1,721,133 research outputs found
ESPEN practical guideline on clinical nutrition in hospitalized patients with acute or chronic kidney disease
Full text linkBackground and aims: Hospitalized patients often have acute kidney disease (AKD) or chronic kidney disease (CKD), with important metabolic and nutritional consequences. Moreover, in case kidney replacement therapy (KRT) is started, the possible impact on nutritional requirements cannot be neglected. On this regard, the present guideline aims to provide evidence-based recommendations for clinical nutrition in hospitalized patients with KD. Methods: The standard operating procedure for ESPEN guidelines was used. Clinical questions were defined in both the PICO format, and organized in subtopics when needed, and in non-PICO questions for the more general topics. The literature search was from January 1st, 1999 until January 1st, 2020. Each question led to one or more recommendation/statement and related commentaries. Existing evidence was graded, as well as recommendations and statements were developed and agreed upon in a multistage consensus process. Results: The present guideline provides 32 evidence-based recommendations and 8 statements, defining how to assess nutritional status, how to define patients at risk, how to choose the route of feeding, and how to integrate nutrition with KRT. In the final online voting, a strong consensus was reached in 84% at least of recommendations and 100% of statements. Conclusion: The presence of KD in hospitalized patients identifies a highly heterogeneous group of subjects with widely varying nutrient needs and intakes. Considering the high nutritional risk related with this clinical condition, an individualized approach consisting of nutritional status evaluation and monitoring, frequent evaluation of nutritional requirements, and careful integration with KRT should be planned to avoid both underfeeding and overfeeding. Practical recommendations and statements were developed, aiming at defining suggestions for everyday clinical practice in the individualization of nutritional support in this patient setting. Literature areas with scarce or without evidence were also identified, thus requiring further basic or clinical research
A negative impact of recent weight loss on in-hospital mortality is not modified by overweight and obesity
Full text linkBACKGROUND: Obesity [Body Mass Index (BMI) > 30 kg/m2] is a risk factor for disease conditions enhancing hospitalization and mortality risks, but higher BMI was paradoxically reported to reduce mortality in several acute and chronic diseases. Unintentional weight loss (WL) is conversely associated with disease development and may worsen patient outcome, but the impact of weight loss and its interaction with obesity in modulating risk of death in hospitalized patients remain undefined. METHODS: We investigated the ESPEN nutritionDay database of non-critically ill hospitalized patients to assess the impact of self-reported 3-month WL (WL1:2.5-6.6%; WL2: 6.6-12.6%, WL3: >12.6%) and its interaction with BMI in modulating 30-day in-hospital mortality. Multivariate Cox regression was used to estimate hazard ratios (HR), with stable weight (WL0) as reference category. RESULTS: In 110835 nDay patients, 30-day mortality increased with increasing WL. Male gender, increasing disease severity index PANDORA score (age, nutrient intake, mobility, fluid status, cancer and main patient group) and not having had surgery also predicted 30-day mortality. HR for 30-day mortality remained significantly higher compared to WL0 for WL2 and WL3 after multiple adjustment. Adjusted HR and its increments through increasing weight loss categories were comparable in lean (BMI30 kg/m2). Impact of gender, PANDORA score and surgery on 30-day mortality were conversely comparable in the three BMI groups. CONCLUSIONS: These results indicate that self-reported WL could represent a relevant prognostic factor in every hospitalized patient. Overweight and obesity per se have no protective impact against WL-associated mortality
ESPEN practical guideline: Nutritional support for polymorbid medical inpatients.
No full textBACKGROUND
Disease-related malnutrition in polymorbid medical inpatients is a highly prevalent syndrome associated with significantly increased morbidity, disability, short- and long-term mortality, impaired recovery from illness, and healthcare costs.
AIM
As there are uncertainties in applying disease-specific guidelines to patients with multiple conditions, our aim was to provide evidence-based recommendations on nutritional support for the polymorbid patient population hospitalized in medical wards.
