Neonatal Rat Necrotizing Enterocolitis Model Adopting Oral Endotoxin and Hypoxia Exhibits Increased Apoptosis through Caspase-3 Activation

PURPOSE: The aim of this study was to develop a model for necrotizing enterocolitis (NEC) in the neonatal rat using endotoxin and hypoxia, a plausible insult in a neonatal intensive care and to investigate the role of apoptosis as the underlying mechanism. METHODS: Newborn rats were given oral endotoxin and intermittent 8% hypoxia+/-caspase inhibitor. The intestinal histology was evaluated using hematoxylin-eosin staining. Apoptosis was analyzed with TUNEL staining and by measuring the caspase 3 activity in the intestinal lysates. IEC-6 cells were assessed for apoptosis and the expression of Bax, Bcl-2, Fas and FasL was measured after treatment with endotoxin and hypoxia. RESULTS: Oral endotoxin (5 mg/kg) and exposure to 8% hypoxia of 60-min duration twice induced human NEC-like lesions in the rat intestine. Intestinal tissue revealed increased apoptosis and caspase-3 activity. After caspase inhibitor treatment, the grades of both apoptosis and NEC were significantly reduced. IEC-6 cells exhibited increased apoptosis and caspase 3 activity after endotoxin and hypoxia treatment and significantly increased Bax/Bcl-2 ratio compared to control cells. CONCLUSION: This neonatal rat model of NEC which was induced by oral endotoxin and intermittent hypoxia showed increased apoptosis of intestinal epithelial cells that was mediated by caspase 3 activation. Our model has a advantage in the study of NEC because the use of much more clinically plausible insults may provide a suitable model for the investigation of its pathophysiology and therapeutic trials.

The Stem Bark of Kalopanax pictus Exhibits Anti-inflammatory Effect through Heme Oxygenase-1 Induction and NF-kappaB Suppression

BACKGROUND: The stem bark of Kalopanax pictus (KP) has been used in traditional medicine to treat rheumatoidal arthritis, neurotic pain and diabetes mellitus in China and Korea. In this study, the mechanism responsible for anti-inflammatory effects of KP was investigated. METHODS: We examined the effects of KP on NO production, nitric oxide synthase (iNOS) and HO-1 expression, NF-kappaB, Nrf2 and MAPK activation in mouse peritoneal macrophages. RESULTS: The aqueous extract of KP inhibited LPS-induced NO secretion as well as inducible iNOS expression, without affecting cell viability. KP suppressed LPS-induced NF-kappaB activation, phosphorylation and degradation of IkappaB-alpha, phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Furthermore, KP induced HO-1 expression and Nrf2 nuclear translocation. CONCLUSION: These results suggest that KP has the inhibitory effects on LPS-induced NO production in macrophages through NF-kappaB suppression and HO-1 induction.

AMP kinase/cyclooxygenase-2 pathway regulates proliferation and apoptosis of cancer cells treated with quercetin

AMPK (AMP-activated protein kinase) is highly conserved in eukaryotes, where it functions primarily as a sensor of cellular energy status. Recent studies indicate that AMPK activation strongly suppresses cell proliferation in non-malignant cells as well as in tumor cells. In this study, quercetin activated AMPK in MCF breast cancer cell lines and HT-29 colon cancer cells, and this activation of AMPK seemed to be closely related to a decrease in COX-2 expression. The application of a COX-2 inhibitor or cox-2(-/-) cells supported the idea that AMPK is an upstream signal of COX-2, and is required for the anti-proliferatory and pro-apoptotic effects of quercetin. The suppressive or growth inhibitory effects of quercetin on COX-2 were abolished by treating cancer cells with an AMPK inhibitor Compound C. These results suggest that AMPK is crucial to the anti-cancer effect of quercetin and that the AMPK-COX-2 signaling pathway is important in quercetin-mediated cancer control.

