Disease Of Newborn Infant Research Articles

Risk of immune-related diseases in childhood after intrapartum antibiotic exposure

Intrapartum antibiotic prophylaxis is effective in preventing early-onset group B streptococcal disease in newborn infants, but it influences gut microbiota development. Gut microbiota composition is, in turn, associated with immune-related diseases in childhood. This study hypothesized that intrapartum antibiotic exposure is associated with immune-related diseases in childhood. We conducted a population-based cohort study of vaginally delivered children. We retrieved data on intrapartum antibiotic exposure from structured electronic medical records and obtained outcome data on childhood autoimmune, allergic, and obstructive airway diseases from comprehensive national registers. We used Cox regression analysis with adjustment for maternal and neonatal covariates and regarded death as a competing risk in the analyses. The study population comprised 45,575 vaginally born children of whom 9733 (21%) had been exposed to intrapartum antibiotics. Intrapartum antibiotic exposure was associated with an autoimmune disease diagnosis (adjusted hazard ratio, 1.28; 95% confidence interval, 1.02-1.62), which corresponds to 22% (95% confidence interval, 6-39) as a theoretical population-attributable fraction. Intrapartum antibiotic exposure was not associated with diagnoses of allergic (adjusted hazard ratio, 1.08; 95% confidence interval, 0.97-1.20) or obstructive airway diseases (adjusted hazard ratio, 1.04; 95% confidence interval, 0.96-1.14). Intrapartum antibiotic exposure may be associated with an increased risk for autoimmune diseases in childhood. This finding supports the efforts to develop more specific group B streptococcal disease prevention strategies in the future.

Need for larger cohorts and standardized tools to study diseases in newborn infants

Need for larger cohorts and standardized tools to study diseases in newborn infants

The specific signs of lung ultrasound to diagnose pulmonary hemorrhage of the newborns: Evidence from a multicenter retrospective case-control study.

Pulmonary hemorrhage (PH) is one kind of critical lung diseases in newborn infants, which is the most difficult one to be diagnosed by ultrasound. This study was to investigate the specific ultrasonic signs of PH in order to better diagnose neonatal PH by using lung ultrasound (LUS). A total 168 newborn infants were enrolled in this study, which included PH, pneumonia, meconium aspiration syndrome, and newborns without lung diseases, there were 42 cases in each group. In a quiet state, infants were placed in the supine, lateral or prone position for the examination. Each lung was divided into the anterior, lateral and posterior regions, then each region of both lungs was scanned with the probe perpendicular to the ribs or parallel to the Intercostal spaces. The major results showed that: (1) the common LUS manifestation of PH includes lung consolidation, air bronchograms, fluid bronchograms, pleural effusion, shred signs, pleural line abnormality and B-lines, while fibrin deposition sign is a rare sign of PH. (2) Co-existing of lung consolidation with fluid bronchograms and pleural effusion is the specific sign of PH with a sensitivity of 81.0%, specificity of 98.4% and the positive predictive value (PPV) was 94.4%. (3) Fibrin deposition sign is an uncommon specific LUS sign of PH with a sensitivity 28.6%, specificity of 100% and the PPV was 100%. (4) Nine patients (21.4%) were diagnosed with PH based on ultrasound findings before oronasal bleeding. (5) The survival rate of infants with PH was 100% in this study. LUS is helpful for the early diagnosis of neonatal PH and may therefore improve the prognosis. The lung consolidation with fluid bronchograms and pleural effusion as well as fibrin deposition sign are specific to diagnose PH by using LUS.

