Akihiko Endo

Endogenous nitric oxide and endothelin-1 in persistent pulmonary hypertension of the newborn

Abstract We studied changes in endogenous nitric oxide (NO) synthesis and endothelin-1 (ET-1) production in infants with persistent pulmonary hypertension of the newborn (PPHN). We determined concentrations of serum NO metabolites, i.e., nitrites and nitrates (NOx), and of plasma ET-1 in five infants with PPHN (PPHN group) and in 25 healthy full-term neonates (control group). In both groups, serum NOx concentrations increased over time and plasma ET-1 concentrations decreased with age. The differences in serum NOx concentrations between groups were not significant at <12 h and 24 h of age; however, they were significantly higher in the PPHN group than in the control group at 5 days of age. The differences in plasma ET-1 concentrations between groups were not significant at 5 days of age, but were significantly higher in the PPHN group than in the control group at <12 h and 24 h of age. Conclusion Limited endogenous nitric oxide synthesis and elevated endogenous endothelin-1 production during the first few days of life may contribute to pulmonary hypertension in infants with persistent pulmonary hypertension of the newborn.

Nitric Oxide and Endothelin 1 during Postnatal Life

Nitric oxide (NO) is a potent vasodilator produced by endothelial cells. Endothelin 1 (ET-1), another agent made by endothelial cells, is the most potent vasoconstrictor known to date. Endogenous NO and ET-1 may play a part in the normal physiological pulmonary vascular changes during the postnatal period. However, the changes of NO and ET-1 in healthy neonates have not been defined. We determined serum NO metabolites, i.e., nitrites and nitrates, and plasma ET-1 in 19 healthy neonates at birth (cord blood) and at ages 5 and 30 days. The sums of serum nitrite and nitrate (NOx) levels were 27.5 +/- 12.8, 53.8 +/- 14.2, and 38.3 +/- 13.2 mumol/l at birth, age 5 days, and age 30 days, respectively. The plasma ET-1 concentrations were 3.9 +/- 1.6, 1.1 +/- 0.2, and 1.1 +/- 0.2 x 10(6) mumol/l at birth, age 5 days, and age 30 days, respectively. These changes in healthy neonates suggest the presence of active physiological roles for NO and ET-1 in circulatory adaptation to extra-uterine life.

Hypocapnia under hypotension induces apoptotic neuronal cell death in the hippocampus of newborn rabbits.

We investigated the adverse effect of hypocapnia on the neonatal rabbit brain. Two-week-old Japanese white rabbits were assigned to three groups, hyperventilation (H group), ischemia (I group), or hypocapnia with ischemia (HI group) and then subjected for 1.5 h with simultaneous measurement of the mean arterial blood pressure (MABP) and intracranial Hb concentration changes. Marked reductions of Paco2 and MABP were induced in the hyperventilation-loaded groups and the ischemia-loaded groups, respectively. The intracranial oxyhemoglobin and total Hb concentrations decreased slightly in the H group and markedly in the I and HI groups after the start of experimemtal protocols, although there were no statistical differences between the I and HI groups. Animals were killed at 24 h after experiments and then subjected to pathologic examination. Damaged neurons with shrunken cell bodies and nuclear changes were found on light microscopic examination, mainly in the pyramidal cell layer of the subiculum and cornu ammonis 1. The numerical density of damaged neurons was significantly higher in the HI group than those in the H or I groups (p < 0.05). These damaged neurons were positive on DNA nick end labeling. A DNA ladder was detected on electrophoresis with a DNA sample extracted from hippocampal tissue in the HI group, but not in the other two groups. On electron microscopic examination, not only condensation of the nucleus but also disruption of mitochondria and the cell membrane were detected. These results suggested that hypocapnia under hypotension might cause neuronal cell death in the hippocampus of neonatal rabbit. Not only ischemia but also a metabolic change induced by hypocapnia might contribute to this apoptotic neuronal cell damage.

Facial palsy associated with mumps parotitis.

Peripheral facial nerve paralysis is relatively common in the pediatric age group. However, facial palsy rarely has been documented in patients with mumps parotitis. This case report describes the findings of a 3-year-old Japanese boy who developed facial palsy immediately after mumps parotitis. This work calls attention to a possible association between mumps parotitis and facial palsy.

Physiologic significance of nitric oxide and endothelin-1 in circulatory adaptation

Abstract Background: The purpose of the present paper was to evaluate the physiologic significance of nitric oxide (NO) and endothelin (ET)‐1 in circulatory adaptation in the neonate.

Developmental expression of myotonic dystrophy protein kinase in brain and its relevance to clinical phenotype.

