Endothelin-1 signaling promotes fibrosis in vitro in a bronchopulmonary dysplasia model by activating the extrinsic coagulation cascade.

Neonatal respiratory distress syndrome can progress to bronchopulmonary dysplasia (BPD), a serious pulmonary fibrotic disorder. Given the involvement of the extrinsic coagulation cascade in animal models of lung fibrosis, we examined its role in BPD. We observed a higher number of neutrophils expressing tissue factor (TF) in bronchoalveolar lavage fluid (BALF) from infants with BPD than from those with uncomplicated respiratory distress syndrome together with a parallel decrease in TF and connective tissue growth factor (CTGF) in BALF supernatants during the disease course. The involvement of coagulation in the fibrotic process associated with BPD was further evaluated by treating primary human colonic myofibroblasts with BALF supernatants from infants with BPD. These human colonic myofibroblasts demonstrated an enhanced C5a- and thrombin-dependent migration. Moreover, they expressed TF in an endothelin-1-dependent manner, with subsequent activation of the extrinsic coagulation cascade and CTGF production mediated by protease-activator receptor-1 signaling. These data provide a novel mechanism for the development of BPD and indicate that endothelin-1 signaling contributes to fibrosis by upregulating a TF/thrombin amplification loop responsible for CTGF production, and offer novel and specific therapeutic targets for pulmonary fibrotic disease.

Optimal timing for repair of an inguinal hernia in premature infants.

PURPOSE: The aim of this study was to determine the optimal timing for inguinal herniotomy in premature infants treated in the neonatal intensive care unit. METHODS: A two-institutional-center retrospective study was performed including 41 prematures at gestational age 28-35 weeks who underwent herniotomy within 1 week of diagnosis [short-waiting group (SWG), median 5 days, n = 25] or more than 1 week after diagnosis [long-waiting group (LWG), median 30.55 days, n = 16]. Gestational age, birthweight, post-conceptional age at diagnosis, age at diagnosis, post-conceptional age at surgery, age at surgery, weight at surgery, timing of surgery, operative time, and occurrence of incarceration, postoperative apnea, hernia recurrence, testicular atrophy, and hospital stay were compared between the two groups. Statistical analysis was performed using one-way ANOVA. RESULTS: Twelve preoperative episodes of incarceration occurred: three in the SWG and nine in the LWG (P < 0.05). Six infants had apnea postoperatively: four in the SWG and two in the LWG (P > 0.05). Follow-up revealed five hernia recurrences, one in the SWG and four in the LWG (P < 0.05); four testicular atrophies were found, one in the SWG and three in the LWG (P > 0.05). CONCLUSION: Early elective herniotomy should be considered in prematures in order to avoid perioperative morbidity and to reduce the risk of incarceration and subsequent testicular ischemia, and hernia recurrence.

Social and psychological characteristics of Greek secondary school students with learning difficulties.

In Greece there is an almost total lack of special education after the primary school (6th grade). This is a descriptive study that aimed to examine social, academic and psychological characteristics of secondary school students with a history of special placement during primary school. It compared 86 students with a placement (group A) with their 1284 schoolmates with no such placement history (group B) with respect to scores on School Adjustment Scale, Academic Motivation Self-Rating Inventory and Youth Self-Report. Group A presented more family social, academic and psychological problems such as: One-parent family, lower socioeconomic status, poor adjustment, low motivation and (especially for boys) high internalizing and externalizing scores. The high rates of failure and dropout of these students indicate that in Greece there is a need to set up appropriate services to help secondary school students with learning difficulties.