ABSTRACT
BACKGROUND: Photobiomodulation by 670 nm red light in animal models reduced severity of ROP and improved survival. This pilot randomised controlled trial aimed to provide data on 670 nm red light exposure for prevention of ROP and survival for a larger randomised trial. METHODS: Neonates <30 weeks gestation or <1150 g at birth were randomised to receive 670 nm for 15 min (9 J/cm2) daily until 34 weeks corrected age. DATA COLLECTED: placental pathology, growth, days of respiratory support and oxygen, bronchopulmonary dysplasia, patent ductus arteriosus, necrotising enterocolitis, sepsis, worst stage of ROP, need for laser treatment, and survival. RESULTS: Eighty-six neonates enrolled-45 no red light; 41 red light. There was no difference in severity of ROP (<27 weeks-p = 0.463; ≥27 weeks-p = 0.558) or requirement for laser treatment (<27 weeks-p = 1.00; ≥27 weeks-no laser treatment in either group). Survival in 670 nm red light treatment group was 100% (41/41) vs 89% (40/45) in untreated infants (p = 0.057). CONCLUSION: Randomisation to receive 670 nm red light within 24-48 h after birth is feasible. Although no improvement in ROP or survivability was observed, further testing into the dosage and delivery for this potential therapy are required.
Subject(s)
Low-Level Light Therapy/instrumentation , Retinopathy of Prematurity/prevention & control , Australian Capital Territory , Birth Weight , Female , Gestational Age , Humans , Infant, Extremely Premature , Infant, Low Birth Weight , Infant, Newborn , Low-Level Light Therapy/adverse effects , Male , Pilot Projects , Prospective Studies , Retinopathy of Prematurity/diagnosis , Severity of Illness Index , Time Factors , Treatment OutcomeABSTRACT
Maternal immune dysregulation seems to affect fetal or postnatal immune development. Preeclampsia is a pregnancy-associated disorder with an immune basis and is linked to atopic disorders in offspring. Here we show reduction of fetal thymic size, altered thymic architecture and reduced fetal thymic regulatory T (Treg) cell output in preeclamptic pregnancies, which persists up to 4 years of age in human offspring. In germ-free mice, fetal thymic CD4+ T cell and Treg cell development are compromised, but rescued by maternal supplementation with the intestinal bacterial metabolite short chain fatty acid (SCFA) acetate, which induces upregulation of the autoimmune regulator (AIRE), known to contribute to Treg cell generation. In our human cohorts, low maternal serum acetate is associated with subsequent preeclampsia, and correlates with serum acetate in the fetus. These findings suggest a potential role of acetate in the pathogenesis of preeclampsia and immune development in offspring.
Subject(s)
Acetates/blood , Fetus/immunology , Pre-Eclampsia/immunology , Prenatal Exposure Delayed Effects/immunology , T-Lymphocytes, Regulatory/immunology , Acetates/administration & dosage , Acetates/immunology , Acetates/metabolism , Adult , Animals , Animals, Newborn , Case-Control Studies , Child Development , Child, Preschool , Dietary Supplements , Female , Fetus/cytology , Fetus/diagnostic imaging , Gastrointestinal Microbiome/immunology , Germ-Free Life/immunology , Humans , Immune Tolerance/immunology , Infant , Infant, Newborn , Longitudinal Studies , Maternal-Fetal Exchange/immunology , Mice , Organ Size/immunology , Pre-Eclampsia/blood , Pre-Eclampsia/diagnosis , Pregnancy , Prenatal Exposure Delayed Effects/pathology , Prenatal Exposure Delayed Effects/prevention & control , Prospective Studies , Thymus Gland/cytology , Thymus Gland/diagnostic imaging , Thymus Gland/growth & development , Thymus Gland/immunology , Transcription Factors/immunology , Transcription Factors/metabolism , Ultrasonography, Prenatal , Young Adult , AIRE ProteinABSTRACT
BACKGROUND AND AIMS: The non-steroidal anti-inflammatory drug sulindac is an effective chemopreventive agent in sporadic colorectal cancer but its potential benefit in mismatch repair deficient cancers remains to be defined. We wanted to determine whether genetic defects that are relevant for colorectal cancer, such as Msh2 or p53 deficiency, would influence the efficiency of sulindac chemoprevention or increase the side effects. METHODS: Msh2 or p53 deficient and wild-type mice received feed containing 160-320 ppm sulindac for up to 25 weeks with or without a concurrent treatment with the carcinogen azoxymethane. Colon tissue was analysed by histopathology and molecular biology methods. RESULTS: We show that sulindac prevented azoxymethane-induced distal colon tumours in all mice. In the proximal colon, however, sulindac induced new inflammatory lesions on the mucosal folds, which further developed into adenocarcinoma in up to 18-25% of the p53 or Msh2 deficient mice but rarely in wild-type mice. This region in the proximal colon was characterised by a distinct profile of pro- and anti-inflammatory factors, which were modulated by the sulindac diet, including upregulation of hypoxia inducible factor 1α and macrophage inflammatory protein 2. CONCLUSIONS: These data show that the sulindac diet promotes carcinogenesis in the mouse proximal colon possibly through chronic inflammation. Sulindac has both beneficial and harmful effects in vivo, which are associated with different microenvironments within the colon of experimental mice. Deficiency for the Msh2 or p53 tumour suppressor genes increases the harmful side effects of long-term sulindac treatment in the mouse colon.