METHODS
The 2023 update adheres to the standard operating procedures for ESPEN guidelines. We undertook a systematic literature search for 15 clinical questions in three different databases (Medline, Embase and the Cochrane Library), as well as in secondary sources (e.g., published guidelines), until July 12th, 2022. Retrieved abstracts were screened to identify relevant studies that were used to develop recommendations (including SIGN grading), which was followed by submission to Delphi voting. Here, the practical version of the guideline is presented which has been shortened and equipped with flow charts for patients care.
RESULTS
32 recommendations (7× A, 11× B, 10× O and 4× GPP), which encompass different aspects of nutritional support were included from the scientific guideline including indication, route of feeding, energy and protein requirements, micronutrient requirements, disease-specific nutrients, timing, monitoring and procedure of intervention. Here, the practical version of the guideline is presented which has been shortened and equipped with flow charts for patients care.
CONCLUSIONS
Recent high-quality trials have provided increasing evidence that nutritional support can reduce morbidity and other complications associated with malnutrition in polymorbid patients. The timely screening of patients for risk of malnutrition at hospital admission followed by individualized nutritional support interventions for at-risk patients should be part of routine clinical care and multimodal treatment in hospitals worldwide. Use of this updated practical guideline offers an evidence-based nutritional approach to polymorbid medical inpatients and may improve their outcomes
Aktivierung humaner intestinaler Mastzellen durch Stammzellfaktor: Hochregulation der Zytokinexpression und Rolle der MAP Kinase ERK
Full text linkRolle des Plasminogen-Aktivator-Inhibitor (PAI-1) in der Pathogenese von Fruktose-induzierter nichtalkoholischer Fettlebererkrankung (NAFLD)
No full textNon-alcoholic fatty liver disease (NAFLD), a liver disease frequently associated with obesity, type 2 diabetes and dyslipidemia has become a worldwide health problem during the last decades. Results of recent studies suggest that a diet rich in fructose may also be a risk factor for the development of NAFLD. Results of our own group but also other group suggest that TNFα and PAI-1 may be involved in the development of NAFLD in rodents but also humans. Therefore, the aim of the present study was to investigate the role TNFα and PAI-1 in the onset of fructose-induced NAFLD in a mouse model as well as in human NAFLD patients. The specific aims were
1) Are TNFR1-/- mice protected from fructose-induced NAFLD? If yes, what are the molecular mechanisms involved?
TNFR1 -/- and wild-type mice were either fed 30% fructose solution or tap water. Chronic fructose feeding caused a significant ~5-fold increase in triglyceride accumulation and neutrophil infiltration in livers of wild-type mice and an ~8-fold increase in plasma alanine aminotransferase (ALT) levels in comparison to control mice. Similar effects of fructose feeding were not found in TNFR 1-/- mice. Indeed, the protective effect of the tumor necrosis factor receptor 1 (TNFR1) deletion against the onset of fructose-induced steatosis was associated with decreased sterol regulatory element-binding protein 1 (SREBP-1), fatty acid synthase (FAS) and plasminogen activator inhibitor 1 (PAI-1) expression in the liver. Furthermore, the protective effect was also associated with protection against alterations markers of insulin signaling cascade (e.g. adenosine monophosphate-activated protein kinase (AMPK), protein kinase B (Akt) levels). However, markers of hepatic lipid peroxidation, inducible nitric oxide synthase (iNOS) protein and adenosine triphosphate (ATP) levels were similar between wild-type and TNFR1 -/- mice fed fructose. Taken together, these data suggest that TNFα plays a casual role in the onset of fructose-induced liver damage as well as insulin resistance in mice through signaling cascades downstream of TNFR1.
2) Are PAI-1-/- mice protected from fructose-induced NAFLD? And if so, what are the molecular mechanisms involved?
