329 research outputs found
Clofibrate treatment in pigs: Effects on parameters critical with respect to peroxisome proliferator-induced hepatocarcinogenesis in rodents
BACKGROUND: In rodents treatment with fibrates causes hepatocarcinogenesis, probably as a result of oxidative stress and an impaired balance between apoptosis and cell proliferation in the liver. There is some debate whether fibrates could also induce liver cancer in species not responsive to peroxisome proliferation. In this study the effect of clofibrate treatment on peroxisome proliferation, production of oxidative stress, gene expression of pro- and anti-apoptotic genes and proto-oncogenes was investigated in the liver of pigs, a non-proliferating species. RESULTS: Pigs treated with clofibrate had heavier livers (+16%), higher peroxisome counts (+61%), higher mRNA concentration of acyl-CoA oxidase (+66%), a higher activity of catalase (+41%) but lower concentrations of hydrogen peroxide (-32%) in the liver than control pigs (P < 0.05); concentrations of lipid peroxidation products (thiobarbituric acid-reactive substances, conjugated dienes) and total and reduced glutathione in the liver did not differ between both groups. Clofibrate treated pigs also had higher hepatic mRNA concentrations of bax and the proto-oncogenes c-myc and c-jun and a lower mRNA concentration of bcl-X(L )than control pigs (P < 0.05). CONCLUSION: The data of this study show that clofibrate treatment induces moderate peroxisome proliferation but does not cause oxidative stress in the liver of pigs. Gene expression analysis indicates that clofibrate treatment did not inhibit but rather stimulated apoptosis in the liver of these animals. It is also shown that clofibrate increases the expression of the proto-oncogenes c-myc and c-jun in the liver, an event which could be critical with respect to carcinogenesis. As the extent of peroxisome proliferation by clofibrate was similar to that observed in humans, the pig can be regarded as a useful model for investigating the effects of peroxisome proliferators on liver function and hepatocarcinogenesis
Effect of L-carnitine on the hepatic transcript profile in piglets as animal model
<p>Abstract</p> <p>Background</p> <p>Carnitine has attracted scientific interest due to several health-related effects, like protection against neurodegeneration, mitochondrial decay, and oxidative stress as well as improvement of glucose tolerance and insulin sensitivity. The mechanisms underlying most of the health-related effects of carnitine are largely unknown.</p> <p>Methods</p> <p>To gain insight into mechanisms through which carnitine exerts its beneficial metabolic effects, we fed piglets either a control or a carnitine supplemented diet, and analysed the transcriptome in the liver.</p> <p>Results</p> <p>Transcript profiling revealed 563 genes to be differentially expressed in liver by carnitine supplementation. Clustering analysis of the identified genes revealed that most of the top-ranked annotation term clusters were dealing with metabolic processes. Representative genes of these clusters which were significantly up-regulated by carnitine were involved in cellular fatty acid uptake, fatty acid activation, fatty acid β-oxidation, glucose uptake, and glycolysis. In contrast, genes involved in gluconeogenesis were down-regulated by carnitine. Moreover, clustering analysis identified genes involved in the insulin signaling cascade to be significantly associated with carnitine supplementation. Furthermore, clustering analysis revealed that biological processes dealing with posttranscriptional RNA processing were significantly associated with carnitine supplementation.</p> <p>Conclusion</p> <p>The data suggest that carnitine supplementation has beneficial effects on lipid and glucose homeostasis by inducing genes involved in fatty acid catabolism and glycolysis and repressing genes involved in gluconeogenesis.</p
Effects of broccoli extract and various essential oils on intestinal and faecal microflora and on xenobiotic enzymes and the antioxidant system of piglets
Objective: Since the ban of antibiotics as growth promoting feed additives in
the EU in 2006 research in alternatives has gained importance. Phytogenic feed
additives represent a heterogenous class of different plant derived substances
that are discussed to improve the health of farm animals by direct and
indirect antioxidant effects and by influencing microbial eubiosis in the
gastrointestinal tract. Consequently our study aimed to investigate the
influence of broccoli extract and the essential oils of tur- meric, oregano,
thyme and rosemary, as selected individual additives, on intestinal and faecal
microflora, on xenobiotic enzymes, and on the antioxidant system of piglets.
Methods: 48 four weeks old male weaned piglets were assigned to 6 groups of 8.
The piglets were housed individually in stainless steel pens with slatted
floor. The control group (Con) was fed a diet without an additive for 4 weeks.
