Fish oil-containing lipid emulsions in patients with sepsis

Lipid emulsions based on soybean oil have been an integral part of parenteral nutrition supplying n-6 fatty acids, with possible negative effects in critically ill patients. Newer lipid emulsions supply less n-6 fatty acids. In addition, fish oil-based lipids may be included in the lipid component of parenteral nutrition. While clinical benefits of lipid emulsions with a reduced fraction in n-6 lipids and the addition of fish oil have been described in postoperative patients, data are less clear in critically ill or septic patients. Recent data suggest that beneficial effects may be achieved when used early but clearly more data are needed to come to a definitive conclusion. The present commentary will highlight current data in critically ill and septic patients and the use of fish oil as a part of parenteral nutrition

Untersuchungen zur Pathovar-Prävalenz beim Escherichia coli- bedingten Durchfall neugeborener Saugferkel in ökologisch wirtschaftenden Ferkelerzeugerbetrieben

Saugferkeldurchfall ist eine Faktorenkrankheit, die durch Tierverluste, Wachstumsdepressionen und zusätzlichen therapeutischen Aufwand zu großen wirtschaftlichen Einbußen in der Ferkelproduktion führt. Im Zuge des vorgestellten Forschungsprojekts wurden 699 Kotproben von Saugferkeln mit Durchfall aus 258 Würfen von 18 ökologisch wirtschaftenden Ferkelerzeugerbetrieben auf enterotoxische Escherichia coli (ETEC), Clostridium (Cl.) perfringens, Rotaviren und Kokzidien untersucht. Außerdem wurden 369 Kotproben von Sauen und 419 Proben von gesunden Ferkeln auf Cl. perfringens untersucht. Eine Genotypisierung aller kulturell angezüchteten Cl. perfringens Isolate mittels RAPD-PCR sowie eine MLST von 8 Isolaten schlossen sich an. In 39,5% der erkrankten Würfe wurde Cl. perfringens Typ A nachgewiesen, welches damit der am häufigsten nachgewiesene Durchfallerreger war. 89,7% der Cl. perfringens Typ A Isolate wurden positiv auf das β2-Toxingen getestet. Rotaviren traten in 27,6% und Kokzidien in 20,0% der erkrankten Würfe auf, während ETEC mit 7,7% unerwartet selten diagnostiziert wurden. Cl. perfringens Typ C wurde in keiner Probe nachgewiesen. Auffällig ist, dass die Nachweisrate für Cl. perfringens Typ A bei gesunden Saugferkeln mit 58,9% über der bei erkrankten Saugferkeln liegt und dass nur 8,6% der Cl. perfringens Typ A Isolate von Sauen das β2-Toxingen tragen, welches in 94,2% aller Isolate von Saugferkeln (gesund und erkrankt) nachgewiesen wurde. Diese Erkenntnis deutet darauf hin, dass die Rolle der Sau als Infektionsquelle für die Saugferkel in Hinblick auf Cl. perfringens bisher überschätzt wurde. Die Genotypisierung der Cl. perfringens Typ A Isolate mittels RAPD offenbart eine hohe genetische Diversität der Isolate. Ferner geht aus einer Befragung der Betriebsleiter hervor, dass auf den meisten der teilnehmenden Betriebe erhebliche Defizite bei der Durchführung von Hygienemaßnahmen im Abferkelstall sowie Überwachung von Geburtsverlauf und Kolostrumaufnahme bestehen

Europas Potenziale im Zeichen der Krise

"Die Europäische Union (EU) steht im Jahr 2009 in Schlüsselbereichen ihrer Politik vor wichtigen Entscheidungen. Der Druck, gemeinsam nach Lösungen zu suchen, hat die Mitgliedstaaten der EU bereits näher zusammenrücken lassen – sei es mit Blick auf die Neugestaltung der transatlantischen Beziehungen, die Formulierung einer integrierten Energie- und Klimaschutzpolitik, die globale Finanz- und Wirtschaftskrise oder einen gemeinsamen wissenschafts- und forschungspolitischen Ansatz. Die Bewältigung all dieser Herausforderungen erfordert die Klärung grundlegender konzeptioneller Fragen. Europa benötigt Orientierung, einen Konsens über eine tragende Idee. Gelingt es der EU nicht, sich darauf zu verständigen, steht vieles auf dem Spiel. Es geht um Europas weltpolitische Mitverantwortung, seine Handlungsfähigkeit und seine Möglichkeit, Identität zu stiften. Europa braucht daher eine neue perspektivische Klarheit." (Autorenreferat