Red blood cell transfusions post diagnosis of necrotizing enterocolitis and the deterioration of necrotizing enterocolitis in full-term and near-term infants: a propensity score adjustment retrospective cohort study

BackgroundNecrotizing enterocolitis (NEC) is one of serious gastrointestinal inflammatory diseases in newborn infants, with a high morbidity and mortality. Red blood cell transfusion (RBCT) plays a controversial and doubtful role in the treatment of NEC. In present study, we aim to analyze the association between RBCT and the deterioration of NEC.MethodsThis was a retrospective cohort study of near-term and full-term infants with a confirmed diagnosis of Bell’s stage II NEC between Jan 1, 2010 and Jan 31, 2020. The maternal and infant baseline characteristics, treatment information and laboratory test for each case were collected. The eligible subjects were divided into two groups based on receiving RBCT post NEC diagnosis or not. The propensity score was used to eliminate potential bias and baseline differences. A multivariate logistic regression model was used to adjust the propensity score and calculate the odds ratio (OR) and 95% confidential interval (CI) of RBCT for the deterioration of NEC.ResultsA total of 242 infants were included in this study, 60 infants had a history of RBCT post NEC diagnosis, and 40 infants deteriorated from Bell’s stage II to stage III. By adjusting the propensity score, RBCT post NEC diagnosis was associated with an increased risk for NEC deteriorating from stage II to III (adjusted OR 6.06, 95%CI 2.94–12.50, P = 0.000).ConclusionsNEC infants who required RBCT post NEC diagnosis were more likely to deteriorate from stage II to III in full-term and near-term infants.

Effects of Neonatal Feeding Patterns on Infant Health.

Objective Early and reasonable feeding mode can not only ensure the good nutritional condition of infants but also enhance the infant immunity and resistance, which has a certain role in promoting health and preventing the occurrence of chronic diseases in adulthood. In this study, the effect of neonatal feeding methods on the infant body, the influence of early feeding on the growth rate, and development of infants aged 0-3. Method From January 2016 to June 2019, a total of 600 infants who have been systematically managed in our hospital since birth were selected. All newborns were 37-40 weeks old, weighing 2350-4100 g, without congenital diseases. They were grouped according to feeding methods. 194 infants were exclusively breastfed, 32.3%; 207 people were artificially fed, 34.5%; 199 people were mixed fed, 33.2%. The Kaup index method was used to judge the nutritional status. Developmental Screening Test for ages 0 to 6 (DST) and Bailey Infant Development Scale (BIDS) were used to rate the intellectual and behavioral development of infants and children. According to the growth and development reference standard of 0 ~ 4-year-old children recommended by who in 2006, the age weight standard deviation score (WAZ), age length (height) standard deviation score (HAZ), and body (long) height-weight standard deviation score (WHZ) were performed, and the statistical analysis was performed with SPSS24.0 software. The height, weight, intelligence, and motor development of infants in the three groups at 1 month, 3 months, 6 months, 12 months, 24 months, and 36 months were analyzed and compared, and the test results were recorded in detail. Result There was no significant difference in 3-month-old WAZ and HAZ among the three groups (P > 0.05). Within 6 months, the WAZ and HAZ values of the pure breastfeeding group and mixed feeding group were higher than those of the artificial feeding group (P < 0.05). From 6 months to 12 months, the WAZ and HAZ values of the artificial feeding group were better than those of artificial feeding group and mixed feeding group (P < 0.05). The scores of MI, DQ, PDI, and MDI in the mixed feeding group within 12-36 months were slightly higher than those in the breastfeeding group and significantly better than those in the artificial feeding group (P < 0.05). The prevalence of the breastfeeding group was 22.2% (43/194) and mixed feeding group was 19.8% (39/199), which was lower than that of the artificial feeding group 57.8% (120/207), P < 0.01. The number of people with normal psychological development was 88.7% (172/194) in the breastfeeding group and 88.9% (177/199) in the mixed feeding group, which was higher than 76.3% (158/207) in the artificial feeding group (P < 0.01). Conclusion When there is little colostrum secretion in the first 2-3 days of delivery, appropriate addition of formula milk can reduce the incidence of diseases in newborn infants. Breast milk is the most perfect natural food. The immune substance in breast milk is an important element for infants to resist diseases. The communication between mother and child is the first condition for the development of infant mental health.

Intestinal Stem Cell Development in the Neonatal Gut: Pathways Regulating Development and Relevance to Necrotizing Enterocolitis.