The diet of group BE contained 0.15 g/kg sulforaphane in form of a broccoli
extract. 535, 282, 373 and 476 mg/kg of the essential oils of turmeric (Cuo),
oregano (Oo), thyme (To) and rosemary (Ro) were added to the diets of the
remaining 4 groups to stan-dardise supplementation to 150 mg/kg of the oils’
key terpene compounds ar-turmerone, carvacrol, thymol and 1,8-cineole. The
composition of bacterial microflora was examined by cultivating samples of
jejeunal and colonic mucosa and of faeces under specific conditions. The mRNA
expression of xenobiotic and antioxidant enzymes was determined by reversing
transcrip- tase real time detection PCR (RT-PCR). Total antioxidant status was
assayed using the Trolox Equivalent Antioxidant Capacity (TEAC), and lipid
peroxidation was determined by measuring thiobarbioturic acid reactive
substances (TBA- RS). Results: Compared to Con piglets all additives
positively influenced weight gain and feed conversion in week 1. Over the
whole trial period no significant differences in performance parameters
existed between the experimental groups. Compared to group Con performance of
Ro piglets was, however, slightly impaired. Com- pared to Con piglets Cuo, Oo
and To increased the ratio of Lactobacilli:E. coli attached to the jejunal
mucosa, whereas BE and Ro impaired this ratio slightly. In contrast in colonic
mucosa Ro improved Lactobacilli:E. coli ratio. In faecal samples an
improvement of Lactobacilli:E. coli ratio could be analysed for To and Ro. Ro
was the only additive that reduced the incidence rate of piglets tested
positive for enterotoxic E. coli (ETEC). All additives significantly increased
jejunal TEAC and reduced TBA-RS. In the liver BE, Cuo, Oo and To increased
TEAC in tendency and Ro significantly. Liver TBA-RS were slightly reduced by
all additives compared to Con piglets. Whereas the influence of BE, To and Ro
on jejunal TEAC mainly was derived from the induction of xenobiotic and
antioxidant enzymes (indirect antioxidant effects), Cuo and Oo influenced TEAC
by direct antioxidant effects. Discussion and Conclusions: Our results have
shown: That within the labiatae oils Oo and To have the potential to improve
performance slightly. That phytogenic substances have a small but not sig-
nificant influence on intestinal microflora. That phytogenic feed additives
up-regulate the anti- oxidant system of piglets either by direct or by
indirect antioxidant effects and that they may thereby improve health status.
That within the labiatae oils Oo has a high direct antioxidant potential
whereas Ro potently induces xenobiotic and antioxidant enzymes. That broccoli
extract is an attractive new phytogenic additive, improving antioxidant status
by indirect antioxidant effects. That defined combinations of selected
phytogenic substances may produce additive effects. That health promoting
effects of phytogenic additives in the future should be studied systematically
under the challenge with pathogenic microorganisms or food derived to-xins
OpARA – Open Access Repository and Archive: Archivierung und Publikation digitaler Forschungsdaten
Für Wissenschaftler der Technischen Universitäten Dresden und Bergakademie Freiberg, die ihre Forschungsdaten archivieren und publizieren möchten, steht seit Anfang 2018 der Dienst OpARA (Open Access Repository and Archive) als institutionelles Repositorium zur Verfügung. Wissenschaftler haben hier die Möglichkeit, ohne zusätzliche Kosten die Anforderungen der Guten Wissenschaftlichen Praxis an die langfristige sichere Aufbewahrung von Forschungsdaten (Archivierung über mindestens zehn Jahre) unkompliziert zu erfüllen. Der Dienst OpARA wird von den Rechenzentren der beiden Universitäten gemeinsam betrieben, die Daten werden lokal archiviert und optional publiziert.
Vor der Archivierung findet ein Begutachtungsprozess statt, um die fachliche und technische Qualität der Daten zu gewährleisten. Es wird dabei insbesondere die Dokumentation und Aufbereitung für Daten, die publiziert werden sollen, unter dem Aspekt einer guten Nachnutzbarkeit beurteilt und bei Bedarf unterstützt
Проектирование системы электроснабжения базы по обслуживанию нефтегазодобывающего месторождения
Выпускная квалификационная работа 136 с., 19 рис., 60 табл., 24 источника, 4 приложения.
Объектом исследования является ремонтно-механический цех базы по обслуживанию нефтегазодобывающего месторождения.