Comparison of foodservice management performance level between dietitians and non-dietitians in senior centers using IPA

This study investigated the management importance and performance level of foodservice managers at senior centers. Using the survey, perceived importance and performance levels of seven foodservice management areas were evaluated and analyzed. Data showed the foodservice facilities were being managed by dietitians (61.6%) or non-dietitians (38.9%). The result indicated that overall importance level (3.43) was higher than performance level (3.02) (p<.01). As of the IPA result, dietitians and non-dietitians had different perspectives in terms of managing the eight categories of foodservice areas. The differences in the IPA results between the two groups may reflect bias attributable to the respondents' degrees of knowledge and professional preparation. The research findings could enhance our understanding of importance of hiring professional dietitians to operate foodservice at senior centers and find out which management area should be concentrated for more effective foodservice management.

Decreased Expression of Transforming Growth Factor-beta1 in Bronchoalveolar Lavage Cells of Preterm Infants with Maternal Chorioamnionitis

Maternal chorioamnionitis has been associated with abnormal lung development. We examined the effect of maternal chorioamnionitis on the expression of transforming growth factor-beta1 (TGF-beta1) in the lungs of preterm infants. A total of 63 preterm (< or =34 weeks) infants who were intubated in the delivery room were prospectively enrolled. Their placentas were examined for the presence of chorioamnionitis. Bronchoalveolar lavage (BAL) fluid and cells were obtained shortly after birth. TGF-beta1 was measured in BAL fluid and TGF-beta1 mRNA expression was determined by reverse transcription polymerase chain reaction (RT-PCR) in BAL cells. TGF-beta1 mRNA expression in BAL cells showed a positive correlation with gestational age (r=0.414, p=0.002). TGF-beta1 mRNA expression was significantly decreased in the presence of maternal chorioamnionitis (0.70+/-0.12 vs. 0.81+/-0.15, p=0.007). Adjustment for gestational age, birth weight, and delivery mode did not nullify the significance. TGF-beta1 mRNA expression was marginally significantly decreased in preterm infants who developed bronchopulmonary dysplasia (BPD) later (0.75+/-0.11 vs. 0.82+/-0.15, p=0.055). However, adjustment for gestational age, patent ductus arteriosus (PDA), and maternal chorioamnionitis nullified the significance. These results might be an indirect evidence that maternal chorioamnionitis may inhibit normal lung development of fetus.

A Case of Congenital Methemoglobinemia Due to NADH-Methemoglobin Reductase Deficiency

Congenital methemoglobinemia is caused by NADH-methemoglobin reductase deficiency in more than half of the total reported cases. NADH-methemoglobin reductase deficiency is an uncommon hereditary disorder producing methemoglobinemia and cyanosis in the homozygous subject. A majority of the patients born with these abnormalities have only a cosmetic defect-asymptomatic cyanosis. Congenital methemoglobinemia due to NADH-methemoglobin reductase deficiency is an autosomal recessive disorder and classified into 4 types according to the pathophysiology of the disorder. In type I, the deficiency of NADH-methemoglobin reductase is restricted to erythrocytes of patients with mild cyanosis, and 7 missence mutations have been reported in the case of type I. We report the first Korean pediatric case of type I congenital methemoglobinemia due to NADH- methemoglobin reductase deficiency with a review of the literature.

Development of Bronchopulmonary Dysplasia and the Peripheral and Tracheal Aspirate Neutrophil Counts and Cytokine Concentrations of Tracheal Aspirate in Preterm Infants with Acute Respiratory Failure