The intestine is extremely dynamic and the epithelial cells that line the intestine get replaced every 3–5 days by highly proliferative intestinal stem cells (ISCs). The instructions for ISCs to self-renew or to differentiate come as cues from their surrounding microenvironment or their niche. A small number of evolutionarily conserved signaling pathways act as a critical regulator of the stem cells in the adult intestine, and these pathways are well characterized. However, the mechanisms, nutritional, and environmental signals that help establish the stem cell niche in the neonatal intestine are less studied. Deciphering the key signaling pathways that regulate the development and maintenance of the stem cells is particularly important to understanding how the intestine regenerates from necrotizing enterocolitis, a devastating disease in newborn infants characterized by inflammation, tissues necrosis, and stem cell injury. In this review, we piece together current knowledge on morphogenetic and immune pathways that regulate intestinal stem cell in neonates and highlight how the cross talk among these pathways affect tissue regeneration. We further discuss how these key pathways are perturbed in NEC and review the scientific knowledge relating to options for stem cell therapy in NEC gleaned from pre-clinical experimental models of NEC.

Comparison of 2 Ear Molding Systems for Nonsurgical Management of Newborn Auricular Deformities

Congenital auricular deformities are common diseases in newborn infants. We compared the efficacy of 2 ear molding systems in the nonsurgical management of newborn auricular deformities in Chinese infants. A total of 462 newborns with auricular deformities were treated with either the EarWell or the LiangEar ear molding systems. The posttreatment outcome was graded as excellent, fair, and poor. The differences in effectiveness between the 2 ear molding systems and factors that may affect the posttreatment outcome were analyzed. Both ear molding systems showed substantial efficacy in the treatment of newborn auricular deformities. The effective rate was comparable between the EarWell and the LiangEar systems for 4 types of auricular deformities (cryptotia, prominent ear, helical rim abnormality, and cup ear), while the costs for the LiangEar systems were half as much as that for the EarWell systems. Multivariate regression analysis showed that earlier time points at treatment initiation, less severe auricular deformities, treatment duration, and breastfeeding were the most significant predictive factors for a better outcome. Our findings demonstrate that using the EarWell and the LiangEar systems are both optimal nonsurgical approaches for treatment of most newborn auricular deformities.

A Novel Hexavalent Capsular Polysaccharide Conjugate Vaccine (GBS6) for the Prevention of Neonatal Group B Streptococcal Infections by Maternal Immunization.

BackgroundGroup B streptococcus (GBS) causes serious diseases in newborn infants, often resulting in lifelong neurologic impairments or death. Prophylactic vaccination of pregnant women prior to delivery could provide comprehensive protection, as early onset and late-onset disease and maternal complications potentially could be addressed.MethodsCapsular polysaccharide conjugate vaccine GBS6 was designed using surveillance data yielded by whole-genome sequencing of a global collection of recently recovered GBS isolates responsible for invasive neonatal GBS disease. Capsular polysaccharides were isolated, oxidized using sodium periodate, and conjugated to CRM197 by reductive amination in dimethyl sulfoxide. Immune responses in mice and rhesus macaques were measured in a multiplex Luminex immunoglobulin G (IgG) assay and opsonophagocytic activity assays.ResultsThe optimized conjugates were immunogenic, alone and in combination, in mice and rhesus macaques, inducing IgG antibodies that mediated opsonophagocytic killing. Active immunization of murine dams with GBS6 prior to mating resulted in serotype-specific protection of pups from a lethal challenge with GBS. Protection following passive administration of serotype-specific IgG monoclonal antibodies to dams demonstrated conclusively that anticapsular polysaccharide IgG alone is sufficient for protection.ConclusionsThe findings support the ongoing clinical evaluation of maternal GBS6 vaccination as a potential alternative method to prevent GBS disease in infants.

The Accuracy of Self-Screening of Group B Streptococcus in Pregnant Women-A Randomized Crossover Study.