Цель работы: Проектирование системы электроснабжения базы по облуживанию нефтегазодобывающего месторождения. Экономическое обоснование принятых решений.
В процессе исследования произведен расчет нагрузок ремонтно-механического цеха и базы в целом с применением различных методов, выбор метода расчета производился на основе исходных данных, а также осуществлен выборThis graduate qualification work includes 136 p., 19 fig., 60 tables, 24 ones in list of references and 4 transcripts.
The subject of research is mechanical repair shop of upstream and gas production field operation base.
Work objective is energy supply system designing of upstream and gas production field operation base and its business case.
In the course of investigations there was estimated a load analysis of upstream and gas production field operation base and its mechanical repair shop by different methods, based on input data. Also there were steps of the equipment selection and its testing of several operations.
As a result of investigation the model of such base was engineered, and there was shown its commercial importance and ecological security.
Range of application: petro
Shortened Tracer Uptake Time in GA-68-DOTATOC-PET of Meningiomas Does Not Impair Diagnostic Accuracy and PET Volume Definition
Ga-68-DOTATOC-PET/MRI can affect the planning target volume (PTV) definition of meningiomas before radiosurgery. A shorter tracer uptake time before image acquisition could allow the examination of more patients. The aim of this study was to investigate if shortening uptake time is possible without compromising diagnostic accuracy and PET volume. Fifteen patients (f = 12; mean age 52 years (34-80 years)) with meningiomas were prospectively examined with dynamic [68Ga]Ga-68-labeled [DOTA0-Phe1-Tyr3] octreotide (Ga-68-DOTATOC)-PET/MRI over 70 min before radiosurgery planning. Meningiomas were delineated manually in the PET dataset. PET volumes at each time point were compared to the reference standard 60 min post tracer injection (p.i.) using the Friedman test followed by a Wilcoxon signed-rank test and Bonferroni correction. In all patients, the earliest time point with 100% lesion detection compared to 60 min p.i. was identified. PET volumes did not change significantly from 15 min p.i. (p = 1.0) compared to 60 min p.i. The earliest time point with 100% lesion detection in all patients was 10 min p.i. In patients with meningiomas undergoing Ga-68-DOTATOC-PET, the tracer uptake time can safely be reduced to 15 min p.i. with comparable PET volume and 100% lesion detection compared to 60 min p.i
Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study
Rationale
Steroid profiles in combination with a corticotropin stimulation test provide information about steroidogenesis and its functional reserves in critically ill patients.
Objectives
We investigated whether steroid profiles before and after corticotropin stimulation can predict the risk of in-hospital death in sepsis.
Methods
An exploratory data analysis of a double blind, randomized trial in sepsis (HYPRESS [HYdrocortisone for PRevention of Septic Shock]) was performed. The trial included adult patients with sepsis who were not in shock and were randomly assigned to placebo or hydrocortisone treatment. Corticotropin tests were performed in patients prior to randomization and in healthy subjects. Cortisol and precursors of glucocorticoids (17-OH-progesterone, 11-desoxycortisol) and mineralocorticoids (11-desoxycorticosterone, corticosterone) were analyzed using the multi-analyte stable isotope dilution method (LC–MS/MS). Measurement results from healthy subjects were used to determine reference ranges, and those from placebo patients to predict in-hospital mortality.
Measurements and main results
Corticotropin tests from 180 patients and 20 volunteers were included. Compared to healthy subjects, patients with sepsis had elevated levels of 11-desoxycorticosterone and 11-desoxycortisol, consistent with activation of both glucocorticoid and mineralocorticoid pathways. After stimulation with corticotropin, the cortisol response was subnormal in 12% and the corticosterone response in 50% of sepsis patients. In placebo patients (n = 90), a corticotropin-stimulated cortisol-to-corticosterone ratio > 32.2 predicted in-hospital mortality (AUC 0.8 CI 0.70–0.88; sensitivity 83%; and specificity 78%). This ratio also predicted risk of shock development and 90-day mortality.
Conclusions
In this exploratory analysis, we found that in sepsis mineralocorticoid steroidogenesis was more frequently impaired than glucocorticoid steroidogenesis. The corticotropin-stimulated cortisol-to-corticosterone ratio predicts the risk of in-hospital death.
Trial registration Clinical trial registered with www.clinicaltrials.gov Identifier: NCT00670254. Registered 1 May 2008, https://clinicaltrials.gov/ct2/show/NCT00670254
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