2,252 research outputs found

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

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    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

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    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

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    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

    Get PDF
    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

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    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
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