Universal screening of vaginal and rectal group B streptococcus (GBS) carriage in pregnant women is now recommended in many countries to identify at-risk pregnancies and reduce the risk of early-onset GBS disease in newborn infants. This study compared self-screening by pregnant women with screening by health care workers in a largely Chinese population. A randomized crossover study was conducted in Hong Kong. All women attending the GBS screening visit at 35-37 weeks gestation between May and October 2015 were approached for recruitment. Consenting participants underwent both self-screening and screening by health care workers. Group 1 had health care worker screening swabs first, and group 2 had self-screening first. A positive GBS diagnosis was made if either swab was positive. The sensitivity of each approach was calculated by comparison with this gold standard. Acceptance of GBS self-screening and neonatal outcomes was analyzed (Canadian Task Force Classification I). Of the 672 women approached, 428 (63.7%) consented to the study. The prevalence of GBS was 19.7% (83 of 422). Sensitivities of self-screening and screening by health care workers were 61.4% (51 of 83) and 97.6% (81 of 83), respectively (P<0.05). Women who used vaginal pessaries and non-Chinese women had a higher positive concordance rate with health care workers (P<0.05). Neonatal outcomes of GBS-positive mothers were similar in the concordant and discordant groups. The sensitivity of self-screening of GBS in Hong Kong was lower than the sensitivity of screening by health care workers. Cultural difference needs to be considered when implementing self-screening in different populations.

Analysis of soluble factors in conditioned media derived from primary cultures of cirrhotic liver of biliary atresia.

Biliary atresia (BA) is a rare and serious liver disease in newborn infants. Previously, we reported that non-parenchymal cell (NPC) fractions from cirrhotic liver of BA may contain hepatic stem/progenitor cells in primary culture of NPC fractions. In this study, NPC fractions were subjected to primary or passage culture and found that clusters of hepatocyte-like cells appear even without adding hepatocyte growth factor (HGF) to the culture medium, but not in their passage culture used as a control. Based on these findings, conditioned media (CMs) were collected and soluble factors in the CMs were analyzed in order to elucidate the mechanism of the appearance of hepatocyte-like cells or their clusters. A large amount of active HGF consisting of α and β chains was detected in CMs derived from primary culture, but not in CMs from passage culture, as determined by western blot analysis, bone morphogenetic protein (BMP)-4, oncostatin M (OSM), and transforming growth factor (TGF)-β1 were not detected in any of the CMs. The number of hepatocyte-like cells in primary culture tended to decrease following treatment with the HGF receptor c-Met inhibitor, SU11274 in a dose-dependent manner. Furthermore, the clusters of hepatocyte-like cells tended to increase in size and number when freshly isolated NPC fractions were cultured in the presence of 10% of CMs collected after 3-4wk of primary culture. In conclusion, these findings indicate that CMs derived from primary culture of NPC fractions of BA liver contain a large amount of active HGF, which may activate hepatic stem/progenitor cells and promote the appearance of hepatocyte-like cells or their clusters through HGF/c-Met signaling. The present study would lead to cell therapy using the patient's own cells for the treatment of BA.

Advances in the pathogenesis, diagnosis and therapeutics of necrotizing enterocolitis

Necortizing enterocolitis(NEC)is a common neonatal gastrointestinal disease in new-born infants, especially in lower gestational age and lower birth weight groups.While the exact pathogenesis remains unclear, risk factors including prematurity, bacteria colonization, blood transfusion are confirmed.As recently revealed, ultrasonography and bio-markers can facilitate early diagnosis, whereas reasonable use of probiotics, lactoferrin, nitric oxide, amniotic fluids can effectively reduce the incidence of NEC.This paper is a review on pathogenesis and advances in diagnostic and therapeutic approaches of NEC. Key words: Necrotizing enterocolitis; Pathogenesis; Early diagnosis; Therapy

Importance of gut microbiota in health and diseases of new born infants.

