Dose-dependent effects of adalimumab in neonatal rats with hypoxia/reoxygenation-induced intestinal damage.

Tumor necrosis factor-alpha (TNF-α) has an important role in hypoxia/reoxygenation (H/R)-induced intestinal damage. It was shown that blocking TNF-α with infliximab has beneficial effects on experimental necrotizing enterocolitis and hypoxic intestinal injury. However, there is no data about the effect of adalimumab on H/R-induced intestinal damage. Therefore, we aimed to determine potential dose-dependent benefits of adalimumab in such damage in neonatal rats. Wistar albino rat pups were assigned to one of the four groups: control group, hypoxia group, low-dose adalimumab (5 mg/kg/day) treated group (LDAT), and high-dose adalimumab (50 mg/kg/day) treated group (HDAT). On the fourth day of the experiment, all rats except for the control group were exposed to H/R followed by euthanasia. Malondialdehyde (MDA), myeloperoxidase (MPO), TNF-α, total antioxidant capacity (TAC), and total oxidant capacity (TOC) were measured in intestinal tissue. TAC and TOC values were used to calculate the oxidative stress index (OSI). Histopathological injury scores (HIS) were also evaluated in the tissue samples. MDA levels were significantly lower in the LDAT and HDAT groups (p < 0.001). TNF-α levels were significantly lower in the LDAT group (p < 0.001). OSI was significantly higher in the H/R group than in the control and LDAT groups (p < 0.001). Mean HIS values in the LDAT group were significantly lower than those in the H/R and HDAT groups (p < 0.001). This experimental study showed that low-dose adalimumab appears to have a beneficial effect on intestinal injury induced with H/R in neonatal rats.

The effects of bosentan on hyperoxia-induced lung injury in neonatal rats.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains an important cause of morbidity and mortality in premature infants. There is currently no proven effective treatment modality for BPD, and inflammation and oxidative injury play an important role in the pathogenesis of this disease. This study investigated the histopathological and biochemical effects of bosentan, which is a non-specific endothelin receptor antagonist with known antioxidant and anti-inflammatory properties, on hyperoxia-induced lung injury (HILI) in neonatal rats. METHODS: The experiment was performed on newborn rats from the 3rd to the 13th postnatal day. The rats were randomly divided into six groups: Group 1 (air-exposed + saline, n = 6); Group 2 (HILI, n = 8); Group 3 (air-exposed + bosentan, n = 7); Group 4 (HILI + saline, n = 7); Group 5 (HILI + early bosentan-treated group, n = 6), and Group 6 (HILI + late bosentan-treated group, n = 7). Bosentan was administered (30 mg/kg/day) intraperitoneally. The histopathological effects of bosentan on lung tissue were assessed by their alveolar surface area, fibrosis, and smooth muscle actin (SMA) scores, and the biochemical effects on lung tissue were assessed by interleukin-1 beta (IL-1ß), IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α). RESULTS: The alveolar surface area and fibrosis scores were found to be significantly higher in HILI groups compared with Group 1 (P < 0.01). The SMA scores in HILI groups were also significantly higher than Group 1 (P < 0.01). Bosentan treatment, especially late therapy, reduced all of these histopathological scores and the levels of IL-6 and TNF-α in the hyperoxia groups (P < 0.01). CONCLUSION: This experimental study showed that bosentan had a protective effect on hyperoxic lung injury through its anti-inflammatory properties.

Ischemia-modified albumin in preterm infants born to mothers with pre-eclampsia.

BACKGROUND: Pre-eclampsia (PE) carries an increased risk for maternal and/or fetal mortality or serious morbidity. PE is associated with ischemia and increased oxidative stress in the placenta, which may lead to modification of plasma albumin to ischemia-modified albumin (IMA). The aim of this study was to investigate IMA and hematological parameters in mothers and in premature infants in normal and in pre-eclamptic pregnancies. METHODS: Twenty-five pregnant women with PE and their premature newborns were categorized as the PE group, and 25 normotensive pregnant women and their premature newborns as the control group. Preterm infants are classified as small for gestational age (SGA) or non-SGA according to the Fenton preterm growth chart. Serum IMA, complete blood count (CBC), liver function tests (LFT), renal function tests (RFT), albumin, and C-reactive protein were measured in the mothers immediately before birth, and in the cord blood and serum of the newborns at 6 and 24 h after birth. Clinical and demographic data were recorded for both groups. RESULTS: While IMA, LFT and RFT were significantly increased in the PE group compared with the control group, albumin and CBC were significantly lower in the PE group. A total of 40% of PE newborns were SGA, 30% of whom had severe SGA (birthweight <3rd percentile). Cord IMA was significantly increased in all preterm neonates in the PE group compared with the control group. No mothers or neonates died. CONCLUSION: Serum IMA in addition to the prevalence of SGA were significantly increased in the PE group. Cord blood IMA, therefore, might be a predictive biomarker for SGA in PE pregnancies.

Analysis of centrosome and DNA damage response in PLK4 associated Seckel syndrome.

Microcephalic primordial dwarfism (MPD) is a group of autosomal recessive inherited single-gene disorders with intrauterine and postnatal global growth failure. Seckel syndrome is the most common form of the MPD. Ten genes are known with Seckel syndrome. Using genome-wide SNP genotyping and homozygosity mapping we mapped a Seckel syndrome gene to chromosomal region 4q28.1-q28.3 in a Turkish family. Direct sequencing of PLK4 (polo-like kinase 4) revealed a homozygous splicing acceptor site transition (c.31-3 A>G) that results in a premature translation termination (p.[=,Asp11Profs*14]) causing deletion of all known functional domains of the protein. PLK4 is a master regulator of centriole biogenesis and its deficiency has recently been associated with Seckel syndrome. However, the role of PLK4 in genomic stability and the DNA damage response is unclear. Evaluation of the PLK4-Seckel fibroblasts obtained from patient revealed the expected impaired centriole biogenesis, disrupted mitotic morphology, G2/M delay, and extended cell doubling time. Analysis of the PLK4-Seckel cells indicated that PLK4 is also essential for genomic stability and DNA damage response. These findings provide mechanistic insight into the pathogenesis of the severe growth failure associated with PLK4-deficiency.

Neonatal Bartter syndrome with cholelithiasis and hydrocephalus: Rare association.

Neonatal Bartter syndrome (NBS) is a rare autosomal recessive renal tubular disorder. This disease is characterized by hypokalemia, hypochloremia, and metabolic alkalosis that is often associated with failure to thrive and recurrent episodes of dehydration. The combination of BS and cholelithiasis in an infant is very rare. Herein, we report a premature male infant with NBS who developed cholelithiasis and hydrocephalus on clinical follow up. We recommend that periodic routine hepatobiliary ultrasonograpic screening for cholelithiasis should be performed in patients with NBS.