Publications by authors named "Darrin Chester"

3 Publications

  • Page 1 of 1

CC10 reduces inflammation in meconium aspiration syndrome in newborn piglets.

Pediatr Res 2007 Dec;62(6):684-8

Department of Pediatrics, The CardioPulmonary Research Institute, Winthrop University Hospital, SUNY Stony Brook School of Medicine, Mineola, New York 11501, USA.

Complications from meconium aspiration syndrome (MAS) remain significant despite a variety of therapeutic interventions. Clara cell protein (CC10) is a novel anti-inflammatory agent that can also inhibit phospholipase A2 (PLA2) (an important component of meconium). The present study examined whether administration of recombinant human CC10 (rhCC10) would reduce inflammation and improve lung function in a piglet model of MAS. Following meconium instillation, piglets exhibited significant physiologic dysfunction that improved significantly after surfactant administration. Analysis of tracheal aspirates revealed significant increases in both tumor necrosis factor (TNF) alpha and interleukin (IL)-8 after meconium instillation. rhCC10-treated animals had significantly lower TNF-alpha levels at 24 h (561 +/- 321 versus 1357 +/- 675 pg/mL, p < 0.05) compared with saline controls. There were no differences between rhCC10-treated and untreated groups with respect to other measured physiologic variables or inflammatory markers, including secretory PLA2 activity. Histologic analyses revealed marked inflammatory infiltrates and thickened alveolar walls, but no significant differences among rhCC10 and control animals. Newborn piglets with MAS have significant physiologic dysfunction, marked inflammatory changes and histologic abnormalities, which was partially counteracted by a single dose of exogenous surfactant and rhCC10.
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http://dx.doi.org/10.1203/PDR.0b013e31815a5632DOI Listing
December 2007

Safety and efficacy of intratracheal recombinant human Clara cell protein in a newborn piglet model of acute lung injury.

Pediatr Res 2003 Oct 18;54(4):509-15. Epub 2003 Jun 18.

Cardiopulmonary Research Institute, Winthrop-University Hospital, SUNY Stony Brook School of Medicine, Mineola, New York 11501, USA.

Despite the widespread use of exogenous surfactant, acute and chronic lung injury continues to be a major cause of morbidity in preterm infants. CC10 is a protein produced by Clara cells that inhibits phospholipase A2 and has anti-inflammatory and antifibrotic properties. We studied whether intratracheal (IT) recombinant human Clara cell protein (rhCC10) could safely minimize lung injury in a newborn piglet model of acute lung injury. Twenty-nine newborn piglets were given Survanta and then ventilated for 48 h receiving the following: room air (group 1); 100% O2 (group 2); or 100% O2 and 25, 5, or 1 mg/kg (groups 3, 4, and 5, respectively) of IT rhCC10 (diluted to 2 mL/kg with saline) at time 0. Laboratory studies, oxygen ratios, static pressure-volume curves, bronchoalveolar lavage (for inflammatory markers), and histologic analyses were performed over the 48-h study period. Pulmonary compliance and oxygenation were significantly improved in animals receiving 5 mg/kg IT rhCC10 compared with room air and 100% O2 controls (p < 0.004 and p < 0.05, respectively, ANOVA). Reductions in inflammatory markers were seen in animals receiving rhCC10, although changes did not reach statistical significance. No significant toxicity was noted. rhCC10 appeared safe and improved pulmonary function in this newborn piglet model of hyperoxic lung injury. We speculate that rhCC10 may represent a promising therapy for the prevention of lung injury in preterm infants.
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http://dx.doi.org/10.1203/01.PDR.0000081300.49749.87DOI Listing
October 2003

Effects of variable concentrations of inhaled nitric oxide and oxygen on the lungs of newborn piglets.

Pediatr Pulmonol 2002 Jul;34(1):58-65

CardioPulmonary Research Institute, Winthrop-University Hospital, SUNY Stony Brook School of Medicine, Mineola, New York 11501, USA.

We previously demonstrated that inhalation of high concentrations of nitric oxide (iNO) and oxygen for 48 hr causes significant lung injury in newborn piglets. To determine if these effects persist at lower concentrations, groups of newborn piglets were mechanically ventilated for 48 hr with (study 1) constant O(2) (90-100%) and decreasing iNO (100-2 ppm) or (study 2) constant iNO (50 ppm) and decreasing O(2) (95-30%). Bronchoalveolar lavage (BAL) fluid was assayed for surfactant function, and markers of lung inflammation and physiologic parameters were monitored. Neutrophil chemotactic activity (NCA), % neutrophils, and total protein (TP) concentrations decreased significantly in BAL fluid of study 1 piglets as iNO was reduced and inhaled oxygen fraction remained constant, indicating less pulmonary injury at low iNO levels. Low-dose iNO (2 ppm) did not have antiinflammatory effects. However, surfactant function was minimally affected by lowering iNO, and was abnormal in all groups. In contrast, in study 2, pulmonary inflammation and injury were lower when O(2) was decreased to 70% or less, with iNO constant at 50 ppm. Surfactant function normalized and oxygenation improved in study 2 piglets when the inhaled oxygen fraction was decreased and iNO remained constant. These data suggest that iNO- and O(2)-induced lung injury may be minimized by weaning O(2) or iNO, although better physiologic function may be obtained when iNO concentrations are constant and O(2) is reduced. This has important implications in the clinical management of critically ill newborns treated with O(2) and iNO for pulmonary disorders.
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http://dx.doi.org/10.1002/ppul.10128DOI Listing
July 2002