Chronic kidney disease (CKD) is a frequent comorbidity among elderly patients and those with cardiovascular disease. CKD carries prognostic relevance. We aimed to describe patient characteristics, risk factor management and control status of patients in cardiac rehabilitation (CR), differentiated by presence or absence of CKD.
Design and methods: Data from 92,071 inpatients with adequate information to calculate glomerular filtration rate (GFR) based on the Cockcroft-Gault formula were analyzed at the beginning and the end of a 3-week CR stay. CKD was defined as estimated GFR <60 ml/min/1.73 m(2).
Results: Compared with non-CKD patients, CKD patients were significantly older (72.0 versus 58.0 years) and more often had diabetes mellitus, arterial hypertension, and atherothrombotic manifestations (previous stroke, peripheral arterial disease), but fewer were current or previous smokers had a CHD family history. Exercise capacity was much lower in CKD (59 vs. 92Watts). Fewer patients with CKD were treated with percutaneous coronary intervention (PCI), but more had coronary artery bypass graft (CABG) surgery. Patients with CKD compared with non-CKD less frequently received statins, acetylsalicylic acid (ASA), clopidogrel, beta blockers, and angiotensin converting enzyme (ACE) inhibitors, and more frequently received angiotensin receptor blockers, insulin and oral anticoagulants. In CKD, mean low density lipoprotein cholesterol (LDL-C), total cholesterol, and high density lipoprotein cholesterol (HDL-C) were slightly higher at baseline, while triglycerides were substantially lower. This lipid pattern did not change at the discharge visit, but overall control rates for all described parameters (with the exception of HDL-C) were improved substantially. At discharge, systolic blood pressure (BP) was higher in CKD (124 versus 121 mmHg) and diastolic BP was lower (72 versus 74 mmHg). At discharge, 68.7% of CKD versus 71.9% of non-CKD patients had LDL-C <100 mg/dl. Physical fitness on exercise testing improved substantially in both groups. When the Modification of Diet in Renal Disease (MDRD) formula was used for CKD classification, there was no clinically relevant change in these results.
Conclusion: Within a short period of 3-4 weeks, CR led to substantial improvements in key risk factors such as lipid profile, blood pressure, and physical fitness for all patients, even if CKD was present.
Background: Chronic kidney disease (CKD) is a frequent comorbidity among elderly patients and those with cardiovascular disease. CKD carries prognostic relevance. We aimed to describe patient characteristics, risk factor management and control status of patients in cardiac rehabilitation (CR), differentiated by presence or absence of CKD.
Design and methods: Data from 92,071 inpatients with adequate information to calculate glomerular filtration rate (GFR) based on the Cockcroft-Gault formula were analyzed at the beginning and the end of a 3-week CR stay. CKD was defined as estimated GFR <60 ml/min/1.73 m(2).
Results: Compared with non-CKD patients, CKD patients were significantly older (72.0 versus 58.0 years) and more often had diabetes mellitus, arterial hypertension, and atherothrombotic manifestations (previous stroke, peripheral arterial disease), but fewer were current or previous smokers had a CHD family history. Exercise capacity was much lower in CKD (59 vs. 92Watts). Fewer patients with CKD were treated with percutaneous coronary intervention (PCI), but more had coronary artery bypass graft (CABG) surgery. Patients with CKD compared with non-CKD less frequently received statins, acetylsalicylic acid (ASA), clopidogrel, beta blockers, and angiotensin converting enzyme (ACE) inhibitors, and more frequently received angiotensin receptor blockers, insulin and oral anticoagulants. In CKD, mean low density lipoprotein cholesterol (LDL-C), total cholesterol, and high density lipoprotein cholesterol (HDL-C) were slightly higher at baseline, while triglycerides were substantially lower. This lipid pattern did not change at the discharge visit, but overall control rates for all described parameters (with the exception of HDL-C) were improved substantially. At discharge, systolic blood pressure (BP) was higher in CKD (124 versus 121 mmHg) and diastolic BP was lower (72 versus 74 mmHg). At discharge, 68.7% of CKD versus 71.9% of non-CKD patients had LDL-C <100 mg/dl. Physical fitness on exercise testing improved substantially in both groups. When the Modification of Diet in Renal Disease (MDRD) formula was used for CKD classification, there was no clinically relevant change in these results.
Conclusion: Within a short period of 3-4 weeks, CR led to substantial improvements in key risk factors such as lipid profile, blood pressure, and physical fitness for all patients, even if CKD was present.
