TRANSIENT LIPOPOLYSACCHARIDE-INDUCED CYTOKINE RESPONSES IN THE MATERNAL AND FETAL GUINEA PIG

The aim of this study was to further investigate the role of pro-inflammatory cytokines in the pathogenesis of fetal cererbral white matter injury associated with chorioamnionitis by charaterizing the time course of the cytokine response in the pregnant guinea pig following a maternal inflammatory insult. Chorioamnionitis increases the risk for fetal brain injury. In the guinea pig, a threshold maternal inflammatory response must be reached for significant fetal brain injury to occur. However, a previous study demonstrated that, by seven days after an acute maternal inflammatory insult, cytokine levels in both maternal and fetal compartments are not different from controls. The purpose of this study, therefore, was to test the hypothesis that a significant cytokine response occurs within the first seven days following an acute maternal inflammatory response. Pregnant guinea pigs (n=34) were injected intraperitoneally with 100µg/kg lipopolysaccharide (LPS) at 70% gestation and euthanized at 24 hours, 48 hours or 5 days following endotoxin exposure. Control animals were euthanized at 70% gestation without exposure. Concentrations of interleukin-6, interleukin 1-β and tumour necrosis factor-α (IL-6, IL-1β, TNF-α) were quantified in the maternal serum and amniotic fluid by enzyme-linked immunosorbent assay. IL-6 and IL-1β concentrations were elevated in the maternal serum at 24 hours and returned to control levels by five days. In the amniotic fluid, IL-6 peaked at 48 hours and IL-1β at 24 hours. TNF-α levels were not significantly increased. A single maternal LPS injection produces transient increases in cytokine concentrations in the maternal serum and amniotic fluid. This further implicates the cytokines as potential mediators of fetal white matter damage. Although this response might not be sufficient to produce the brain injury itself, it may initiate harmful pro-inflammatory cytokine cascades, which could even continue to harm the fetus following delivery. A human diagnostic protocol was developed to assess the use of serial serum biomarkers, including IL-6 and TNF-α, in the prediction of histological chorioamnionitis. Preliminary analysis of the pilot study suggests that certain biomarkers might be worthy of further investigation in a larger-scale study.

COGNITIVE ASSESSMENT USING THE KINARM EXOSKELETON ROBOT IN PATIENTS WITH TRANSIENT ISCHEMIC ATTACK

Background: Transient ischemic attack (TIA) is a condition causing focal neurological deficits lasting less than 24hrs. TIA patients present similarly to other conditions with rapid onset of neurological symptoms such as migraine. The accurate diagnosis of TIA is critical because it serves as a warning for subsequent stroke. Furthermore, cognitive deficit associated with TIA may predict the development of dementia. Therefore, characterizing the cognitive symptoms of TIA patients and discriminating these patients from those with similar symptoms is important for proper diagnosis and treatment. Currently the diagnosis of TIA is made on clinical and radiographic evidence. Robotic assessment, with instruments such as the KINARM, may improve the identification of cognitive impairment in TIA patients. Methods: In this prospective cohort study, two KINARM tests, trail making task (TMT) and spatial span task (SST), were used to detect cognitive deficits. Two study groups were made. The TIA group was tested at 5 time points over the span of a year. The migraine active control group had one initial visit and another a year later. Both of these groups were compared to a normative database of approximately 400 healthy volunteers. From this database age and sex matched normative data was used to calculate Z-scores for the TMT. The Montreal Cognitive Assessment (MoCA) was also administered to both groups. Results: 31 participants were recruited, 20 TIA group and 11 active controls (mean ± SD age= 66 ± 11.3 and 62 ± 14.5). There was no significant difference in TIA and active control group MoCA scores. The TMT was able to detect cognitive impairment in TIA and migraine group. Also, both KINARM tasks could detect significant differences in performance between TIA and migraine patients while the MoCA could not. Changes in TIA and migraine performance on the MoCA, TMT, and SST were observed. Conclusions: The robotic KINARM exoskeleton can be used to assess cognitive deficits in TIA patients.

Absolute Absorption Cross-Section Measurement of a Submonolayer film on a silica microresonator

Conventional absorption spectroscopy is not nearly sensitive enough for quantitative overtone measurements on submonolayer coatings. While cavity-enhanced absorption detection methods using microresonators have the potential to provide quantitative absorption cross sections of even weakly absorbing submonolayer films, this potential has not yet been fully realized. To determine the absorption cross section of a submonolayer film of ethylene diamine (EDA) on a silica microsphere resonator, we use phase-shift cavity ringdown spectroscopy simultaneously on near-IR radiation that is Rayleigh backscattered from the microsphere and transmitted through the coupling fiber taper. We then independently determine both the coupling coefficient and the optical loss within the resonator. Together with a coincident measurement of the wavelength frequency shift, an absolute overtone absorption cross section of adsorbed EDA, at submonolayer coverage, was obtained and was compared to the bulk value. The smallest quantifiable absorption cross section is σmin 2.7 × 10−12 cm2. This absorption cross section is comparable to the extinction coefficients of, e.g., single gold nanoparticles or aerosol particles. We therefore propose that the present method is also a viable route to absolute extinction measurements of single particles.

Absorption Measurements in Liquid Core Waveguides Using Cavity

Short liquid core waveguides (LCWs) were included into a fiber-loop cavity ring-down absorption spectrometer to reduce the detection limit over, both, single pass absorption in a LCW and cavityenhanced absorption using a conventional fiber-loop cavity. LCWs of 5 and 10 cm length were interfaced with a pressure-flow system and a multimode fiber-loop cavity using concave fiber lenses with matching numerical apertures and diameters. Two red dyes, Allura Red AC and Congo Red, were detected with a 532 nm pulsed laser at a 5 nM limit of detection in a detection volume of less than 1 μL, corresponding to a minimal detectable absorbance of less than 4 × 10−4 cm−1 and a minimal detectable change in absorption cross section, σmin = Vdet × ε × CLOD, of about 14 μm2 (Allura Red AC) and 37 μm2 (Congo Red).

Absorption Detection Using Optical Waveguide Cavities

Cavity ring-down spectroscopy is a spectroscopic method that uses a high quality optical cavity to amplify the optical loss due to the light absorption by a sample. In this presentation we highlight two applications of phase-shift cavity ring-down spectroscopy that are suited for absorption measurements in the condensed phase and make use of waveguide cavities. In the first application, a fiber loop is used as an optical cavity and the sample is introduced in a gap in the loop to allow absorption measurements of nanoliters of solution at the micromolar level. A second application involves silica microspheres as high finesse cavities. Information on the refractive index and absorption of a thin film of ethylene diamine on the surface of the microresonator is obtained simultaneously by the measurements of the wavelength shift of the cavity mode spectrum and the change in optical decay time, respectively.

Ring-Down Absorption Spectroscopy for Analytical Microdevices

Ring-down absorption spectroscopy is an emerging ‘‘label-free’’ detection method for analytical microdevices, such as micrototal analysis systems (l-TAS). Developed from the related gas-phase cavity ring-down absorption spectroscopy, fiber-optic-based ring-down techniques for liquid samples offer low detection limits, high sensitivity and fast response. ª 2006 Elsevier Ltd. All rights reserved.