Intestinal epithelia are critical for maintaining gastrointestinal homeostasis. Epithelial barrier injury, causing inflammation and vascular damage, results in inflammatory hypoxia, and thus, healing ...occurs in an oxygen-restricted environment. The transcription factor hypoxia-inducible factor (HIF)-1 regulates genes important for cell survival and repair, including the cell adhesion protein β1-integrin. Integrins function as αβ-dimers, and α-integrin-matrix binding is critical for cell migration. We hypothesized that HIF-1 stabilization accelerates epithelial migration through integrin-dependent pathways. We aimed to examine functional and posttranslational activity of α-integrins during HIF-1-mediated intestinal epithelial healing. Wound healing was assessed in T84 monolayers over 24 h with/without prolyl-hydroxylase inhibitor (PHDi) (GB-004), which stabilizes HIF-1. Gene and protein expression were measured by RT-PCR and immunoblot, and α-integrin localization was assessed by immunofluorescence. α-integrin function was assessed by antibody-mediated blockade, and integrin α6 regulation was determined by HIF-1α chromatin immunoprecipitation. Models of mucosal wounding and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis were used to examine integrin expression and localization in vivo. PHDi treatment accelerated wound closure and migration within 12 h, associated with increased integrin α2 and α6 protein, but not α3. Functional blockade of integrins α2 and α6 inhibited PHDi-mediated accelerated wound closure. HIF-1 bound directly to the integrin α6 promoter. PHDi treatment accelerated mucosal healing, which was associated with increased α6 immunohistochemical staining in wound-associated epithelium and wound-adjacent tissue. PHDi treatment increased α6 protein levels in colonocytes of TNBS mice and induced α6 staining in regenerating crypts and reepithelialized inflammatory lesions. Together, these data demonstrate a role for HIF-1 in regulating both integrin α2 and α6 responses during intestinal epithelial healing.
HIF-1 plays an important role in epithelial restitution, selectively inducing integrins α6 and α2 to promote migration and proliferation, respectively. HIF-stabilizing prolyl-hydroxylase inhibitors accelerate intestinal mucosal healing by inducing epithelial integrin expression.
Male Fischer-344 rats were exposed by inhalation to 1200 ppm toluene (14 hr/day, 7 days/week for 5 weeks) beginning just after weaning or as young adults. During the fifth week of exposure, they were ...trained to perform a multisensory conditioned pole-climb avoidance response (CAR) task using a 4-kHz tone, a change in the intensity of the test chamber light, or a nonaversive current on the grill floor as the stimuli. When tested the week after the exposures ended, both groups of toluene-exposed rats were deficient in their performance of the CAR to a 20-kHz tone. This effect was significantly greater for the rats exposed beginning just after weaning than it was for the young adult rats. Subsequent behavioral and electrophysiologic audiometry confirmed the presence of a toluene-induced high-frequency hearing loss in both groups of rats with the more severe deficits occurring in the younger rats. Preliminary morphologic examinations revealed loss of, and/or damage to, hair cells in the basal turn of the cochlea of the younger toluene-exposed rats. These results confirm our earlier discovery that inhalation exposure to toluene causes hearing deficits in rats, and they indicate that young, prepubertal rats are more severely affected than older rats.
Sampling distortion product otoacoustic emissions (DPOAEs) at multiple f
2
/f
1
ratios and f
2
frequency values produces a DPOAE "map." This study examined the efficacy of DPOAE mapping compared with ...pure tone audiometry and standard DPOAEs for detecting noise effects in subjects exposed to loud sound.
A map significance score was developed as a single measure of map change. Significance scores were evaluated before and after exposure to: loud music (LM), controlled noise (CN), and firing range noise (FR) in three separate sets of subjects. Scores were compared to audiometry and standard DPOAE results in the LM study.
The LM and CN exposure studies involved 22, and 20 healthy young subjects respectively with normal hearing. Eight Marines were studied before and after FR exposure.
After LM exposure, audiometry showed significant changes at 1, 2, 4, and 6 kHz. Standard DPOAE measures were also significantly different at several frequencies. Map significance scores detected changes more effectively and showed the distribution of DPOAE alterations.