Abstract To investigate the pathophysiologic role of myotonic dystrophy protein kinase (DMPK) in the brain in myotonic dystrophy (MD), the developmental characteristics of DMPK immunoreactivity in the central nervous system and its alteration with disease were studied. Eleven patients’ brain with MD (5 congenital form, 6 adult form) were examined by immunohistochemistry using a specific antibody against synthetic DMPK peptides, anti-peptide DM1, and compared with 30 control brains, including 16 age-matched controls. In controls, DM1-immunoreactive neurons appeared in the early fetal frontal cortex and cerebellar granule cell layer, persisting through 29 weeks of gestation and then disappearing. In contrast, immunoreactive neurons continued to persist in the cerebral cortex and cerebellar granule cell layer of MD patients. When we counted DM1-immunoreactive neurons, the increase over controls was greater in the congenital form of MD than in the adult form, and was greater in the cerebrum than in the cerebellum in both forms of MD. DM1 immunostaining was predominantly nuclear, mirroring Western blotting of subcellular fractions. Differences in DM1 expression related to development and to the two forms of MD may be closely related to the pathogenesis of mental retardation in this disease.

Endothelium-derived relaxing and contracting factors during the early neonatal period

Abstract The interaction and relative potency of nitric oxide, an endothelium‐derived relaxing factor, and endothelin‐1, an endothelium‐derived contracting factor, may be important in the transition from fetal to extrauterine life. The change in level of nitric oxide during the early neonatal period has not been measured. Accordingly, the serum levels of nitric oxide metabolites (the sum of nitrite and nitrate) and plasma endothelin‐1 were determined in 20 healthy neonates at birth, at 12 and 24 h postnatally, and at the age of 5 d. The lowest serum concentration of nitric oxide metabolites was observed at birth (26.2 ± 9.1 µmol 1‐1, mean ± SD) and increased with age, whereas the highest plasma concentration of endothelin‐1 was observed at birth (14.0 ± 6.7 pg ml‐1) and decreased with age. These changes suggest that nitric oxide and endothelin‐1 play roles in the circulatory adaptation of the neonate to extrauterine life.

Spontaneous labor increases nitric oxide synthesis during the early neonatal period

Abstract Background : This paper aimed to assess the influence of spontaneous labor upon endogenous nitric oxide (NO) and endothelin 1 (ET‐1) during transition to extrauterine life.

Ring chromosome 17 syndrome with monosomy 17 mosaicism : case report and literature review

children described here the bleeding was due to covert biting of the buccal mucosa; a potential explanation not previously highlighted in the medical literature. The recurrent episodes of bleeding in cases 1 and 2 caused great anxiety to their families and resulted in long periods of absence from school. The children underwent extensive medical investigation over periods of 3 and 12 mo. Numerous blood tests were performed, and the children were subjected to multiple invasive procedures, including upper gastrointestinal endoscopy, laryngoscopy and bronchoscopy. Case 1 was admitted to hospital for observation on seven occasions and case 2 on three occasions. Because of the bizarre nature of the clinical presentation and because extensive investigations had failed to establish a diagnosis, Munchausen-by-proxy might have been suspected in these cases. Indeed, in case 1 the father was concerned that his account of events was not believed. No hospital personnel had reported witnessing an episode during the course of numerous admissions to hospital. Although Munchausen-by-proxy is more often perpetrated by women, a recent report emphasized than this behaviour pattern may also occur with men (4). In order to support a diagnosis of Munchausen-by-proxy in these cases, it would have been necessary to postulate collusion, both children being 10-y-old, but such collusion has been reported (5). In case 3 there were persistent gastrointestinal symptoms, but investigations had proved negative. Several aspects of the history, including reports of bullying at school, pointed to a possible psychological basis for these complaints. Ultimately, when he presented with an episode of haematemesis, recognition of the self-inflicted bite injuries clarified the need for psychological intervention. During the episodes of bleeding these children appeared to be in distress, and as they drooled bloods ained saliva from the mouth, their parents interpreted their vocal utterances as being due to either vomiting or coughing. In cases 1 and 2 demonstration of high levels of salivary amylase was useful in establishing the diagnosis. Cases 1 and 2 were examined on several occasions and case 2 was referred to an otorhinolaryngologist who performed a thorough examination of the oral cavity. No evidence of injury to the oral mucosa was found. This may be explained by the capacity of the buccal mucosa for rapid healing. In each of these children inspection of the oral cavity immediately after an episode of bleeding revealed the tell-tale mucosal bite-marks.

A case of pulmonary hypoplasia associated with intrauterine brainstem necrosis

Abstract. An infant with intrauterine brain death accompanied by pulmonary hypoplasia is reported. The fetus was delivered after 36 weeks gestation, 5 weeks after fetal movements ceased. The child died 4 h after birth. Pulmonary hypoplasia and remote brainstem necrosis associated with multicystic encephalomalacia were found at autopsy. Conclusion: these findings suggest that damage to brainstem respiratory centres had led to pulmonary hypoplasia through the absence of fetal respiratory movement.