Twenty-year trends in neonatal surgery based on a nationwide Japanese surveillance program.

AIM: To discuss the chronological changes observed in a national survey of neonatal surgery in Japan performed every 5 years by the Committee in the Japanese Society of Pediatric Surgeons. METHODS: We analyzed the data obtained for 20 years from 1993 to 2013 and herein report the chronological changes. RESULTS: The number of summarized cases was least in 1993, with 2806 cases, and subsequently increased to 3753 cases in 2013. The mortality rate among the patients with maternal transport linearly decreased (p = 0.0386). Although the proportion of extremely low birth weight infants linearly increased (p = 0.0014), with an annual rate of +0.39 %, the mortality rate linearly decreased (p = 0.0010), with an annual rate of -1.68 %. Moreover, the overall mortality rate linearly decreased (p = 0.0002), with an annual rate of -0.26 %. Most diseases were observed to exhibit a decline in the mortality rate with the same trend as overall mortality. The decline in the mortality rate was most robust with respect to congenital diaphragmatic hernia (CDH). The mortality rates, except for that of CDH, omphalocele, esophageal atresia, and intestinal perforation, declined to 5 % or lower by 2013. CONCLUSIONS: The present findings may be the result of remarkable progress in perinatal management.

A baseline impedance analysis in neurologically impaired children: A potent parameter for estimating the condition of the esophageal mucosa.

BACKGROUND: The aim of the present study was to investigate whether the baseline impedance (BI) value is a useful parameter to evaluate the condition of the esophageal mucosa in neurologically impaired (NI) children undergoing multichannel intraluminal impedance pH measurements (pH/MII). METHODS: The retrospective study included 55 NI patients ≤15 years. The patients were divided into acid gastroesophageal reflux disease (GERD), non-acid GERD and GERD (-) groups. Furthermore, the patients in the acid GERD group were subdivided into erosive reflux disease (ERD) and non-erosive reflux disease (NERD) groups. pH/MII parameters and BI values (Z1-6) were compared among three groups or between two groups, respectively. A Spearman's correlation analysis was used for the correlation analysis of pH/MII parameters and BI values. A receiver operator characteristic curve analysis was used to evaluate the optimum cut-off values of BI to discriminate ERD patients. KEY RESULTS: The BI values of the proximal and the distal channels in ERD group were significantly lower than those in NERD group. The BI values of the distal channels demonstrated significant negative correlations with acid exposure related pH/MII parameters. The optimal cut off value of BI in the most distal channel was determined to be 1500 Ω. CONCLUSIONS & INFERENCES: The present study suggested that NI children with reflux esophagitis were likely to suffer mucosal damage up to the proximal esophagus and cut-off BI values may help estimate the presence of reflux esophagitis. Baseline impedance is a potent parameter, reflecting the esophageal mucosal damage in NI children who have difficulty in undergoing endoscopic examinations.

Nafamostat mesilate, a serine protease inhibitor, suppresses lipopolysaccharide-induced nitric oxide synthesis and apoptosis in cultured human trophoblasts.

We investigated the effects of nafamostat mesilate, a synthetic protease inhibitor clinically used for patients with pancreatitis or disseminated intravascular coagulopathy, on NO synthesis and apoptosis in lipopolysaccharide (LPS)-treated human trophoblasts. Nafamostat mesilate or aminoguanidine, an inhibitor of NO synthase, suppressed NO synthesis and apoptosis in trophoblasts induced by LPS. Both agents also suppressed matrix metalloproteinase-2 activity induced by LPS. LPS also stimulated secretion of IL-6 and IL-8 in cultured trophoblasts, which was suppressed by nafamostat mesilate. Protease inhibitors including nafamostat mesilate may be therapeutic agents for chorioamnionitis and various diseases including septic shock, ischemia-reperfusion injury in brain and heart, graft rejection, and acute phase inflammatory diseases, in which overproduction of NO or peroxynitrite is involved in tissue injury.

The antioxidant effect of green tea catechin ameliorates experimental liver injury.

PURPOSE: Several studies have reported green tea catechin to have both antifibrotic and anti-oxidative effects. The goal of this study was to evaluate the effect of green tea cathechin therapy in hepatic tissue injury using cholestatic rats with bile duct ligation. MATERIALS AND METHODS: We performed bile duct ligation on cholestatic seven-week-old male Wistar rats and classified them into three groups according to the method of treatment. The groups comprised the SHAM group, the NT-group (no-treatment-group), and the T-group (treatment-group). The rats were orally administered green tea catechin at a dose of 50mg/kg/day and were sacrificed on the 17th postoperative day. We subsequently investigated the levels of fibrosis and antioxidant activity associated with various clinical markers. We evaluated the serum AST and ALT levels and performed immunohistochemical analyses for 4-hydroxynonenal (4-HNE), 8-oxo-2'deoxyguanosine (8-OHdG) and transforming growth factor-beta1 (TGF-beta1). We also evaluated the levels of activator protein-1 m-RNA (AP-1 m-RNA) and tissue inhibitor metalloproteinase-1 m-RNA (TIMP-1 m-RNA) by Real Time PCR. Finally, we performed Azan staining and immunohistochemical staining of alpha-smooth muscle actin (alpha-SMA) to evaluate the degree of fibrosis. RESULTS: The values of serum AST, serum ALT, AP-1 m-RNA, alpha-SMA, TGF-beta1, 4-HNE, and 8-OHdG in the T-Group were significantly lower than those in NT-Group. Therefore, the administration of green tea catechin might have suppressed the oxidative stress, controlled the stellate cell activation and consequently reduced the fibrosis. CONCLUSION: Green tea catechin may reduce hepatic fibrosis by suppressing oxidative stress and controlling the transcription factor expression involved in stellate cell activation.