PURPOSE: The purposes of this study were to analyze the association of peripheral and tracheal aspirate neutrophil counts and tracheal aspirate cytokines [interleukin (IL)-8, IL-6, IL-10] concentrations with the development of bronchopulmonary dysplasia (BPD) in preterm infants intubated due to acute respiratory failure, and to speculate the causal relationship between the prenatal or early postnatal inflammation of the lung and the development of BPD. METHODS: A prospective study was conducted from April 1997 to March 1998 in 27 preterm infants, who were admitted to the neonatal intensive care unit of Seoul National University Children's Hospital and intubated due to acute respiratory failure. Tracheal aspirates were collected via endotracheal tube immediately after intubation. Tracheal aspirate neutrophil counts were measured by cytospin method and, cytokine concentrations were measured by ELISA method in the supernatant after centrifugation. RESULTS: BPD was diagnosed in 59.3% (16/27) of preterm infants. Compare to the non-BPD group, the BPD group had lower gestational age (27.6+/-1.3 weeks versus 32.0+/- 1.2 weeks), lower birth weight (1,112+/-228 g versus 1,666+/-334 g), higher incidence of patent ductus arteriosus (27.3% versus 81.3%), increased number of neutrophils (80,337+/-133,993/mL versus 2,672+/-6,600/mL), and increased IL-8 concentration (1,045.4+/-1,346.5 pg/mL vs 106.9+/-151.0 pg/mL) of tracheal aspirate. After control of compounding variables, increased IL-8 concentration of tracheal aspirate was found to be an independent risk factor for BPD (odds ratio; 27.7, 95% confidence interval; 1.8-436.2). CONCLUSION: Prenatal or immediate postnatal lung inflammation is an important risk factor for the development of the BPD, and the lung injuries responsible for the development of BPD might begin at the prenatal or immediate postnatal period.

Comparison of Continuous Versus Intermittent Infusion of Indomethacin in PDA of Preterm Infants

PURPOSE: Patent ductus arteriosus (PDA) of prematurity is very important disease to study because it causes many cases of perinatal morbidity and its incidence is now increasing. Nowadays indomethacin is the drug of choice for PDA closure, but its use has been limited due to its side effects. Therefore, we compared the effect and side effects of indomethacin according to the infusion method, continuous versus intermittent infusion, to find better an administration method. METHODS: Twenty-five preterm infants who were admitted to Seoul National University Children's Hospital (SNUCH) NICU from March 1995 to August 1996 with a diagnosis of respiratory distress syndrome (RDS) and PDA, were enrolled. They were randomly assigned to intertmittent lV group or continuous lV group. Each group received three intermittent doses or continuous infusion over 36 hours, respectively. We analyzed the perinatal history, time of diagnosis and treatment of PDA, size of PDA, and compared the laboratory parameters, intraventricular hemorrhage (IVH), periventricular echogenecity (PVE), ductal closure and perinatal morbidity before and 48 hours after indomethacin administration between the two groups. RESULTS: Fourteen infants (birth weight 1,149 +/- 373g) were intermittent lV group and eleven infants (birth weight 1,212 +/- 504g) were continuous lV group. There were no significant difference between the groups in perinatal history, pretreatment laboratory parameters, ductal closure, and perinatal morbidity. Patients with IVH of grade 2 or more increased significantly in intermittent lV group (50%) compared to continuous lV group (9%), and PVE progressed significantly in intermittent lV group (64%) compared to continuous lV group (18%). CONCLUSION: Continuous infusion of indomethacin for PDA closure in preterm infants with RDS appears to be as effective as intermittent infusion of indomethacin in closing PDA and have less side effects such as IVH and PVE progress.

Comparison of Continuous versus Intermittent Infusion of Indomethacin in PDA of Preterm Infants

PURPOSE: Patent ductus arteriosus (PDA) of prematurity is very important disease to study because it causes many cases of perinatal morbidity and its incidence is now increasing. Nowadays indomethacin is the drug of choice for PDA closure, but its use has been limited due to its side effects. Therefore, we compared the effect and side effects of indomethacin according to the infusion method, continuous versus intermittent infusion, to find better an administration method. METHODS: Twenty-five preterm infants who were admitted to Seoul National University Children's Hospital (SNUCH) NICU from March 1995 to August 1996 with a diagnosis of respiratory distress syndrome (RDS) and PDA, were enrolled. They were randomly assigned to intertmittent lV group or continuous lV group. Each group received three intermittent doses or continuous infusion over 36 hours, respectively. We analyzed the perinatal history, time of diagnosis and treatment of PDA, size of PDA, and compared the laboratory parameters, intraventricular hemorrhage (IVH), periventricular echogenecity (PVE), ductal closure and perinatal morbidity before and 48 hours after indomethacin administration between the two groups. RESULTS: Fourteen infants (birth weight 1,149 +/- 373g) were intermittent lV group and eleven infants (birth weight 1,212 +/- 504g) were continuous lV group. There were no significant difference between the groups in perinatal history, pretreatment laboratory parameters, ductal closure, and perinatal morbidity. Patients with IVH of grade 2 or more increased significantly in intermittent lV group (50%) compared to continuous lV group (9%), and PVE progressed significantly in intermittent lV group (64%) compared to continuous lV group (18%). CONCLUSION: Continuous infusion of indomethacin for PDA closure in preterm infants with RDS appears to be as effective as intermittent infusion of indomethacin in closing PDA and have less side effects such as IVH and PVE progress.