Map significance scores detected changes after noise exposure more reliably than audiometry and standard DPOAEs. Additionally, maps showed a diffuse response to sound exposure perhaps explaining why individual DP-grams appear less sensitive.
The potential beneficial effects of physical activity during pregnancy on postpartum depressive symptoms (PPD) remain inconclusive. Using data from two prospective French birth cohorts, we aimed to ...examine the relationship between domain-specific physical activity (including leisure-time sedentary behavior) in pregnancy and the occurrence of PPD. Participants of the ELFE cohort (n = 15,538) completed the Pregnancy Physical Activity Questionnaire (PPAQ), which assesses the following physical activity/sedentary behavior domains: household/caregiving, occupational, sports/exercise, transportation and leisure-time sedentary behavior during the third pregnancy trimester. In the EDEN cohort (n = 1745) women completed the Baecke Questionnaire (BQ) measuring occupational, sports/exercise, and leisure-time activity during the first trimester of pregnancy. Depressive symptoms in the first postpartum year were measured using the Edinburgh Postnatal Depression Scale in both cohorts. Associations of physical activity/sedentary behavior with PPD symptoms were determined by logistic regression analysis, with adjustment on potential confounding factors. In the adjusted models, higher levels of household/caregiving activities (OR = 1.10 (95% CI 1.01–1.19)) and leisure-time sedentary behavior (OR = 1.16 (95% CI 1.06–1.23)), in the third pregnancy trimester were associated with an increased odds of PPD. No significant associations were found for physical activity domains during the first pregnancy trimester. Higher levels of household and caregiving activities and leisure-time sedentary behavior in the last trimester of pregnancy appear to increase the likelihood of postpartum depression. Purpose and context should be taken into account when encouraging physical activity as a strategy to help prevent postpartum mental health problems from pregnancy onwards. Reducing sedentary behavior could be a complementary strategy.
•Domain-specific physical activity in pregnancy might impact postpartum depression.•No association between 1st trimester domain-specific physical activity and PPD•Higher levels of Household/caregiving activities in 3rd trimester increased PPD risk•More time spent in sedentary behaviors increased the likelihood of PPD
Background
Lung ultrasound (LUS) is a safe and non-invasive tool that can potentially assess regional lung aeration in newborn infants and reduce the need for X-ray imaging. LUS produces images with ...characteristic artifacts caused by the presence of air in the lung, but it is unknown if LUS can accurately detect changes in lung air volumes after birth. This study compared LUS images with lung volume measurements from high-resolution computed tomography (CT) scans to determine if LUS can accurately provide relative measures of lung aeration.
Methods
Deceased near-term newborn lambs (139 days gestation, term ∼148 days) were intubated and the chest imaged using LUS (bilaterally) and phase contrast x-ray CT scans at increasing static airway pressures (0–50 cmH
2
O). CT scans were analyzed to calculate regional air volumes and correlated with measures from LUS images. These measures included (i) LUS grade; (ii) brightness (mean and coefficient of variation); and (iii) area under the Fourier power spectra within defined frequency ranges.
Results
All LUS image analysis techniques correlated strongly with air volumes measured by CT (
p
< 0.01). When imaging statistics were combined in a multivariate linear regression model, LUS predicted the proportion of air in the underlying lung with moderate accuracy (95% prediction interval ± 22.15%,
r
2
= 0.71).
Conclusion
LUS can provide relative measures of lung aeration after birth in neonatal lambs. Future studies are needed to determine if LUS can also provide a simple means to assess air volumes and individualize aeration strategies for critically ill newborns in real time.
Transformer monitoring using the UHF technique Judd, M.D; Pryor, B.M; Kelly, S.C ...
11th International Symposium on High-Voltage Engineering (ISH 99),
1999
Conference Proceeding, Journal Article
The viability of applying UHF partial discharge monitoring techniques to an in-service oil-filled power transformer is established. Discharges in oil are shown to radiate the high frequency signals ...necessary to allow detection. On-site pulse injection is used to test the operation of a UHF coupler fitted to the transformer. The effects of on-load tap changing operations are also investigated. (4 pages)
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