Cooling Effect on Skin Microcirculation in Asphyxiated Newborn Infants with Increased C-Reactive Protein.

BACKGROUND: Therapeutic hypothermia is presumed to suppress inflammatory processes after perinatal asphyxia. In a previous study of neonatal hypoxic-ischemic encephalopathy (HIE) we found altered skin microcirculation in about a third of the infants after rewarming. We speculated whether this could be linked to increased inflammatory responses, such as high C-reactive protein (CRP). The present study further explored this question. OBJECTIVE: The aim of this study was to explore the differences in skin microcirculation and its oxygen delivery ability during cooling and after rewarming in HIE infants with or without high CRP. METHODS: A previously studied population of 28 HIE infants was divided into two subgroups depending on low or high CRP (repeated values above 30 mg/l for more than 24 h). The differences between the two groups regarding laser Doppler perfusion measurements (LDPMs), computer-assisted video microscopy and diffuse reflectance spectroscopies during cooling on days 1 and 3 and after rewarming on day 4 were assessed. RESULTS: After rewarming, infants with high CRP showed significantly higher skin LDPM perfusion, lower functional vessel density and larger heterogeneity of capillary flow velocities as compared to infants with low CRP, while no such differences were found during cooling. CONCLUSION: Skin microcirculatory responses differed significantly after rewarming, but not during cooling, between asphyxiated neonates with or without high CRP. We speculate whether cooling influences the inflammatory skin microcirculatory response and the ability of oxygen delivery to the cells. Further studies are needed to investigate this as well as its applicability to other vascular beds in the body.

Noninvasive assessments of oxygen delivery from the microcirculation to skin in hypothermia-treated asphyxiated newborn infants.

BACKGROUND: Therapeutic hypothermia (TH) has become standard treatment for severe and moderate hypoxic-ischemic neonatal encephalopathy (HIE). Our group has developed an optically based, noninvasive concept of assessing the capacity for oxygen delivery from the microcirculation to the cells of a tissue under investigation. The hypothesis was that mechanisms of reduced oxygen delivery due to reduced metabolism in cooled asphyxiated neonates could be characterized with this concept. METHODS: The skin of 28 asphyxiated newborn infants was studied on days 1 and 3 during TH and on day 4 following rewarming with laser Doppler perfusion measurements (LDPM), computer-assisted video microscopy (CAVM), and diffuse reflectance spectroscopy (DRS). Twenty-five healthy neonates served as a control group. RESULTS: The LDPM decreased during cooling (P < 0.01). Functional capillary density was higher both during and following TH compared with control infants (P < 0.01). Capillary flow velocities were reduced during TH (P < 0.05). The heterogeneity of the flow velocities was larger in the HIE infants than in the control infants. Tissue oxygen extraction was higher during TH (P < 0.01). CONCLUSION: This study indicates that assessments of skin microvascular density, capillary flow velocity, and oxygen extraction can be used to characterize reduced oxygen delivery to cells during TH.

Surface display of N-terminally anchored invasin by Lactobacillus plantarum activates NF-κB in monocytes.

The probiotic lactic acid bacterium Lactobacillus plantarum is a potential delivery vehicle for mucosal vaccines because of its generally regarded as safe (GRAS) status and ability to persist at the mucosal surfaces of the human intestine. However, the inherent immunogenicity of vaccine antigens is in many cases insufficient to elicit an efficient immune response, implying that additional adjuvants are needed to enhance the antigen immunogenicity. The goal of the present study was to increase the proinflammatory properties of L. plantarum by expressing a long (D1 to D5 [D1-D5]) and a short (D4-D5) version of the extracellular domain of invasin from the human pathogen Yersinia pseudotuberculosis. To display these proteins on the bacterial surface, four different N-terminal anchoring motifs from L. plantarum were used, comprising two different lipoprotein anchors, a transmembrane signal peptide anchor, and a LysM-type anchor. All these anchors mediated surface display of invasin, and several of the engineered strains were potent activators of NF-κB when interacting with monocytes in cell culture. The most distinct NF-κB responses were obtained with constructs in which the complete invasin extracellular domain was fused to a lipoanchor. The proinflammatory L. plantarum strains constructed here represent promising mucosal delivery vehicles for vaccine antigens.