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Surfactant `fortification` by topical inhibition of nuclear factor-kappaB activity
In acute respiratory distress syndrome of term newborn infants, surfactant replacement may be effective because endogenous surfactant is decreased and structurally changed. Inflammation is central to acute respiratory distress syndrome, and hence, attenuation of proinflammatory transcription factor nuclear factor (NF)-kappaB activation in the lung might prevent secondary loss of surfactant function. Can topical inhibition of the nuclear factor solve this life-threatening problem? A brandnew study in cooperation with the research laboratory of a university children`s hospital could offer new treatment option in the future.

In this prospective, randomized, controlled study, we tested the hypothesis that the topical use of a NF-kappaB inhibitor (IkappaB kinase-NF-kappaB essential modulator binding domain [IKK-NBD] peptide), together with surfactant as a carrier substance, improves surfactant function by attenuation of pulmonary inflammation during 24 hrs of mechanical ventilation in a neonatal piglet model of acute respiratory distress syndrome by repeated airway lavage.

SUBJECTS:: A total of 24 anesthetized, mechanically ventilated newborn piglets.

INTERVENTIONS:: After 20 +/- 6 (mean +/- sd) lavages to induce lung failure and inflammation, a porcine surfactant (100 mg/kg) with (S+IKK) or without (S) 1.25 mg of IKK-NBD peptide, or an air bolus (control) was administered into the airways. Lung function was monitored throughout 24 hrs of mechanical ventilation and completed by ex vivo analyses.

MEASUREMENTS AND MAIN RESULTS:: Pao2 (S+IKK, 125 +/- 16 mm Hg; S, 105 +/- 33; control, 61 +/- 20), ventilation efficiency index, functional residual capacity, compliance of the respiratory system, and extravascular lung water (S+IKK, 24 +/- 2 mL/kg; S, 30 +/- 7; control, 34 +/- 8) were all significantly improved in S+IKK piglets after 24 hrs.

Decreased leukocyte concentrations in bronchoalveolar lavage (S+IKK, 152 +/- 94 cells/muL; S, 202 +/- 100; control, 276 +/- 57) were observed together with reduced acid sphingomyelinase activity, lowered ceramide concentrations, improved surfactant function (minimum surface tension: S+IKK, 10.8 +/- 6.1 mN/m; S, 13.2 +/- 3.9; control, 20.9 +/- 8.5), and decreased NF-kappaB activation in lung tissue.

CONCLUSION:: Supplementation of exogenous surfactant with a NF-kappaB inhibitor to create a `fortified` surfactant improves gas exchange, lung function, and pulmonary edema during 24 hrs of mechanical ventilation, without a secondary functional relapse.

Inhibition of NF-kappaB suppressed acid sphingomyelinase activity and ceramide generation, indicating a novel proinflammatory link of NF-kappaB.




Source: von Bismarck P, Klemm K, Wistädt CF, Winoto-Morbach S, Uhlig U, Schütze S, Uhlig S, Lachmann B, Krause MF (2007): Surfactant `fortification` by topical inhibition of nuclear factor-kappaB activity in a newborn piglet lavage model. In: Crit Care Med. 2007 Jul 24;Publish Ahead of Print [Epub ahead of print]


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SWINE PRACTICE

Beta hydroxy beta methyl butyrate and the muscle fibre composition in growing pigsmembers
The aim of this recently online published study was to investigate the effects of excess leucine (Leu) vs. its metabolites α‐ketoisocaproate (KIC) and β‐hydroxy‐β‐methyl butyrate (HMB) on Leu metabolism, muscle fibre composition and muscle growth in growing pigs. Thirty‐two pigs with a similar initial weight (9.55 ± 0.19 kg) were fed 1 of 4 diets for 45 days: basal diet, basal diet + 1.25% L‐Leu, basal diet + 1.25% KIC‐Ca, basal diet + 0.62% HMB‐Ca. The results are very promising!

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