The multifarious assortment of microorganisms present in gut of humans is termed as gut microbiota. These include 1,000 species accompanied by approximately 2 million genes in an individual adult. The gut microbiota has multifactorial protective roles against allergic reactions, inflammation, cardiac pathological states and even in the state of malignant carcinogenesis existing in humans. By contrast, adverse alterations in the microbiota result in chronic pathological states, including autoimmune diseases, cancer and circulatory system obstructions. Gut bacteria also maintain sensitivity towards nutritional changes as well as antibiotics. The present review article focused on the importance of gut bacteria in newborn infants with special reference to their protective role in various pediatric pathological states linked with gut bacteria. In addition, the importance of probiotics in relation to gut microbiota are to be discussed.

Nutritional Issues Surrounding Acute Kidney Injury and Chronic Kidney Disease in Newborn Infants

Newborns are more susceptible to renal injury than older infants and children because of the functional and developmental immaturity of the neonatal kidney. Acute kidney injury (AKI) is often transient and part of multiorgan dysfunction especially in premature infants, but could produce long lasting damage to the developing nephrons. The advances in obstetric and neonatal care have improved the survival of the smallest premature infants and infants with renal anomalies-an increasing population at high risk for AKI with the potential for progression to chronic kidney disease (CKD). Nutritional interventions are crucial to therapeutic treatment and optimal outcomes in both AKI and CKD in newborns. Research evidence specific to nutritional management of newborns with AKI/CKD is limited and recommendations often stem from studies in older children with AKI/CKD. This article discusses the nutritional issues surrounding AKI/CKD in infants admitted to the neonatal intensive care unit and recommendations for management based on available evidence to achieve optimal outcomes.

Cathepsin K overexpression modifies lung development in newborn mice

Cathepsin K (CatK), contributes to the development of chronic lung disease in newborn infants, but the impact of CatK for the lungs may be multifaceted. We have previously demonstrated that low level of CatK is associated with newborn lung injury and CatK deficiency aggravates lung injury in hyperoxia-exposed newborn mice. Thus, we hypothesized that sustained/higher expression of CatK could ameliorate hyperoxia-induced injury and restrain the development of pulmonary fibrosis. We studied the lungs of newborn wild-type (WT) and CatK overexpressing transgenic mice (TG) that were exposed to hyperoxia or room air for 7 or 14 days after birth. Fourfold pulmonary overexpression of CatK did not affect the growth or lung weight in room-air bred TG mice. The distal airspaces in TG mice were, however, enlarged on postnatal days (PN) 7 and 14, the latter together with increased apoptosis, compared with WT controls. Survival rate was normal and no respiratory distress was observed in air-bred TG mice. Hyperoxia inhibited alveolarization and increased collagen accumulation in WT mice. In TG mice, hyperoxia for 1 week did not aggravate the lung injury, and the lung morphology and already enlarged alveoli remained unchanged in TG mice at PN7. Prolonged hyperoxic exposure caused significant lung injury and mortality similarly in both group of mice, and only few mice survived until PN14. In summary, CatK overexpression slightly enlarges distal airways in infant mice, but hyperoxic environment is initially better tolerated when compared to WT mice. These findings suggest multifaceted role for CatK in lung development and newborn lung injury.

Incidence and risk factors of parenteral nutrition‐associated liver disease in newborn infants

The aim of the present study was to determine the incidence and risk factors of parenteral nutrition-associated liver disease (PNALD) in neonates. A 1 year prospective cohort study was carried out at the neonatal intensive care unit and sick neonatal wards, Chiang Mai University Hospital. Newborns >1000 g, receiving >7 days of parenteral nutrition (PN), were enrolled. Liver function tests were done by the end of first, second, and fourth week, and then every 4 weeks until the PN was discontinued and the jaundice resolved. The diagnosis of PNALD relied on a history of PN, direct bilirubin >2 mg/dL, and exclusion of other causes of neonatal cholestasis. Selected patient factors and PN compositions were analyzed to determine the risks for development of PNALD. A total of 24 infants with a mean gestational age and birthweight of 32.5 weeks and 1840 g were enrolled. Eight of the 24 developed PNALD. Compared to those without PNALD, gastrointestinal surgery, duration of enteral starvation, duration of PN, maximum PN caloric intake, and maximum carbohydrate intake were significantly associated with the development of liver disease. Despite the lack of statistical significance, there was a trend towards cholestasis in patients with sepsis. Elevation of direct bilirubin was the earliest biochemical change, observed in the first week after PN, followed by increased transaminases. Gastrointestinal surgery, duration of enteral starvation, duration of PN, maximum caloric and carbohydrate intake in PN were significant risks of PNALD in newborn infants.