To address if PAI-1 is also a critical factor in the onset of fructose-induced NAFLD, PAI-1-/- and wild-type mice were either fed a fructose solution or tap water. Chronic fructose feeding in wild-type mice caused a marked increase in hepatic triglycerides, PAI-1 expression and plasma ALT levels in comparison to water controls. A similar effect of fructose feeding was not found in PAI-1-/- mice. PAI-1-/- mice fed fructose were protected from hepatic steatosis despite similar portal endotoxin levels, alterations of markers of insulin resistance and hepatic TNFα protein levels between fructose fed groups. The protective effect of the loss of PAI-1 against the onset of fructose-induced steatosis was associated with a significant increase in phospho-cMet, phospho Akt, expression of apolipoprotein B (ApoB) and activity of microsomal triglyceride transfer protein (MTTP) in livers of PAI-1-/- mice in comparison to fructose fed wild-type mice. Moreover, in PAI-1-/- mice expression of CD1d and markers of CD1d-reactive iNKT cells were markedly higher than in wild-type mice; however, expression of markers of activation of CD1d-reactive iNKT cells (e.g. interleukin 15 (IL-15) and interferon γ (INFγ)) were only found to be increased in livers of fructose fed PAI-1-/- mice. Taken together, these data suggest that PAI-1 plays a causal role in mediating the early phase of fructose-induced liver damage in mice through signalling cascades down-stream of Kupffer cells and TNFα.
3) Are molecular mechanisms identified in mouse studies also relevant to human situation?
To determine if the alterations found in livers of animals with NAFLD are also relevant in humans with NAFLD, markers of lipid peroxidation, insulin signaling and number of iNKT cells were determined in 6 controls and 11 NAFLD patients.4-hydroxynonenal (4-HNE) protein adducts levels were significantly higher in livers of NAFLD patients whereas expression of insulin receptor substrate (IRS-1) was reduced by ~80 % in comparison to controls. PAI-1 protein levels primarily found in hepatocytes was significantly higher in NAFLD patients; however, hepatic CD1d and MTTP mRNA expression did not differ between groups.
Hepatic c-Met and BCL-2l mRNA expressions were significantly lower in NAFLD patients in comparison to controls and number of CD3ζ positive cells was higher. In contrast, expression of iNKT cell markers (e.g. IL-4 and IL-15) was significantly lower in livers of patients with NAFLD when compared with controls.Taken together, the present study suggests that the molecular mechanism involved in the progression of NAFLD is similar in both rodents and humans. Furthermore, TNFα and PAI-1 may be considered as therapeutic targets for NAFLD.Die nicht-alkoholbedingte Fettlebererkrankung (NAFLD) ist eine Lebererkrankung, die häufig mit Übergewicht, Typ-2 Diabetes und Dyslipidämie assoziiert ist und somit in den letzten Jahrzehnten zu einem weltweiten Gesundheitsproblem wurde. Ergebnisse neuer Studien legen nahe, dass eine fruktose reiche Ernährung ein Risikofaktor für die Entwicklung von NAFLD ist. Nicht nur Ergebnisse der eigenen Arbeitsgruppe, sondern auch anderer Arbeitsgruppen legen nahe, dass TNFα und PAI-1 in der Entwicklung von NAFLD in Tiermodell aber auch Menschen beteiligt sein können. Vor diese HIntergrund war es das Ziel der vorliegenden Arbeit, die Rolle von TNFα und PAI-1 in der Entstehung einer fruktose-induzierten NAFLD sowohl im Mausmodell als auch bei Patienten mit NAFLD zu untersuchen.
Die spezifischen Ziele waren:
1) Sind TNFR1-/- Mäuse vor der fruktose-induzierten NAFLD geschützt? Wenn ja, was sind die beteiligten molekularen Mechanismen?