We tested, in the laboratory, the influence of light intensity, temperature, and phosphorus (P) supply on fatty acid (FA) concentrations of four freshwater algae: the green algae Scenedesmus quadricauda (Turpin) Breb. and Chlamydomonas globosa J. Snow, the cryptophyte Cryptomonas ovata Ehrenb., and the diatom Cyclotella meneghiniana Kutz. We investigated the main and interactive effects of two variables on algal FA concentrations (i.e., light intensity and P supply or temperature and P supply). Interactive effects of light intensity and P supply were most pronounced in C. meneghiniana, but were also found in S. quadricauda and C. ovata. Changes in several saturated and unsaturated FA concentrations with light were more distinct in the low-P treatments than in the high-P treatments. Interactive effects of temperature and P supply on various FA concentrations were observed in all four species, but there was no consistent pattern. In lake ecosystems, P limitation often coincides with high light intensities and temperatures in summer. Therefore, it is important to examine how combinations of these environmental conditions affect FA concentrations of primary producers that are important sources of FAs for higher trophic levels.
Studies have revealed mixed results on how antidepressant drugs affect lipid profiles of patients with major depression disorder (MDD). Even less is known about how patients respond to a switch of antidepressant medication with respect to their metabolic profile. For this, effects of a switch in antidepressants medication on lipid markers were studied in MDD patients. 15 participants (females = 86.67%; males = 13.33%; age: 49.45 ± 7.45 years) with MDD and a prescribed switch in their antidepressant medication were recruited at a psychosomatic rehabilitation clinic. Participants were characterized (with questionnaires and blood samples) at admission to the rehabilitation clinic (baseline, T0) and followed up with a blood sample two weeks (T1) later. HDL, LDL, total cholesterol, and triglycerides were determined (T0), and their change analyzed (Wilcoxon test) at follow up (T1). Decrements in HDL (p = 0.041), LDL (p < 0.001), and total cholesterol (p < 0.001) were observed two weeks after a switch in antidepressant medication. Triglycerides showed no difference (p = 0.699). Overall, LDL, HDL, and total cholesterol are affected by a change in antidepressant drugs in patients with MDD. These observations are of clinical relevance for medical practitioners in the planning and management of treatment strategies for MDD patients.
Studies have revealed mixed results on how antidepressant drugs affect lipid profiles of patients with major depression disorder (MDD). Even less is known about how patients respond to a switch of antidepressant medication with respect to their metabolic profile. For this, effects of a switch in antidepressants medication on lipid markers were studied in MDD patients. 15 participants (females = 86.67%; males = 13.33%; age: 49.45 ± 7.45 years) with MDD and a prescribed switch in their antidepressant medication were recruited at a psychosomatic rehabilitation clinic. Participants were characterized (with questionnaires and blood samples) at admission to the rehabilitation clinic (baseline, T0) and followed up with a blood sample two weeks (T1) later. HDL, LDL, total cholesterol, and triglycerides were determined (T0), and their change analyzed (Wilcoxon test) at follow up (T1). Decrements in HDL (p = 0.041), LDL (p < 0.001), and total cholesterol (p < 0.001) were observed two weeks after a switch in antidepressant medication. Triglycerides showed no difference (p = 0.699). Overall, LDL, HDL, and total cholesterol are affected by a change in antidepressant drugs in patients with MDD. These observations are of clinical relevance for medical practitioners in the planning and management of treatment strategies for MDD patients.
Interactions involving biological interfaces such as lipid-based membranes are of paramount importance for all life processes. The same also applies to artificial interfaces to which biological matter is exposed, for example the surfaces of drug delivery systems or implants. This thesis deals with the two main types of interface interactions, namely (i) interactions between a single interface and the molecular components of the surrounding aqueous medium and (ii) interactions between two interfaces. Each type is investigated with regard to an important scientific problem in the fields of biotechnology and biology:
1.) The adsorption of proteins to surfaces functionalized with hydrophilic polymer brushes; a process of great biomedical relevance in context with harmful foreign-body-response to implants and drug delivery systems.
2.) The influence of glycolipids on the interaction between lipid membranes; a hitherto largely unexplored phenomenon with potentially great biological relevance.
