佐藤 洋明

BACKGROUND: The primary bile acids found in meconium vary with the gestational age of the fetus and the intestinal location of the meconium. We determined the composition of bile acids in samples that were collected from the gallbladder and intestine. METHODS: The bile-acid profiles of intestinal contents and the gallbladder were obtained from nine fetuses who died from abortion or respiratory failure within 72 h after birth. Intestinal content samples were collected from seven intestinal locations. The bile-acid profiles of meconium were also obtained from seven full-term live births for comparison. The profiles were analyzed using liquid chromatography-tandem mass spectrometry. RESULTS: The bile acids in meconium collected from stillborn and live births were mainly chenodeoxycholic acid and cholic acid, conjugated with taurine, glycine, and sulfate. The same bile acids were found in the gallbladder, except that sulfate was not found. CONCLUSIONS: Sulfate-conjugated bile acid is found in urine, but rarely in stool. In this study, the gallbladder bile acid contained no sulfate conjugates, but these were present in intestinal contents and meconium. These results indicate that sulfate-conjugated bile acids are not excreted into the intestine through the biliary tract but originate from swallowed amniotic fluid that contains fetal urine.

Aim Periventeicular leukomalacia (PVL) is one of the most important causes of adverse outcome of preterm infants We hypothesized that inflammatory or some other specific pathways will have been activated at birth in preterm infants who later develop PVL The aim of this study is to examine the difference in mRNA expression in umbilical cord blood according to the presence or absence of PVL Methods A total of 61 umbilical cord blood samples were collected from preterm infants with gestational age less than 33 weeks together with the patients medical information during perinatal period RNA expression patterns in the collected cord bloods were analyzed by microarray On the basis of cranial ultrasonography and brain MRI examination 3 infants (4 9%) were diagnosed as cystic PVL and selected as the subjects Five patients who showed similar perinatal factors to those of infants with PVL but did not show PVL were selected as the normal control Results Five of the 15 up-regulated genes are coding ribosomal proteins and another encodes a translation elongation factor Three of the 7 down-regulated genes encode proteins that may be related to immune response and/or inflammation Conclusions Up-regulation of the ribosomal proteins may indicate an activation of lymphocytes during the fetal period (C) 2010 Elsevier Ireland Ltd All rights reserved

Background: Neonatal sepsis is difficult to diagnose and pathogens cannot be detected from blood cultures in many cases. Development of a rapid and accurate method for detecting pathogens is thus essential. The main purpose of this study was to identify etiological agents in clinically diagnosed neonatal sepsis using bacterial ribosomal RNA-targeted reverse transcription-quantitative PCR (BrRNA-RT-qPCR) and to conduct comparisons with the results of conventional blood culture. Since BrRNA-RT-qPCR targets bacterial ribosomal RNA, detection rates using this approach may exceed those using conventional PCR. Methods: Subjects comprised 36 patients with 39 episodes of suspected neonatal sepsis who underwent BrRNA-RT-qPCR and conventional blood culture to diagnose sepsis. Blood samples were collected aseptically for BrRNA-RT-qPCR and blood culture at the time of initial sepsis evaluation by arterial puncture. BrRNA-RT-qPCR and blood culture were undertaken using identical blood samples, and BrRNA-RT-qPCR was performed using 12 primer sets. Results: Positive rate was significantly higher for BrRNA-RT-qPCR (15/39, 38.5%) than for blood culture (6/39, 15.4%; p = 0.0039). BrRNA-RT-qPCR was able to identify all pathogens detected by blood culture. Furthermore, this method detected pathogens from neonates with clinical sepsis in whom pathogens was not detected by culture methods. Conclusions: This RT-PCR technique is useful for sensitive detection of pathogens causing neonatal sepsis, even in cases with negative results by blood culture.

