Kee Soo Ha

Postnatal early overnutrition dysregulates the intrarenal renin–angiotensin system and extracellular matrix-linked molecules in juvenile male rats

Overnutrition during the perinatal period has been associated with susceptibility to obesity and related comorbidities. We examined the effects of postnatal early overnutrition on the development of juvenile obesity and the associated renal pathophysiological changes. Three or 10 pups per mother from rat pup litters were assigned to either the overnutrition or control groups during the first 21 days of life. The effects of overfeeding were measured at 28 days. The smaller male litter pups were heavier than the controls between 4 and 28 days after birth (P<.05). By 28 days of age, the kidney weight per body weight ratio decreased in the small litter group (P<.05). Circulating leptin levels increased in the small litter rats (P<.05). Overnutrition had no effect on renal cell proliferation, apoptosis, macrophages and glomerulosclerosis. In the immunoblots and immunohistochemistry, renin and angiotensin II type (AT) 2 receptor expression increased in the overfed rats (P<.05). By contrast, the plasminogen activator inhibitor (PAI)-1 and matrix metalloproteinase (MMP)-9 expression decreased in the overnutrition group (P<.05). The AT 1 receptor, tissue inhibitor of MMP-1, monocyte chemoattractant protein-1, tumor necrosis factor-α, osteopontin and adiponectin expression was not changed. Our data showed that postnatal early overfeeding led to hyperleptinemia, juvenile obesity and the acquired reset of renal maturation. Up-regulation of renin and AT2 and down-regulation of PAI-1 and MMP-9 might contribute to abnormal programming of renal growth in rats exposed to postnatal early overnutrition.

Overweight, hypertension and renal dysfunction in adulthood of neonatally overfed rats

Accelerated growth in early infancy has been associated with later cardiovascular and metabolic diseases. We investigated the influence of overnutrition during neonatal periods on the development of renal pathophysiological changes in adult offspring rats. Three or 10 male pups per mother were assigned to either the small litter (SL) or normal litter (NL) control groups during the first 21 days of life. The effects of early postnatal overnutrition on body weight, blood pressure and renal changes were determined at 3 and 6 months. Pups in the SL group weighed more than controls between 7 days and 6 months of age (P<.05). In the SL group, serum creatinine levels were higher at 3 and 6 months (P<.05), and at 6 months, blood pressure levels were higher than those of the controls (P<.05). The number of ED-1 positive macrophages in renal cortex and glomerulosclerosis index increased in the SL group at 3 and 6 months (P<.05). Additionally, cortical apoptotic cells increased in the SL group at 6 months (P<.05). Immunoblotting and immunohistochemistry showed that matrix metalloproteinase (MMP)-9 protein expressions decreased and tissue inhibitor of MMP-1, tumor necrosis factor-α, osteopontin and adiponectin expressions increased in the SL group at 3 months (P<.05). However, at 6 months, MMP-9 expression was elevated, and osteopontin expression remained elevated in the SL group (P<.05). Early postnatal overfeeding can lead to lasting overweight, hypertension and renal dysfunction and place a greater burden on the kidney.

A genome-wide association analysis identifies NMNAT2 and HCP5 as susceptibility loci for Kawasaki disease

Kawasaki disease (KD), a systemic vasculitis of infants and children, manifests as fever and mucocutaneous inflammation. Although its etiology is largely unknown, the epidemiological data suggest that genetic factors are important in KD susceptibility. To identify genetic variants influencing KD susceptibility, we performed a genome-wide association study (GWAS) and replication study using a total of 915 children with KD and 4553 controls in the Korean population. Six single-nucleotide polymorphisms (SNPs) in three loci were associated significantly with KD susceptibility (P<1.0 × 10−5), including the previously reported BLK locus (rs6993775, odds ratio (OR)=1.52, P=2.52 × 10−11). The other two loci were newly identified: NMNAT2 on chromosome 1q25.3 (rs2078087, OR=1.33, P=1.15 × 10−6) and the human leukocyte antigen (HLA) region on chromosome 6p21.3 (HLA-C, HLA-B, MICA and HCP5) (rs9380242, rs9378199, rs9266669 and rs6938467; OR=1.33–1.51, P=8.93 × 10−6 to 5.24 × 10−8). Additionally, SNP rs17280682 in NLRP14 was associated significantly with KD with a family history (18 cases vs 4553 controls, OR=6.76, P=5.46 × 10−6). These results provide new insights into the pathogenesis and pathophysiology of KD.