Both problems are addressed with the help of (quasi-)planar, lipid-based model surfaces in combination with x-ray and neutron scattering techniques which yield detailed structural insights into the interaction processes. Regarding the adsorption of proteins to brush-functionalized surfaces, the first scenario considered is the exposure of the surfaces to human blood serum containing a multitude of protein species. Significant blood protein adsorption was observed despite the functionalization, which is commonly believed to act as a protein repellent. The adsorption consists of two distinct modes, namely strong adsorption to the brush grafting surface and weak adsorption to the brush itself. The second aspect investigated was the fate of the brush-functionalized surfaces when exposed to aqueous media containing immune proteins (antibodies) against the brush polymer, an emerging problem in current biomedical applications. To this end, it was found that antibody binding cannot be prevented by variation of the brush grafting density or the polymer length. This result motivates the search for alternative, strictly non-antigenic brush chemistries. With respect to the influence of glycolipids on the interaction between lipid membranes, this thesis focused on the glycolipids’ ability to crosslink and thereby to tightly attract adjacent membranes. This adherence is due to preferential saccharide-saccharide interactions occurring among the glycolipid headgroups. This phenomenon had previously been described for lipids with special oligo-saccharide motifs. Here, it was investigated how common this phenomenon is among glycolipids with a variety of more abundant saccharide-headgroups. It was found that glycolipid-induced membrane crosslinking is equally observed for some of these abundant glycolipid types, strongly suggesting that this under-explored phenomenon is potentially of great biological relevance.
A detailed description of the characteristics of antimicrobial peptides (AMPs) is highly demanded, since the resistance against traditional antibiotics is an emerging problem in medicine. They are part of the innate immune system in every organism, and they are very efficient in the protection against bacteria, viruses, fungi and even cancer cells. Their advantage is that their target is the cell membrane, in contrast to antibiotics which disturb the metabolism of the respective cell type. This allows AMPs to be more active and faster. The lack of an efficient therapy for some cancer types and the evolvement of resistance against existing antitumor agents make AMPs promising in cancer therapy besides being an alternative to traditional antibiotics. The aim of this work was the physical-chemical characterization of two fragments of LL-37, a human antimicrobial peptide from the cathelicidin family. The fragments LL-32 and LL-20 exhibited contrary behavior in biological experiments concerning their activity against bacterial cells, human cells and human cancer cells. LL-32 had even a higher activity than LL-37, while LL-20 had almost no effect. The interaction of the two fragments with model membranes was systematically studied in this work to understand their mode of action. Planar lipid films were mainly applied as model systems in combination with IR-spectroscopy and X-ray scattering methods. Circular Dichroism spectroscopy in bulk systems completed the results. In the first approach, the structure of the peptides was determined in aqueous solution and compared to the structure of the peptides at the air/water interface. In bulk, both peptides are in an unstructured conformation. Adsorbed and confined to at the air-water interface, the peptides differ drastically in their surface activity as well as in the secondary structure. While LL-32 transforms into an α-helix lying flat at the water surface, LL-20 stays partly unstructured. This is in good agreement with the high antimicrobial activity of LL-32. In the second approach, experiments with lipid monolayers as biomimetic models for the cell membrane were performed. It could be shown that the peptides fluidize condensed monolayers of negatively charged DPPG which can be related to the thinning of a bacterial cell membrane. An interaction of the peptides with zwitterionic PCs, as models for mammalian cells, was not clearly observed, even though LL-32 is haemolytic. In the third approach, the lipid monolayers were more adapted to the composition of human erythrocyte membranes by incorporating sphingomyelin (SM) into the PC monolayers. Physical-chemical properties of the lipid films were determined and the influence of the peptides on them was studied. It could be shown that the interaction of the more active LL-32 is strongly increased for heterogeneous lipid films containing both gel and fluid phases, while the interaction of LL-20 with the monolayers was unaffected. The results indicate an interaction of LL-32 with the membrane in a detergent-like way. Additionally, the modelling of the peptide interaction with cancer cells was performed by incorporating some negatively charged lipids into the PC/SM monolayers, but the increased charge had no effect on the interaction of LL-32. It was concluded, that the high anti-cancer activity of the peptide originates from the changed fluidity of cell membrane rather than from the increased surface charge. Furthermore, similarities to the physical-chemical properties of melittin, an AMP from the bee venom, were demonstrated.