Background: Lower gastrointestinal bleeding (LGB), particularly in newborns, is of serious concern and requires urgent investigation and hospital care. Whereas allergic proctocolitis caused by food protein is a significant cause of LGB in infants with eosinophilia, there are several cases of diseases with symptoms similar to those of allergic proctocolitis but without an apparent allergic reaction influence. Patients and Methods: We examined 2 neonates using rectosignioidoscopy who showed eosinophilia and experienced fresh LGB soon after birth and before their first feedings. Serum eosinic cationic protein (ECP) and platelet activating factor (PAF) levels were also examined in the second case to confirm the involvement of eosinophils for its pathogenesis. Results: Both patients were in a clinically stable condition, and their abdomens were soft. The results of their blood analyses, abdominal radiographs, and stool cultures were normal, but they had gross eosinophilia: the eosinophil counts were 9014/mm(3) (patient 1) and 1955/mm 3 (patient 2). Rectosigmoidoscopy with colonic mucosal biopsy revealed nodular lymphoid hyperplasia with a pale mucosal surface and massive oozing with diffuse eosinophilic infiltration in the lamina propria. In patient 2 the serum ECP and PAF levels were elevated to 123 mu g/L (normal, < 14.7) and 13.1 mu mol/L/ min (normal, < 6). A few days after intravenous hydration therapy, LGB was no longer detected, and the serum ECP and PAF levels returned to normal. Conclusions: Inasmuch as these infants had LGB similar to allergic proctocolitis without any allergic reactions, we suggest that infiltrated eosinophils in the colonic mucosa could be involved in the pathogenesis of LGB in early infancy.

Objectives: Short-chain fatty acids (SCFAs) are known to provide energy to colonocytes, whereas overproduction of SCFAs can cause mucosal injury in premature infants. Our objective was to investigate the effects of the oral administration of Bifidobacterium breve M-16V (B breve) on fecal lactic acid and SCFAs in low birth weight (LBW) infants. Patients and Methods: Fecal lactic, acetic, propionic, and butyric acids from 66 premature infants were analyzed by high-performance liquid chromatography at 0, 2, and 4 weeks after birth. The subjects included 22 extremely LBW (ELBW, < 1000g), 22 very LBW (VLBW, < 1500g), and 22 LBW (< 2500g) infants. The infants were divided into two groups: those with and those without B. breve supplementation. Results: In the control groups, fecal acetic acid and total SCFA concentrations were significantly increased at 2 weeks in the VLBW and LBW infants (P < 0.05) and at 4 weeks in the ELBW, VLBW, and LBW infants (P < 0.01 for each) compared with those at week 0. Fecal lactic acid concentrations showed a similar pattern during follow-up, but the differences were not significant. Four weeks after B breve administration, the fecal butyric acid concentrations were significantly decreased in the ELBW and VLBW infants (P < 0.05 each), and the ratio of the acetic acid concentrations to the total SCFAs was significantly increased compared with those of the control groups in the ELBW (P < 0.05), VLBW (P < 0.05), and LBW infants (P < 0.01). Conclusions: Oral administration of B breve reduces the production of butyric acid, which may be helpful in protecting LBW infants from digestive diseases such as necrotizing enterocolitis.

Objectives: Transforming growth factor (TGF) beta 1 displays a broad spectrum of activities in mucosal regulation, including induction of oral tolerance, potent anti-inflammatory effects, mucosal IgA expression and effects on epithelial cell proliferation and differentiation. The present study examined the effect of probiotics on the immunologic system of preterm infants in relation to TGF-beta signaling. Methods: Subjects comprised 19 preterm infants divided into 2 groups: receiving Bifidobacterium breve supplementation (B. breve group) and without supplementation (controls). Blood samples were collected from both groups on days 0, 14 and 28 after birth. Serum cytokine levels were measured using enzyme-linked immunosorbent assay, and expression levels of the TGF-beta signaling molecule, Smad, were examined using semiquantitative reverse transcriptase-polymerase chain reaction. Results: Serum TGF-beta 1 level was elevated on day 14 and remained elevated on day 28 in the B. breve group. Level of messenger RNA expression was enhanced for Smad3 and reduced for Smad7 (antagonistic Smad) after B. breve administration relative to levels in controls on day 28. Conclusions: These results demonstrated that the administration of B. breve to preterm infants can up-regulate TGF-beta 1 signaling and may possibly be beneficial in attenuating inflammatory and allergic reactions in these infants.

The authors recently encountered a lethal case of Down syndrome with transient abnormal myelopoiesis (TAM). Although the peripheral white blood cell count and blast cells had improved without specific treatment, the patient died of severe coagulopathy due to liver fibrosis when he was 5 years old. The prognosis of TAM with liver fibrosis was poor. The patient had high levels of N-terminal peptide of III procollagen, type IV collagen, and hyaluronic acid. These serum makers are noninvasive indicators of liver fibrosis and may be useful as prognostic indicators of TAM in Down syndrome.