Poractant alfa (Curosurf®) increases phagocytosis of apoptotic neutrophils by alveolar macrophages in vivo

<p>Abstract</p> <p>Background</p> <p>Clearance of apoptotic neutrophils in the lung is an essential process to limit inflammation, since they could become a pro-inflammatory stimulus themselves. The clearance is partially mediated by alveolar macrophages, which phagocytose these apoptotic cells. The phagocytosis of apoptotic immune cells by monocytes in vitro has been shown to be augmented by several constituents of pulmonary surfactant, e.g. phospholipids and hydrophobic surfactant proteins. In this study, we assessed the influence of exogenous poractant alfa (Curosurf^®) instillation on the in vivo phagocytosis of apoptotic neutrophils by alveolar macrophages.</p> <p>Methods</p> <p>Poractant alfa (200 mg/kg) was instilled intratracheally in the lungs of three months old adult male C57/Black 6 mice, followed by apoptotic neutrophil instillation. Bronchoalveloar lavage was performed and alveolar macrophages and neutrophils were counted. Phagocytosis of apoptotic neutrophils was quantified by determining the number of apoptotic neutrophils per alveolar macrophages.</p> <p>Results</p> <p>Exogenous surfactant increased the number of alveolar macrophages engulfing apoptotic neutrophils 2.6 fold. The phagocytosis of apoptotic neutrophils was increased in the presence of exogenous surfactant by a 4.7 fold increase in phagocytosed apoptotic neutrophils per alveolar macrophage.</p> <p>Conclusions</p> <p>We conclude that the anti-inflammatory properties of surfactant therapy may be mediated in part by increased numbers of alveolar macrophages and increased phagocytosis of apoptotic neutrophils by alveolar macrophages.</p

Modulation of the adenosine-bound vascular response of the rat kidney by inhibition of the cyclooxygenasis and the NO-synthasis

In der vorliegenden Arbeit wurde an narkotisierten Ratten die hämodynamische Antwort der Niere auf Einzelinjektionen von Adenosin in die Arteria abdominalis oberhalb des Abgangs der Nierenarterie mit einem elektromagnetischen Flußmessgerät untersucht. Der Einfluß der Verminderung des renalen Perfusionsdrucks auf die Adenosin-bedingte Vasokonstriktion wurde quantifiziert. Zusätzlich wurde die Wirkung eines Cyclooxygenase (COX) Hemmstoffes, Indomethacin und eines Hemmstoffes der NO-Synthase (NOS), L-Nitroarginin, auf die vaskuläre Antwort der Niere erfaßt. Die Ergebnisse lassen sich wie folgt zusammenfassen: 1. Der renale Blutfluß fällt kurzfristig und dosisabhängig nach intraarterieller Einzelinjekiton von Adenosin (0,01–100 nmol) ab. 2. Die Verminderung des renalen Perfusionsdrucks auf 65–70 mmHg schwächte die vasokonstriktive Potenz von Adenosin ab. 3. Der COX-Inhibitor Indomethacin verschob die Dosis-Wirkungs-Kurve zwischen Adenosin und renalem Blutfluß sowohl unter Kontrollbedingungen als auch bei reduziertem renalem Perfusionsdruck nach links. 4. Der kompetitive Hemmstoff der NOS, L-Nitroarginin steigerte ebenfalls die vasokonstriktive Wirkung von Adenosin. Das Ausmaß der Linksverschiebung war dem des Indomethacin ähnlich. 5. Die Potenzierung der Adenosin-bedingten renalen Vasokonstriktion durch Hemmungstoffe der Cyclooxygenase und der NO-Synthase hat auch eine klinische Bedeutung, denn COX-Inhibitoren und der Mangel an NO-Bildung (“endotheliale Dysfunktion“) sind mit einem signifikant erhöhten Risiko für die Entwicklung eines akuten Nierenveragens verbunden. So führt dieser klinische Bezug der vorliegenden Ergebnisse zu der Empfehlung, Adenosin-Antagonisten, wie Theophyllin zur Verbesserung der geschädigten Nierenfunktion in klinischen Studien und zur Therapie des ANV einzusetzen.In this study the vascular reaction of the rat kidney to adenosine single injections and the modulation of the vascular reaction were observed. The rats were narcotised with Thiobutabarbital and after preparation the flow of the renal artery was measured by electromagnetic flow probe. The influence of a reduced renal perfusion pressure to the vascular response to adenosine was quantified. In a second step the response to adenosine was modulated by inhibiting of the cyclooxygenasis (COX) by indomethacin or the NO-synthasis (NOS) by L-Nitroarginin. The following results show, that: 1. The reduction of the renal blood flow is of short duration and dependant of the adenosine dose (0,01–100 nmol). 2. The reduction of the renal perfusion pressure to 65–70 mmHg decreased the vascular reaction to adenosine. 3. The inhibition of the COX increased the vascular reactivity to adenosine incetions as well with normal renal perfusion pressure as with reduced renal perfusion pressure. 4. The competitive inhibition of the NO-synthasis increased the vascular response to adenosine in the same range compared to the inhibition of the cyclooxygenasis. 5. NO-deficiency (“endothelial dysfunction“) and abuse of COX-inhibiting drugs is seen for a significant increased risk for an acute renal failure. The potency of the adenosine bound renal vasoconstriction by inhibition of the cyclooxygenasis and the NO-synthasis may be a model for this increased risk for an acute renal failure, so that the clinical connotation of the results recommend adenosine-antagonists for clinical studies of the prevention and treatment of the acute renal failure

Research briefings: the 'Effects of transfusion thresholds on neurocognitive outcome of extremely low birth-weight infants (ETTNO)' study: background, aims, and study protocol

Background: Infants with extremely low birth weight uniformly develop anemia of prematurity and frequently require red blood cell transfusions (RBCTs). Although RBCT is widely practiced, the indications remain controversial in the absence of conclusive data on the long-term effects of RBCT. Objectives: To summarize the current equipoise and to outline the study protocol of the 'Effects of Transfusion Thresholds on Neurocognitive Outcome of extremely low birth-weight infants (ETTNO)' study. Methods: Review of the literature and design of a large pragmatic randomized controlled trial of restrictive versus liberal RBCT guidelines enrolling 920 infants with birth weights of 400-999 g with long-term neurodevelopmental follow-up. Results and Conclusions: The results of ETTNO will provide definite data about the efficacy and safety of restrictive versus liberal RBCT guidelines in very preterm infants