Increased expression of 5-hydroxytryptamine(2A/B) receptors in idiopathic pulmonary fibrosis: a rationale for therapeutic intervention

Background Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and limited responsiveness to available treatments. It is characterised by epithelial cell injury, fibroblast activation and proliferation and extracellular matrix deposition. Serotonin (5-hydroxytryptamine; 5-HT) induces fibroblast proliferation via the 5-HTR2A and 5-HTR2B receptors, but its pathophysiological role in IPF remains unclear. A study was undertaken to determine the expression of 5-HT receptors in IPF and experimental lung fibrosis and to investigate the effects of therapeutic inhibition of 5-HTR2A/B signalling on lung fibrosis in vivo and in vitro. Methods and results Quantitative RT-PCR showed that the expression of 5-HTR1A/B and 5-HTR2B was significantly increased in the lungs of patients with IPF (n = 12) and in those with non-specific interstitial pneumonia (NSIP, n = 6) compared with transplant donors (n = 12). The expression of 5-HTR2A was increased specifically in IPF lungs but not in NSIP lungs. While 5-HTR2A protein largely localised to fibroblasts, 5-HTR2B localised to the epithelium. To assess the effects of 5HTR(2A/B) inhibition on fibrogenesis in vivo, mice were subjected to bleomycin-induced lung fibrosis and treated with the 5-HTR2A/B antagonist terguride (or vehicle) in a therapeutic approach (days 14-28 after bleomycin). Terguride-treated mice had significantly improved lung function and histology and decreased collagen content compared with vehicle-treated mice. Functional in vitro studies showed that terguride is a potent inhibitor of transforming growth factor beta(1)- or WNT3a-induced collagen production. Conclusion The studies revealed an increased expression of 5-HTR2A specifically in IPF. Blockade of 5-HTR2A/B signalling by terguride reversed lung fibrosis and is thus a promising therapeutic approach for IPF

Human RELMβ is a mitogenic factor in lung cells and induced in hypoxia

AbstractRELMβ (resistin-like molecule) represents the most related human homologue of mouse RELMα, also known as hypoxic-induced mitogenic factor (HIMF). In this study, we isolated RELMβ cDNA from human lung tissue and performed regulatory and functional expression studies. RELMβ mRNA was upregulated in hypoxia in human lung A549 cell line as well as primary cultured adventitial fibroblasts and smooth muscle cells (SMC) of pulmonary arteries. Upon transfection of a RELMβ encoding expression plasmid into these cells, we observed significant induction of proliferation particularly in SMC and A549 cells, which could be blocked by phosphatidyl-inositol 3-kinase (PI3K) inhibitors LY294002 and wortmannin. The results suggest that human RELMβ may contribute to hypoxic-induced pulmonary vascular remodeling processes or hypoxia related fibrotic lung disease

Identification of proteins in laser-microdissected small cell numbers by SELDI-TOF and Tandem MS

BACKGROUND: Laser microdissection allows precise isolation of specific cell types and compartments from complex tissues. To analyse proteins from small cell numbers, we combine laser-microdissection and manipulation (LMM) with mass spectrometry techniques. RESULTS: Hemalaun stained mouse lung sections were used to isolate 500–2,000 cells, enough material for complex protein profiles by SELDI-TOF MS (surface enhanced laser desorption and ionization/time of flight mass spectrometry), employing different chromatographic ProteinChip(® )Arrays. Initially, to establish the principle, we identified specific protein peaks from 20,000 laser-microdissected cells, combining column chromatography, SDS-PAGE, tryptic digestion, SELDI technology and Tandem MS/MS using a ProteinChip(® )Tandem MS Interface. Secondly, our aim was to reduce the labour requirements of microdissecting several thousand cells. Therefore, we first defined target proteins in a few microdissected cells, then recovered in whole tissue section homogenates from the same lung and applied to these analytical techniques. Both approaches resulted in a successful identification of the selected peaks. CONCLUSION: Laser-microdissection may thus be combined with SELDI-TOF MS for generation of protein marker profiles in a cell-type- or compartment-specific manner in complex tissues, linked with mass fingerprinting and peptide sequencing by Tandem MS/MS for definite characterization