GnRH agonist-suppressed expression of nitric oxide synthases and generation of peroxynitrite in adenomyosis.

Because overproduction of nitric oxide (NO) and peroxynitrite is known to cause tissue injury, the expression of NO synthases (NOS) and generation of peroxynitrite were investigated in adenomyosis. Immunoreactivities to endothelial and inducible NOS demonstrated phase-dependent changes in normal endometrium, and in eutopic endometrium of adenomyosis. However, NOS were expressed throughout the menstrual cycle in ectopic endometrium from the majority of patients with adenomyosis. Nitrotyrosine, a footprint of peroxynitrite, was detected concomitantly with NOS protein. This suggested that high doses of NO and superoxide are produced in the ectopic endometrium, presumably by stimulation with bioactive molecules such as cytokines and growth factors. The expression of NOS and generation of peroxynitrite were markedly reduced by administration of gonadotrophin-releasing hormone agonists (GnRHa). The suppression of serum concentrations of nitrite/nitrate, stable metabolites of NO, by long-term administration of GnRHa was also demonstrated. The suppression of synthesis of NO and/or peroxynitrite may be part of both the therapeutic and adverse effects of GnRHa therapy.

Generation of peroxynitrite and apoptosis in placenta of patients with chorioamnionitis: possible implications in placental abruption.

The reaction of nitric oxide (NO) and superoxide results in the formation of peroxynitrite, a potent and relatively long-lived oxidant. In infectious diseases, these molecules are not only bactericidal but also toxic to host cells. Chorioamnionitis is often complicated by premature rupture of membranes and can be associated with placental abruption. These diseases are significant causes of premature low-birth-weight deliveries and consequently the morbidity and mortality of neonates. Lipopolysaccharide, bacterial endotoxin, is known to be elevated in the amniotic fluid of patients with chorioamnionitis. Lipopolysaccharide is known to induce the formation of NO and superoxide. We report here that nitrite/nitrate, stable metabolites of NO, were increased in serum from patients with chorioamnionitis. Immunohistochemical studies demonstrated enhanced expression of inducible NO synthase and formation of nitrotyrosine, a footprint of peroxynitrite, in the placentae from patients with chorioamnionitis and also in patients with placental abruption. Furthermore, apoptotic cell death was also increased in the placentae from patients with both diseases. These results suggest that chorioamnionitis and a portion of placental abruption may share a common cascade of placental injury. Nitric oxide and its metabolities may play an important role in this cascade.

Elevated blood flow resistance in uterine arteries of women with unexplained recurrent pregnancy loss.

BACKGROUND: Uterine perfusion appears to regulate uterine receptivity. However, vascular changes in recurrent pregnancy loss (RPL) remain poorly studied. METHODS: One hundred and twenty one women were enrolled into this study: normal women with sterility caused by male factor (control group: n = 72) and women with RPL (n = 49). Women with uterine anomaly, impaired glucose tolerance, abnormal thyroid function, or anti-phospholipid antibodies were excluded from the study. In the mid-luteal phase of a non-pregnant cycle, transvaginal pulsed Doppler ultrasonography of the uterine artery was performed. Uterine arterial pulsatility index (PI), endometrial thickness, serum estradiol, progesterone, and nitrite/nitrate concentrations were determined. RESULTS: In the RPL group, the PI in the uterine artery of women with antinuclear antibodies was significantly higher than that of women without antinuclear antibodies (P < 0.05). Among women without antinuclear antibodies, the mean (+/-SD) uterine artery PI in the RPL group (2.44 +/- 0.41) was also significantly higher than in the control group (2.19 +/- 0.40; P < 0.01). The PI was inversely correlated with serum progesterone levels (r = -0.47, P < 0.01). CONCLUSIONS: Elevated uterine arterial impedance is associated with RPL. Pulsed Doppler ultrasonography is useful in identifying women with unexplained RPL who have impaired uterine circulation.

Clinical experience of long-term transdermal treatment with nitric oxide donor for women with preeclampsia.

Isosorbide dinitrate (ISDN), a nitric oxide donor, was applied transdermally for 4-16 days to 4 preeclamptic women with oligohydramnios, intrauterine fetal growth retardation (IUGR), and elevated resistance of blood flow in the uterine arteries. Pulsed Doppler ultrasonography revealed immediate and drastic improvement of pulsatility index (PI) of uterine arteries following treatment with ISDN. The average PI in uterine arteries of the 4 patients was reduced to approximately 67% of that of the untreated state. In 2 patients the amniotic fluid gradually increased over a few days which suggested improvement of fetoplacental circulation during administration of ISDN. This study suggests that long-term transdermal ISDN is an effective therapy, at least in a portion of preeclamptic women, to avoid maternal hypertension, fetal distress, oligohydramnios, and IUGR, and consequentially to prolong the gestational period.