Tumornekrosefaktor-Rezeptor 1 (TNFR1)-/- und Wildtyp-Mäuse wurden entweder mit einer 30%igen Fruktose-Lösung oder Wasser gefüttert. Die chronische Fütterung mit Fruktose führte zu einem signifikanten, ~5-fachen Anstieg der Triglyceridkonzentration und Neutrophileninfiltration in der Leber von Wildtypmäusen, sowie einem ~8-fachen Anstieg der Konzentration der Alanin-Aminotransferase (ALT) im Plasma im Vergleich zu den Kontroll mäusen. Ähnliche Effekte konnten in TNFR1-/- Mäusen nach der Fütterung mit Fruktose nicht nachgewiesen werden. Die protektive Wirkung des Verlustes TNFR1 gegenüber der fruktose-induzierten Steatose mit einer Verminderung der Expression des sterol regulatory element-binding protein 1 (SREBP-1), der Fettsäure-Synthase (FAS) und von PAI-1 in der Leber assoziiert. Darüber hinaus waren TNFR1-/- Mäuse auch vor veränderungen von
Markern der Insulin-Signalkaskade, wie der Adenosin-monophosphat-aktivierten Proteinkinase (AMPK) und der Proteinkinase B (Akt) geschützt. Jedoch fanden sich nur geringe Unterschiede in der hepatischen Lipidperoxidation, der Konzentration der induzierbaren Stickstoffmonoxid-Synthase (iNOS) und des Adenosintriphosphats (ATP) zwischen Wildtyp- und TNFR1-/- Mäusen nach Fruktosefütterung. Insgesamt, weisen die Ergebnisse darauf hin, dass TNFα eine wasentliche Rolle in der Entstehung von fructose-induzierte Leberschäden sowie der Insulin-Resistenz bei Mäusen über dem TNFR1 nachgeschalteten Signalkaskaden spielt.
2) Sind PAI-1-/- Mäuse vor der fruktose-induzierten NAFLD geschützt? Wenn ja, was sind die beteiligten molekularen Mechanismen?
Um zu untersuchen ob PAI-1 ebenfalls ein kritischer Faktor bei der Entstehung von fruktose-induzierter NAFLD ist, wurden PAI-1-/- sowie Wildtyp-Mäuse entweder mit einer Fruktoselösung oder Wasser gefüttert. Die chronische Fütterung mit Fruktose führte in Wildtyp-Mäusen zu einem deutlichen Anstieg der Triglycerid-Konzentration in der Leber, der Expression von PAI-1 sowie der Plasma ALT-Spiegel im Vergleich zu den Wasserkontrollen. Eine ähnliche Wirkung der Fruktosefütterung auf PAI-1-/- Mäuse wurde nicht gefunden. So waren PAI-1-/- Mäuse vor der Lebersteatose trotz ähnlich hoher portaler Endotoxinspiegel, Insulinresistenz und hepatischer TNFα Konzentrationen geschützt. Die schützende Wirkung des PAI-1-Verlustes gegenüber der Entstehung von fruktose-induzierter Steatose war mit einer signifikanten Zunahme der Konzentration an phospho-c-Met, phospho Akt, der Expression von Apolipoprotein B (ApoB) sowie der Aktivität des mikrosomalen Triglyceridtransferporteins (MTTP) in den Lebern von PAI-1-/- Mäusen im Vergleich zu fruktose-gefütterten Wildtyp-Mäusen assoziert. Darüber hinaus war die Expression von CD1d und Markern von CD1d-reaktiven NKT Zellen in PAI-1-/- Mäusen deutlich höher als in den Wildtyp-Mäusen. Allerdings war die Expression der Aktivierungsmarker von CD1d-reaktiven NKT Zellen (z. B. Interleukin (IL) 15 und Interferon (IFN) γ) nur in den Lebern von fruktose-gefütterten PAI-1-/- Mäusen erhöht. Insgesamt deuten die Daten darauf hin, dass PAI-1 eine kausale Rolle in der Vermittlung der frühen Phase der fructose-induzierten Leberschädigung bei Mäusen über Signalkaskaden ?down-stream? der Kupffer-Zellen und von TNFα spielt.
3) Sind die in Mausstudien identifizierten, molekularen Mechanismen auf den Menschen übertragbar?