Clinical and epidemiological features of pyo-inflammatory diseases in the newborns

Aim. To study the clinical and epidemiologic features of pyo-inflammatory diseases in the newborns. Methods. Examined were 60 newborn infants who were admitted to hospital for treatment of pyo-inflammatory diseases in the department of pathology of the newborns of the Republican Clinical Infectious Diseases Hospital. In order to determine the etiology of the disease a bacteriological culture analysis from a variety of epitopes - skin, eyes, navel, nose, throat, intestine was conducted in all children. Results. The vast majority (76.7%) of the infants were born full term and as a result of natural childbirth. The most frequently reported were the infections of the skin and mucous membranes - vesiculo-pustulosis (40%), purulent conjunctivitis (20%) and omphalitis (15%), less frequently - pneumonia (6.7%), pyoderma (5%), felon (5 %) and urinary tract infections (8.3%). In 81.7% of cases the pyo-inflammatory diseases had a moderately severe course. Inflammatory changes in the blood were found only in 26.7% of cases, they manifested by leukocytosis and neutrophilia with varying degrees of severity. The vast majority (81.6%) of cases the disease developed in the first 3 days after birth, indicating either an intranatal or intrauterine mechanism of infection of these newborns. In 42.5% cases the women experienced infectious diseases of the urogenital tract during pregnancy. During microbiological investigation of the external epitopes S. aureus and S. epidermidis were the most frequently seeded strains. Conclusion. The most common pyo-inflammatory diseases in newborn infants, who are hospitalized in an infectious diseases hospital, were diseases of the skin and mucous membranes - vesiculo-pustulosis, purulent conjunctivitis and purulent omphalitis, the development of which occurred in the first 3 days after birth, and the main etiological factors of their emergence were S. aureus and S. epidermidis.

Clinical Impacts of Delayed Diagnosis of Hirschsprung’s Disease in Newborn Infants

Asian infants are at a higher risk of having Hirschsprung's disease (HD). Although HD is surgically correctable, serious and even lethal complications such as Hirschsprung's-associated enterocolitis (HAEC) can still occur. The aim of this study was to investigate the risk factors of HAEC, and the clinical impacts of delayed diagnosis of HD in newborn infants. By review of medical charts in a medical center in Taiwan, 51 cases of neonates with HD between 2002 and 2009 were collected. Patients were divided into two groups based on the time of initial diagnosis: Group I, diagnosis made within 1 week after birth, and Group II after 1 week. Clinical features including demographic distribution, presenting features of HD, short-term and long-term complications related to HD were compared between the two groups of patients. There were 25 patients in Group I and 19 in Group II. Group II patients had more severe clinical signs and symptoms of HAEC than Group I patients. The incidence of preoperative HAEC was 12% in Group I and 63% in Group II (adjusted odds ratio = 12.81, confidence interval = 2.60-62.97). Patients with preoperative HAEC were more likely to develop adhesive bowel obstruction after operation (33% vs. 3%, p = 0.013) and failure to thrive (33% vs. 3%, p = 0.013). Also, patients with long-segment or total colonic aganglionosis were at risk of developing both postoperative HAEC (85% vs. 29%, p = 0.001) and failure to thrive (39% vs. 3%, p = 0.002). In our study, we found that delayed diagnosis of HD beyond 1 week after birth significantly increases the risk of serious complications in neonatal patients. Patients with long-segment or total colonic aganglionosis have higher risk of postoperative HAEC and failure to thrive. Patients with preoperative HAEC are more likely to have adhesive bowel obstruction and failure to thrive.