Time-dependent changes in pulmonary surfactant function and composition in acute respiratory distress syndrome due to pneumonia or aspiration

BACKGROUND: Alterations to pulmonary surfactant composition have been encountered in the Acute Respiratory Distress Syndrome (ARDS). However, only few data are available regarding the time-course and duration of surfactant changes in ARDS patients, although this information may largely influence the optimum design of clinical trials addressing surfactant replacement therapy. We therefore examined the time-course of surfactant changes in 15 patients with direct ARDS (pneumonia, aspiration) over the first 8 days after onset of mechanical ventilation. METHODS: Three consecutive bronchoalveolar lavages (BAL) were performed shortly after intubation (T0), and four days (T1) and eight days (T2) after intubation. Fifteen healthy volunteers served as controls. Phospholipid-to-protein ratio in BAL fluids, phospholipid class profiles, phosphatidylcholine (PC) molecular species, surfactant proteins (SP)-A, -B, -C, -D, and relative content and surface tension properties of large surfactant aggregates (LA) were assessed. RESULTS: At T0, a severe and highly significant reduction in SP-A, SP-B and SP-C, the LA fraction, PC and phosphatidylglycerol (PG) percentages, and dipalmitoylation of PC (DPPC) was encountered. Surface activity of the LA fraction was greatly impaired. Over time, significant improvements were encountered especially in view of LA content, DPPC, PG and SP-A, but minimum surface tension of LA was not fully restored (15 mN/m at T2). A highly significant correlation was observed between PaO(2)/FiO(2 )and minimum surface tension (r = -0.83; p < 0.001), SP-C (r = 0.64; p < 0.001), and DPPC (r = 0.59; p = 0.003). Outcome analysis revealed that non-survivors had even more unfavourable surfactant properties as compared to survivors. CONCLUSION: We concluded that a profound impairment of pulmonary surfactant composition and function occurs in the very early stage of the disease and only gradually resolves over time. These observations may explain why former surfactant replacement studies with a short treatment duration failed to improve outcome and may help to establish optimal composition and duration of surfactant administration in future surfactant replacement studies in acute lung injury

Heart rate variability is related to disease severity in children and young adults with pulmonary hypertension

Background: Pulmonary hypertension (PH) is frequently associated with an increase in sympathetic tone. This may adversely affect cardiac autonomic control. Knowledge about the clinical impact of autonomic dysfunction in patients with PH is limited. We aimed to assess whether parameters of heart rate variability (HRV) are related to disease severity in children with PH. Methods: Parameters of HRV [SDNN, standard deviation of normal-to-normal intervals and SDANN, standard deviation of mean values for normal-to-normal intervals over 5 min] were determined from Holter electrocardiograms of 17 patients with PH without active intracardial shunt (10 female, mean age 12.8 ± 8.7 years). Patients were allocated to two groups according to their disease severity: patients with moderate PH [ratio of pulmonary to systemic arterial pressure (PAP/SAP ratio) 0.75) (n = 6). An additional group of five adolescents with Eisenmenger syndrome (PAP/SAP ratio 1.13 ± 0.36) was included. Results: Children with severe PH had significantly lower values of HRV [SDNN (73.8 ± 21.1 vs. 164.9 ± 38.1 ms), SDANN (62.2 ± 19.0 vs. 139.5 ± 33.3 ms)] compared to patients with moderate PH (p = 0.0001 for all). SDNN inversely correlated with ratio of PAP/SAP of PH patients without shunt (r = -0.82; p = 0.0002). Eisenmenger patients showed no significant difference of HRV [SDNN 157.6 ± 43.2 ms, SDANN 141.2 ± 45.3 ms] compared to patients with moderate PH without shunt (p > 0.05 for all). Conclusion: According to our results, children with severe PH may have alterations in HRV. Since HRV appears to be related to disease severity, it may therefore serve as an additional diagnostic marker of PH. Remarkably, although Eisenmenger patients have systemic pulmonary arterial pressures, they seem to have preserved HRV, which might reflect a more favorable autonomic adaptation