Influence of different fat emulsions with 10 or 20% MCT/LCT or LCT on lipoproteins in plasma of patients after abdominal surgery

In patients after elective abdominal surgery, different fat emulsions were used to compare their efficacy in total parenteral nutrition and in normalizing plasma lipoprotein levels. In five different groups with 5 patients each, half of the nonprotein calories were given as medium-chain triglycerides/ long-chain triglycerides (1:1) or as long-chain triglycerides alone in 10 or 20% fat emulsions or as glucose alone in a control group for 7 days. After surgery, an initial decrease of all plasma lipoprotein components was followed by a different behavior of glyceride-glycerol, cholesterol, phospholipids, and apolipoproteins. Glyceride-glycerol in very-low-density lipoproteins and high-density lipoproteins is increasing during infusion of fat emulsions and decreasing during overnight interruption of infusions. After the 7-day infusion period, there was no significant difference in very-low-density lipoprotein glyceride-glycerol as compared with the values before different infusions, Low-density lipoprotein cholesterol is reaching and exceeding preoperative concentrations between the 4th and the 7th day, most during infusion of 10% fat emulsion and especially due to an increase of free cholesterol, High-density lipoprotein cholesterol and apolipoprotein A-I reach preoperative levels during infusion of fat emulsions but not with glucose alone, Higher than preoperative values are reached in phospholipids with all fat infusions already on day 4, Abnormal lipoprotein X occurred least with the medium-chain/long-chain triglyceride 20% fat-infusion. This fat emulsion is suggested as having the best normalizing effect on plasma lipoproteins and best tolerance in patients after surgery

TLR ligands, but not modulators of histone modifiers, can induce the complex immune response pattern of endotoxin tolerance in mammary epithelial cells

Excessive stimulation of the TLR4 axis through LPS reduces the expression of some cytokine genes in immune cells, while stimulating the expression of immune defense genes during a subsequent bacterial infection. This endotoxin tolerance (ET) is mediated via epigenetic mechanisms. Priming the udder of cows with LPS was shown to induce ET in mammary epithelial cells (MEC), thereby protecting the udder against reinfection for some time. Seeking alternatives to LPS priming we tried to elicit ET by priming MEC with either lipopeptide (Pam2CSK4) via the TLR2/6 axis or inhibitors of histone-modifying enzymes. Pre-incubation of MEC with Pam2CSK4 enhanced baseline and induced expression of bactericidal (beta-defensin;SLPI) and membrane protecting factors (SAA3, TGM3), while reducing the expression of cytokine-and chemokine-encoding genes (TNF, IL1 beta) after a subsequent pathogen challenge, the latter, however, not as efficiently as after LPS priming. Pre-treating MEC with various inhibitors of histone H3 modifiers (for demethylation, acetylation or deacetylation) all failed to induce any of the protective factors and only resulted in some dampening of cytokine gene expression after the re-challenge. Hence, triggering immune functions via the TLR axis, but not through those histone modifiers, induced the beneficial phenomenon of ET in MEC

Activity of everolimus (RAD001) in relapsed and/or refractory multiple myeloma: a phase I study

The mammalian target of rapamycin plays an important role in multiple myeloma. The allosteric mammalian target of rapamycin inhibitor everolimus has long been approved for immunosuppression and has shown activity in certain cancers. This investigator-initiated phase I trial explored the use of everolimus in relapsed and/or refractory multiple myeloma patients who had received two or more lines of prior treatment. Following a dose-escalation design, it called for a fixed dose of oral everolimus. Blood drug levels were monitored and the biological activity of everolimus was evaluated in bone marrow. Seventeen patients were enrolled (age range, 52 to 76 years). All had been previously treated with stem cell transplantation and proteasome inhibitors and almost all with immunomodulatory drugs. No dose-limiting toxicity was observed and the intended final daily dose of 10 mg was reached. Only one severe adverse event was assessed as possibly related to the study drug, namely atypical pneumonia. Remarkably few infections were observed. Although the trial was mainly designed to evaluate feasibility, anti-myeloma activity, defined as clinical benefit, was documented in ten of 15 evaluable patients at every dose level including eight patients with stable disease, one patient with minor remission and one with partial remission. However, the median time to progression was 90 days (range, 13 to 278 days). The biomarker study documented on-target activity of everolimus in malignant plasma cells as well as the microenvironment. The observed responses are promising and allow further studies to be considered, including those testing combination strategies addressing escape pathways

Activity of everolimus (RAD001) in relapsed and/or refractory multiple myeloma: a phase I study

The mammalian target of rapamycin plays an important role in multiple myeloma. The allosteric mammalian target of rapamycin inhibitor everolimus has long been approved for immunosuppression and has shown activity in certain cancers. This investigator-initiated phase I trial explored the use of everolimus in relapsed and/or refractory multiple myeloma patients who had received two or more lines of prior treatment. Following a dose-escalation design, it called for a fixed dose of oral everolimus. Blood drug levels were monitored and the biological activity of everolimus was evaluated in bone marrow. Seventeen patients were enrolled (age range, 52 to 76 years). All had been previously treated with stem cell transplantation and proteasome inhibitors and almost all with immunomodulatory drugs. No dose-limiting toxicity was observed and the intended final daily dose of 10 mg was reached. Only one severe adverse event was assessed as possibly related to the study drug, namely atypical pneumonia. Remarkably few infections were observed. Although the trial was mainly designed to evaluate feasibility, anti-myeloma activity, defined as clinical benefit, was documented in ten of 15 evaluable patients at every dose level including eight patients with stable disease, one patient with minor remission and one with partial remission. However, the median time to progression was 90 days (range, 13 to 278 days). The biomarker study documented on-target activity of everolimus in malignant plasma cells as well as the microenvironment. The observed responses are promising and allow further studies to be considered, including those testing combination strategies addressing escape pathways