Um festzustellen, ob die Veränderungen in der Leber von Tieren mit NAFLD auch für die Entstehung der NAFLD bei Menschen relevant sind, wurden Marker der Lipidperoxidation, Insulin-Signalkaskade und die Anzahl der iNKT-Zellen in 6 Kontrollen und 11 Patienten mit NAFLD bestimmt. Das Niveau an 4-HNE Proteinaddukten war in den Lebern der NAFLD-Patienten signifikant erhöht, wohingegen die Expression von Insulin-Rezeptor-Substrat (IRS-1) im Vergleich zu den Kontrollen um ~80 % reduziert war. Die Konzentration an PAI-1 Protein war in Patienten mit NAFLD signifikant höher wohingegen die mRNA-Expression von hepatischem CD1d und MTTP sich nicht zwischen den verschiedenen Gruppen unterschied. Die Hepatische c-Met sowie die BCL-21 mRNA Expression war bei NAFLD-Patienten signifikant niedriger im Vergleich zu den Kontrollen, wohingegen die Anzahl der CD3ζ-positiven Zellen erhöht war. Im Gegensatz dazu war die Expression der iNKT-Zellmarker IL-4 und IL-15 bei Patienten mit NAFLD signifikant niedriger als in den Lebern der Kontrollen. Insgesamt deuten die Ergebinesse der vorliegende Studie darauf hin, dass die bei der Progression der NAFLD beteiligten molekularen Mechanismen sowohl bei Nagern als auch bei Menschen ähnlich sind. Ferner können TNFα und PAI-1 in der Therapie der NAFLD von Bedeutung sein
Regulation der Fc[Epsilon]RI vermittelten Zytokingenexpression in humanen intestinalen Mastzellen
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Einfluss einer Glutamin-Supplementation auf den Ernährungsstatus, den Krankheitsverlauf und die intestinale Schleimhautintegrität bei parenteral ernährten Patienten
Full text linkInteractions between human intestinal mast cells and human intestinal fibroblasts
No full textFibroblasts (FB) play a central role in the pathogenesis of fibrosis since they are the major source of extracellular matrix proteins. However, the regulation of extracellular matrix production in fibroblasts, the mechanisms that lead to loss of control of extracellular matrix homeostasis during chronic inflammation and the role of human intestinal mast cells are still not fully understood.
Mast cells are key effector cells in allergic reactions but also involved in host defense and tissue remodeling processes such as wound healing, angiogenesis, and fibrogenesis. The group pf Prof. Bischoff has shown previously that human intestinal fibroblasts suppress apoptosis in human intestinal MC independent of the known human mast cell growth factors stem cell factor interleukin-3, interleukin-4, and nerve growth factor.In this work I could show that the effects of fibroblasts on mast cells are mediated by interleukin-6. The molecular crosstalk between human mast cells and human fibroblasts, both isolated and purified from intestinal tissue was analyzed. Mast cells survival in the presence of fibroblasts could be blocked using an anti-interleukin-6 antibody. Mast cells incubated with interleukin-6 survived for up to 3 weeks. Intestinal fibroblasts produced interleukin-6 upon direct stimulation by mast cells in co-culture or by mast cell mediators such as tumor necrosis factor alpha, interleukin-1 beta, tryptase or histamine. Moreover, fibroblasts stimulated by mast cell mediators produce the antifibrotic enzyme matrix metalloproteinase-1. Matrix metalloproteinase-1 should be considered as multifunctional molecule since it participates not only in the turnover of collagen fibrils in the extracellular space but also in the cleavage of a number of non-matrix substrates and cell surface molecules suggesting a role in the regulation of cellular behaviour. Noteworthy, fibroblasts co-cultured with mast cells or treated with matrix metalloproteinase-1 lost confluence. Matrix metalloproteinase-1 expression in fibroblasts triggered by mast cells was dependent on the MEK/ERK cascade as shown by inhibitor experiments.