Ellipsometrische Lichtstreuung als neue Methode zur Charakterisierung der Grenzfläche von Kolloiden
(2004)
Die ellipsometrische Lichtstreuung wird als eine neue, leistungsfähige Methode zur Charakterisierung von Schichten um kolloidale Partikel vorgestellt. Theoretische Grundlage der Methode ist die Mie-Theorie der Lichtstreuung. Experimentell wurde die Polarisationsoptik eines Null-Ellipsometers in den Strahlengang eines Lichtstreuaufbaus eingebaut. Wie in der Reflexionsellipsometrie um den Brewsterwinkel herum erhält man in der ellipsometrischen Streuung einen Winkelbereich, in dem die Methode empfindlich auf Schichten an der Oberfläche der Partikel ist. An verschiedenen Systemen wurde die Tauglichkeit der ellipsometrischen Streuung zur Charakterisierung von Schichten auf Partikeln demonstriert. So wurden Dicke und Brechungsindex einer thermosensitiven Schicht von Poly(N-isopropylacrylamid) auf einem Poly(methylmethacrylat)-Kern bestimmt. Damit ist es möglich, experimentell den Schichtbrechungsindex und damit den Quellungsgrad zu bestimmen. Des Weiteren wurde der Einfluss der NaCl-Konzentration auf die Polyelektrolythülle von Poly(methylmethacrylat)-Poly(styrolsulfonat)-Blockcopolymer-Partikeln untersucht. Die Polyelektrolytketten liegen im hier untersuchten Beispiel nicht gestreckt vor. Als drittes wurde die Verteilung von niedermolekularen Ionen um elektrostatisch stabilisierte Poly(styrol)-Latexpartikel in Wasser untersucht. Hier wurde gezeigt, dass die beobachteten Schichtdicken und Schichtbrechungsindizes viel größer sind, als nach der klassischen Poisson-Boltzmann-Theorie zu erwarten ist. Des Weiteren wurde die Doppelbrechung von unilamellaren Lipidvesikeln bestimmt. Außerdem wurden Messungen der dynamische Lichtstreuung im Intensitätsminimum der Ellipsometrie durchgeführt. Dabei wird ein Prozess mit einer Korrelationszeit, die unabhängig vom Streuvektor, aber abhängig von der verwendeten Wellenlänge ist, sichtbar. Die Natur dieses Prozesses konnte hier nicht vollständig geklärt werden.
Red, orange or green snow is the macroscopic phenomenon comprising different eukaryotic algae. Little is known about the ecology and nutrient regimes in these algal communities. Therefore, eight snow algal communities from five intensively tinted snow fields in western Spitsbergen were analysed for nutrient concentrations and fatty acid (FA) composition. To evaluate the importance of a shift from green to red forms on the FA-variability of the field samples, four snow algal strains were grown under nitrogen replete and moderate light (+N+ML) or N-limited and high light (-N+HL) conditions. All eight field algal communities were dominated by red and orange cysts. Dissolved nutrient concentration of the snow revealed a broad range of NH4+ (<0.005-1.2 mg NI-1) and only low PO43- (< 18 mu g P I-1) levels. The external nutrient concentration did not reflect cellular nutrient ratios as C:N and C:P ratios of the communities were highest at locations containing relatively high concentrations of NH4- and PO43-. Molar N:P ratios ranged from 11 to 21 and did not suggest clear limitation of a single nutrient. On a per carbon basis, we found a 6-fold difference in total FA content between the eight snow algal communities, ranging from 50 to 300 mg FA g C-1. In multivariate analyses total FA content opposed the cellular N:C quota and a large part of the FA variability among field locations originated from the abundant FAs C181n-9, C18 2n-6, and C183n-3. Both field samples and snow algal strains grown under -N+HL conditions had high concentrations of C181n-9. FAs possibly accumulated due to the cessation of growth. Differences in color and nutritional composition between patches of snow algal communities within one snow field were not directly related to nutrient conditions. We propose that the highly patchy distribution of snow algae within and between snow fields may also result from differences in topographical and geological parameters such as slope, melting water rivulets, and rock formation.
Alkylphospholipids are a novel class of antineoplastic drugs showing remarkable therapeutic potential. Among them, erufosine (EPC3) is a promising drug for the treatment of several types of tumors. While EPC3 is supposed to exert its function by interacting with lipid membranes, the exact molecular mechanisms involved are not known yet. In this work, we applied a combination of several fluorescence microscopy and analytical chemistry approaches (i.e., scanning fluorescence correlation spectroscopy, line-scan fluorescence correlation spectroscopy, generalized polarization imaging, as well as thin layer and gas chromatography) to quantify the effect of EPC3 in biophysical models of the plasma membrane, as well as in cancer cell lines. Our results indicate that EPC3 affects lipid–lipid interactions in cellular membranes by decreasing lipid packing and increasing membrane disorder and fluidity. As a consequence of these alterations in the lateral organization of lipid bilayers, the diffusive dynamics of membrane proteins are also significantly increased. Taken together, these findings suggest that the mechanism of action of EPC3 could be linked to its effects on fundamental biophysical properties of lipid membranes, as well as on lipid metabolism in cancer cells.