Estimated physical activity in Bavaria, Germany, and its implications for obesity risk: Results from the BVS-II Study

BACKGROUND: Adequate physical activity (PA) is considered as a key factor in the fight against the obesity epidemic. Therefore, detailed description of the actual PA and its components in the population is necessary. Additionally, this study aims to investigate the association between PA and obesity risk in a representative population sample in Bavaria, Germany. METHODS: Data from 893 participants (age 13–80 years) of the Bavarian Food Consumption Survey II (BVS II) were used. In each participant, three computer-based 24-hour recalls were conducted by telephone assessing type and duration of PA in the domains occupation, sports, other strenuous leisure time activities (of mostly moderate intensity) as well as TV/PC use in leisure time and duration of sleeping. After assigning metabolic equivalents (METs) to each activity, estimates of energy expenditure (MET*h) and total daily PA level (PAL(est.)) were calculated. In a subgroup of adults (n = 568) with anthropometric measurements logistic regression models were used to quantify the impact of PA on obesity risk. RESULTS: Estimated average PA in women and men was 38.5 ± 5.0 and 40.6 ± 9.3 MET*h/d, respectively, corresponding to PAL(est. )values of 1.66 ± 0.22 and 1.75 ± 0.40. Obese subjects showed lower energy expenditure in the categories sports, occupation, and sleeping, while the time spent with TV/PC during leisure time was highest. This is confirmed in logistic regression analyses revealing a statistically significant association between obesity and TV/PC use during leisure time, while sports activity was inversely related to obesity risk. Overall, less than 1/3 of the study participants reached the recommended PAL of ≥ 1.75. Subjects within the recommended range of PA had an about 60 % (odds ratio = 0.43; 95% CI: 0.21–0.85) reduced risk of obesity as compared to inactive subjects with a PAL(est. )<1.5. CONCLUSION: Based on the results of short-term PA patterns, a major part of the Bavarian adult population does not reach the recommendations (PAL>1.75; moderate PA of > 30 min/d). Despite the limitations of the study design, the existing associations between sports activity, TV/PC use and obesity risk in this population give further support to the recommendation of increasing sports activity and reducing sedentary behaviour in order to prevent rising rates of obesity

Early transcriptional events in the udder and teat after intra-mammary Escherichia coli and Staphylococcus aureus challenge

Intra-mammary bacterial infections can result in harmful clinical mastitis or subclinical mastitis with persistent infections. Research during the last decades closely examined the pathophysiology of inflamed udders. Initial events after pathogen perception but before the onset of mastitis have not been examined invivo. The objective of this study was to develop a mastitis model in cows by monitoring initial transcriptional pathogen-specific host response before clinical signs occur. We applied a short-term infection model to analyse transcripts encoding chemokines, cytokines and antimicrobial molecules in the teat cistern (TC) and lobulo-alveolar parenchyma (LP) up to 3h after challenge with E. and Staphylococcus aureus. Both pathogens elicited an immune reaction by 1h after challenge. Escherichia coli induced all analysed factors (CCL20, CXCL8, TNF, IL6, IL12B, IL10, LAP, S100A9);however, S. aureus failed to induce IL12B, IL10, LAP and S100A9 expression. The E. coli-induced up-regulation was 25-105 times greater than that after S. aureus challenge. Almost all the responses were restricted to the TC. The short-term mastitis model demonstrates that a divergent pathogen-specific response is generated during the first h. It confirms that the first transcripts are generated in the TC prior to a response in the LP

Determination of Total Homocysteine in Human Plasma by Isocratic High-Performance Liquid Chromatography

Peer Reviewe

Evidence-based guideline of the German Nutrition Society: fat intake and prevention of selected nutrition-related diseases

As nutrition-related chronic diseases have become more and more frequent, the importance of dietary prevention has also increased. Dietary fat plays a major role in human nutrition, and modification of fat and/or fatty acid intake could have a preventive potential. The aim of the guideline of the German Nutrition Society (DGE) was to systematically evaluate the evidence for the prevention of the widespread diseases obesity, type 2 diabetes mellitus, dyslipoproteinaemia, hypertension, metabolic syndrome, coronary heart disease (CHD), stroke, and cancer through the intake of fat or fatty acids. The main results can be summarized as follows: it was concluded with convincing evidence that a reduced intake of total and saturated fat as well as a larger intake of polyunsaturated fatty acids (PUFA) at the expense of saturated fatty acids (SFA) reduces the concentration of total and low-density lipoprotein cholesterol in plasma. Furthermore, there is convincing evidence that a high intake of trans fatty acids increases risk of dyslipoproteinaemia and that a high intake of long-chain polyunsaturated n-3 fatty acids reduces the triglyceride concentration in plasma. A high fat intake increases the risk of obesity with probable evidence when total energy intake is not controlled for (ad libitum diet). When energy intake is controlled for, there is probable evidence for no association between fat intake and risk of obesity. A larger intake of PUFA at the expense of SFA reduces risk of CHD with probable evidence. Furthermore, there is probable evidence that a high intake of long-chain polyunsaturated n-3 fatty acids reduces risk of hypertension and CHD. With probable evidence, a high trans fatty acid intake increases risk of CHD. The practical consequences for current dietary recommendations are described at the end of this article