In conclusion, this study show that mast cells mediators stimulate fibroblasts to produce interleukin-6, and, vice versa, fibroblasts derived interleukin-6 supports mast cells survival. Furthermore, mast cell mediators induce expression of matrix metalloproteinase-1 in fibroblasts, a key enzyme in fibrolysis, which in turn leads to lost of confluence of cultured fibroblasts. Taken together the results of my work suggest that mast cells accumulating at sites of fibrosis rather limite than promote fibrogenesis.Fibroblasten spielen eine zentrale Rolle in der Pathogenese von Fibrose, da sie die Hauptquelle der extrazellulären Matrixproteine sind. Allerdings ist die Regulation der Fibroblasten bei der Bildung der extrazellulären Matrix, der Mechanismus der zum Kontrollverlusst der extrazellulären Matrix Homeostase bei der chronischen Entzündung führt, und die Funktion, die humane Darmmastzellen dabei spielen, noch nicht verstanden.
Mastzellen besitzen eine Schlüsselrolle bei allergischen Reaktionen, sind aber auch an der Immunabwehr, bei Gewebeneubildungsprozessen wie z.B. der Wundheilung, der Angiogenese und der Fibrogenese beteiligt. Die Arbeitgruppe von Prof. Bischoff konnte bereits zeigen, dass humane Darmfibroblasten Apoptose in humanen Darmmastzellen unabhängig von den bekannten Mastzell-Wachstumsfaktoren Stem Cell Factor, IL-3, IL-4 und Nerve Growth Factor unterdrücken. In meiner Arbeit konnte ich nun zeigen, dass die Effekte von Fibroblasten auf Mastzellen von IL-6 vermittelt werden. Es wurden die molekularen Interaktionen zwischen humanen Mastzellen und humanen Fibroblasten, beide isoliert und aufgereinigt aus Darmgewebe, untersucht. Das Überleben der Mastzellen bei Anwesenheit von Fibroblasten konnte mit einem anti-IL-6 Antikörper verhindert werden. Mastzellen, die mit IL-6 inkubiert wurden, überlebten bis zu 3 Wochen, genauso wie Mastzellen, die mit Fibroblasten co-kultiviert wurden. Stimuliert durch die Co-Kultivierung mit Mastzellen oder durch Mastzellmediatoren, produzieren Darmfibroblasten IL-6. Außerdem bilden Fibroblasten nach Stimulation mit Mastzellmediatoren das antifibrotische Enzym Matrixmetalloproteinase-1. Matrixmetalloproteinase-1 wird als multifunktionelles Molekül betrachtet, da es nicht nur am Umsatz der Collagenfasern in der extrazellulären Matrix beteiligt ist, sondern auch an der Teilung zahlreicher ?Nicht-Matrix?-Substrate und Zelloberflächenmoleküle, weshalb ihm eine Rolle bei der Regulation der Zellfunktionen zugeschrieben wird. Erstaunlicherweise verlieren Fibroblasten, die mit Mastzellen co-kultiviert, oder mit Matrixmetalloproteinase-1 behandelt werden, ihre Konfluenz. Die von Mastzellen in Fibroblasten ausgelöste Matrixmetalloproteinase-1 Expression, hängt von dem MEK/ERK Signalweg ab, wie unsere Inhibitionsexperimente zeigten.
Zusammenfassend kann gesagt werden, dass die vorliegende in vitro Studie zeigt, dass Mastzellmediatoren Fibroblasten stimulieren IL-6 zu bilden und umgekehrt die Bildung von IL-6 durch Fibroblasten das Überleben der Mastzellen fördert. Außerdem induzieren Mastzellmediatoren die Expression von Matrixmetalloproteinase-1 in Fibroblasten. Die Ergebnisse meiner Arbeit deuten darauf hin, dass Mastzellen, die an fibrotischen Stellen akkumulieren, Fibrogenese eher unterdrücken als Fibrogenese unterstützen
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