Efficacy of recombinant human granulocyte colony stimulating factor in very-low-birth-weight infants with early neutropenia

Background/PurposeNeutropenia is a risk factor for nosocomial infections (NI) in very-low-birth-weight (VLBW) infants. Although recombinant human granulocyte colony stimulating factor (rhG-CSF) increases the neutrophil counts in neutropenic VLBW infants, its long-term efficacy for early neutropenia (EN) remains unknown.MethodsIn this case-controlled study, charts of VLBW recipients of rhG-CSF for EN (total neutrophil count <1.5 × 109/L during first 7 days) were reviewed and compared to gestational age, total neutrophil count, and birth weight matched infants unexposed to rhG-CSF.ResultsTwenty-seven infants were identified in each group. Mortality and morbidity did not differ between the two groups. Rate of NI (16/27 vs. 4/27, p = 0.002, odds ratio = 8.36) as well as the total number of episodes of NI (22 vs. 4, p = 0.007) were higher in rhG-CSF (+) group than in the rhG-CSF (–) group.ConclusionOur experience does not show benefit in empirical use of rhG-CSF in preventing NI in VLBW infants with EN

The Protein Partners of GTP Cyclohydrolase I in Rat Organs

GTP cyclohydrolase I (GCH1) is the rate-limiting enzyme for tetrahydrobiopterin biosynthesis and has been shown to be a promising therapeutic target in ischemic heart disease, hypertension, atherosclerosis and diabetes. The endogenous GCH1-interacting partners have not been identified. Here, we determined endogenous GCH1-interacting proteins in rat.A pulldown and proteomics approach were used to identify GCH1 interacting proteins in rat liver, brain, heart and kidney. We demonstrated that GCH1 interacts with at least 17 proteins including GTP cyclohydrolase I feedback regulatory protein (GFRP) in rat liver by affinity purification followed by proteomics and validated six protein partners in liver, brain, heart and kidney by immunoblotting. GCH1 interacts with GFRP and very long-chain specific acyl-CoA dehydrogenase in the liver, tubulin beta-2A chain in the liver and brain, DnaJ homolog subfamily A member 1 and fatty aldehyde dehydrogenase in the liver, heart and kidney and eukaryotic translation initiation factor 3 subunit I (EIF3I) in all organs tested. Furthermore, GCH1 associates with mitochondrial proteins and GCH1 itself locates in mitochondria.GCH1 interacts with proteins in an organ dependant manner and EIF3I might be a general regulator of GCH1. Our finding indicates GCH1 might have broader functions beyond tetrahydrobiopterin biosynthesis

Nogo-B Receptor (NgBR): A New Receptor that Modulates Blood Vessel Formation

Nogo-B is an isoform of reticulon-4 (RTN4) that distributes mainly in the endoplasmic reticulum. Nogo-B binds to its receptor, Nogo-B receptor (NgBR), to modulate blood vessel formation. Animal with Nogo-B knockout is phenotypically normal. NgBR is a type I receptor with a single transmembrane domain that binds Nogo-B and probably other angiogenic factors. NgBR knockout in zebra fish leads to abnormal formation of intersomite vessels suggesting NgBR plays a more important role in the Nogo-B/NgBR signaling pathway. It is reported that NgBR plays a role in dolichol biosynthesis, protein N-glycosylation, stabilizes Niemann-Pick type C2 protein, regulates intracellular cholesterol trafficking, controls blood vessel development, and modulates breast cancer progression. However, the research in NgBR remains in its early stage and needs further exploration

Persistent pulmonary hypertension of the newborn

Persistent pulmonary hypertension of the newborn (PPHN) is a severe pulmonary disorder which occurs at a rate of one in every 500 live births. About 10–50% of the victims will die of the problem and 7–20% of the survivors develop long-term impairments such as hearing deficit, chronic lung disease, and intracranial bleed. Most adult survivors show evidence of augmented pulmonary vasoreactivity, suggesting a phenotypical change. Several animal models have been used to study the pathophysiology and help to develop new therapeutic modality for PPHN. The etiology of PPHN can be classified into three groups: (1) abnormally constricted pulmonary vasculature as a result of parenchymal diseases; (2) hypoplastic pulmonary vasculature; and (3) normal parenchyma with remodeled pulmonary vasculature. Impaired vasorelaxation of pulmonary artery and reduced blood vessel density in lungs are two characteristic findings in PPHN. Medical treatment includes sedation, oxygen, mechanical ventilation, vasorelaxants (inhaled nitric oxide, inhaled or intravenous prostacyclin, intravenous prostaglandin E1, magnesium sulfate), and inotropic agents. Phosphodiesterase inhibitors have recently been studied as another therapeutic agent for PPHN. Endothelin-1 (ET-1) inhibitors have been studied in animals and a case of premature infant with PPHN successfully treated with an ET-I inhibitor has been reported in the literature. Surfactants have been reported as an adjunct treatment for PPHN as a complication of meconium aspiration syndrome. Even with the introduction of several new therapeutic modalities there has been no significant change in survival rate. Extracorporeal membrane oxygenator is used when medical treatment fails and the patient is considered to have a recoverable cause of PPHN