The Efficacy of Fetal Ultrasonography and Postnatal Abdominal Ultrasonography for the Diagnosis of Neonatal Abdominal Mass

PURPOSE: Most neonatal abdominal masses are benign in nature, but early detection and management is important to avoid the development of complications. So, we studied the causes of neonatal abdominal masses and the efficacy of ultrasonography for early detection and diagnosis. METHODS: We reviewed 36 newborn infants with abdominal masses who had been admitted to the nursery and Neonatal Intensive Cave Unit of Seoul National University Children' s Hospital from Jan. 1, 1989 to Dec. 31, 1995. RESULTS: The mean gestational age was 38 weeks and the male to female ratio was 22 : 14. All masses were benign and the most common etiology was hydronephrosis (41.7%). The following etiologies were multicystic dysplastic kidney, polycystic kidney, ovarian cyst, hemangioendothelioma, teratoma, meconium peritonitis, mesenteric cyst and intestinal duplication cyst. All except one were detected before the first 48hours, and among them, 32 cases (88.9%) detected antenatally. All patients except one who died shortly after birth, were examined by abdominal ultrasonography, and 31 of 35 masses (88.6%) had the same diagnosis of ultrasonography. Five cases had associated abnormalities in the opposite kidney and other organs. CONCLUSION: The most common etiology of neonatal abdominal masses was hydronephrosis and majority of masses originated from genitourinary system. Most abdominal masses were detected antenatally and abdominal ultrasonography was an efficient method for the diagnosis of neonatal abdominal masses.

Influence of Phototherapy on Incidence of Patent Ductus Arteriosus in Very Low Birth Weight Infants

PURPOSE: Patent ductus arteriosus (PDA) is a common disease in very low birth weight infants (VLBWI). Hemodynamically significant PDA increases the morbidity and mortality of premature infants. Based on experimental model, light inhibits the constriction of immature piglet's ductal rings. No specific mechanism adequately explains the effect of light on the relaxation of PDA. Several hypotheses, including activation of photosensitive metabolites, alterations in receptors, or alterations in prostaglandin metabolism, have been postulated. The purpose of this study was to evaluate the influence of phototherapy on incidence of PDA in VLBWI. Mehtods : Sixty-three infants with birth weights less than 1,500 gm from March 1994 to February 1996 who were admitted in NICU of Seoul National University Children's Hospital were included. Thirty-four infants from March 1995 to February 1996 were shielded with aluminium foils on left chest during phototherapy (Shield group) and twenty-nine infants from March 1994 to February 1995 were not shielded (No shield group : control group). We investigated the incidence and the perinatal risk factors of PDA. RESULTS: 1) The incidence of PDA was 18% in shield group and 41% in control group. There was statistically significant between the two groups (P<0.05). 2) There was not statistically significant between two groups with gestational age, birth weight, sex, delivery mode, etc. 3) The perinatal risk factors which were statistically significant were group and presence of respiratory distress syndrome (RDS), and use of artificial surfactant. With linear logistic regression analysis, only group (OR=8.3, 95% CI=1.17-58.69) and presence of RDS (OR=21.3, 95% CI=1.39-329.81) were proved to be related to the occurrence of PDA. CONCLUSIONS: We conclude that chest shielding during phototherapy is a simple and inexpensive method to decrease the incidence of PDA.