Neuroprotective effects of NEP1-40 and fasudil on Nogo-A expression in neonatal rats with hypoxic-ischemic brain damage

The hypoxic-ischemic encephalopathy caused by peripartum asphyxia is a serious disease in newborn infants, and effective therapies need to be developed to reduce injury-related disorders. We evaluated the effects of NEP1-40 and fasudil on Nogo-A expression in neonatal hypoxic-ischemic brain damage (HIBD) rats. Seven-day-old Wistar rats were randomly divided into control, HIBD, NEP1-40, and fasudil groups. NEP1-40 and fasudil groups were injected intraperitoneally with these compounds. Rat brains at 6, 24, 72 h, and 7 days after HIBD were collected to determine histopathological damage and the expression levels of Nogo-A. Histopathological damage was reduced in NEP1-40 and fasudil groups compared with the untreated HIBD group. The expression of Nogo-A in the HIBD group was significantly higher than that in control, NEP1-40 and fasudil groups at the same times. Compared with the fasudil group, the expression levels of Nogo-A were significantly reduced in the NEP1-40 group. We conclude that NPE1-40 and fasudil have potential for neuroprotective effects in the neonatal rat HIBD model, mediated by inhibiting Nogo-A/ Rho pathways.

Clinical utility of TSH receptor antibody determination

It is generally accepted that antibody to thyrotropin receptor (TRAb) with stimulatory activity is the major pathogenetic factor in Graves' disease. Despite that, determination of these autoantibodies is not a routine analysis in clinical practice. Aim of this paper is analyzing and presenting of some modalities in clinical protocol for diagnosis, differential diagnosis and follow-up of treatment in management of Graves' disease. By these examinations it is possible differentiation between autoimmune and other forms of thyrotoxicosis (autonomous hyperthyroidism, destructive thyroiditis, iodine induced hyperthyroidism etc). Under influence of antithyroid medicaments elevated TRAb decrease and become negative in real (immune) remission. If TRAb stay positive patients are candidates for relapse - prediction of therapeutic response. Follow-up of TRAb in pregnant women is important predictive sign for expected thyroid immune disease in newborn infants. In our opinion, confirmed by presented results, application of TRAb determination in many clinical situations is justified.

Extracellular High Mobility Group Box-1 (HMGB1) Inhibits Enterocyte Migration via Activation of Toll-like Receptor-4 and Increased Cell-Matrix Adhesiveness

Toll-like receptor-4 (TLR4) is the receptor for bacterial lipopolysaccharide, yet it may also respond to a variety of endogenous molecules. Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in newborn infants and is characterized by intestinal mucosal destruction and impaired enterocyte migration due to increased TLR4 signaling on enterocytes. The endogenous ligands for TLR4 that lead to impaired enterocyte migration remain unknown. High mobility group box-1 (HMGB1) is a DNA-binding protein that is released from injured cells during inflammation. We thus hypothesize that extracellular HMGB1 inhibits enterocyte migration via activation of TLR4 and sought to define the pathways involved. We now demonstrate that murine and human NEC are associated with increased intestinal HMGB1 expression, that serum HMGB1 is increased in murine NEC, and that HMGB1 inhibits enterocyte migration in vitro and in vivo in a TLR4-dependent manner. This finding was unique to enterocytes as HMGB1 enhanced migration of inflammatory cells in vitro and in vivo. In seeking to understand the mechanisms involved, TLR4-dependent HMGB1 signaling increased RhoA activation in enterocytes, increased phosphorylation of focal adhesion kinase, and increased phosphorylation of cofilin, resulting in increased stress fibers and focal adhesions. Using single cell force traction microscopy, the net effect of HMGB1 signaling was a TLR4-dependent increase in cell force adhesion, accounting for the impaired enterocyte migration. These findings demonstrate a novel pathway by which TLR4 activation by HMGB1 delays mucosal repair and suggest a novel potential therapeutic target in the amelioration of intestinal inflammatory diseases like NEC.