Laboratory Markers in Incomplete Kawasaki Disease according to Coronary Artery Outcome

Background and Objectives We defined laboratory marker profiles typical of incomplete Kawasaki disease (iKD) during illness, especially with respect to the presence of a coronary artery abnormality such as coronary artery dilation or aneurysm. Methods This retrospective study examined the clinical and laboratory markers of patients with iKD over time, along with those of patients with complete KD (cKD) and febrile controls. Results Of 795 patients, 178 had iKD, 504 had cKD and 113 were febrile controls. During the transition from the acute to subacute phase, the age-adjusted hemoglobin levels and platelet counts were significantly lower and higher, respectively, in the subacute phase than in the acute phase in both iKD and cKD patients, which differed from those of febrile controls. Lower levels of acute and subacute age-adjusted hemoglobin levels in iKD patients (odds ratio [OR], 0.538 and 0.583; p=0.006 and 0.018, respectively) and higher subacute platelet counts in cKD patients (OR, 1.004; p=0.014) were correlated with the risk of coronary dilation. A higher acute neutrophil-to-lymphocyte ratio was associated with aneurysm only in cKD patients (OR, 1.059; p=0.044). Conclusions The iKD patients share KD-specific laboratory marker profiles in terms of complete blood cell counts and acute phase reactant levels with cKD patients. However, the factors predicting coronary dilation differ according to the phenotype; lower acute and subacute age-adjusted hemoglobin levels predict coronary dilation only in iKD patients.

BCL2L11 Is Associated With Kawasaki Disease in Intravenous Immunoglobulin Responder Patients

Kawasaki disease (KD) is a self-limited systemic vasculitis of an unknown pathogenesis mainly affecting children <5 years old. KD is a clinically heterogeneous disease; its diagnosis is based on common clinical symptoms, and there is no specific diagnostic test for it. Complete KD is diagnosed when subjects have at least 5 of the following 6 principal clinical signs: fever persisting for ≥5 days, bilateral conjunctival congestion, changes to the lips and oral cavity, polymorphous exanthema, changes to peripheral extremities, and acute nonpurulent cervical lymphadenopathy. The standard treatment for KD is high-dose intravenous immunoglobulin (IVIG), manufactured from normal human immunoglobulin purified from the full plasma of a thousand healthy donors; it reduces the duration of fever and the incidence of coronary artery abnormalities. The anti-inflammatory effects of IVIG are manifested in a wide range of pathological conditions, including immune thrombocytopenia, systemic lupus erythrematosus, Guillain–Barre syndrome, and others. Despite IVIG therapy, however, ≈15% of patients with KD have persistent or recurrent fever with a high risk for coronary artery lesions. In our KD patients data, we also observed significant differences in clinical variables between …

Impact of Flow Differentials According to Cardiac and Respiratory Cycles on Three Types of Fontan Operation

Few hemodynamic comparison studies on various types of Fontan operation have been reported. The objective of this study was to perform hemodynamic comparisons for flow size and volume in three types of Fontan operation: atriopulmonary connection (APC), lateral tunnel (LT), and extracardiac conduit (ECC). Forty patients with Fontan operation (8 with APC Fontan, 22 with LT Fontan, and 10 with ECC Fontan) were enrolled. Velocity time integral (VTI) and average peak velocity (APV) were assessed according to cardiac and respiratory cycles in SVC, IVC, hepatic vein, conduit, LPA, and RPA using direct intravenous Doppler echocardiography. During each cardiac cycle in APC, VTI and APV between inspiration and expiration did not show significant differences in SVC, IVC, HV, LPA, or RPA. During each cardiac cycle in LT and ECC, VTI and APV between inspiration and expiration showed significant differences in all native vessels. The gap between S and D wave in APC was the highest, followed by that in LT. It was the lowest in ECC regardless of inspiration or expiration. Hepatic reverse VTI and APV in APC showed significant decreases compared to those in VC and PA during inspiration and expiration. Flow size and volume in APC were more influenced by cardiac cycle. Those in LT were moderately influenced by both respiratory cycle and cardiac cycle while those in ECC were more influenced by respiratory cycle. APC Fontan has hemodynamic inefficiency with prominent reverse flow. However, total cavopulmonary connection (TCPC) Fontan has more hemodynamic efficiency without prominent reverse flows.

Clinical and laboratory profiles of hospitalized children with acute respiratory virus infection

Purpose Despite the availability of molecular methods, identification of the causative virus in children with acute respiratory infections (ARIs) has proven difficult as the same viruses are often detected in asymptomatic children. Methods Multiplex reverse transcription polymerase chain reaction assays were performed to detect 15 common respiratory viruses in children under 15 years of age who were hospitalized with ARI between January 2013 and December 2015. Viral epidemiology and clinical profiles of single virus infections were evaluated. Results Of 3,505 patients, viruses were identified in 2,424 (69.1%), with the assay revealing a single virus in 1,747 cases (49.8%). While major pathogens in single virus-positive cases differed according to age, human rhinovirus (hRV) was common in patients of all ages. Respiratory syncytial virus (RSV), influenza virus (IF), and human metapneumovirus (hMPV) were found to be seasonal pathogens, appearing from fall through winter and spring, whereas hRV and adenovirus (AdV) were detected in every season. Patients with ARIs caused by RSV and hRV were frequently afebrile and more commonly had wheezing compared with patients with other viral ARIs. Neutrophil-dominant inflammation was observed in ARIs caused by IF, AdV, and hRV, whereas lymphocyte-dominant inflammation was observed with RSV A, parainfluenza virus, and hMPV. Monocytosis was common with RSV and AdV, whereas eosinophilia was observed with hRV. Conclusion In combination with viral identification, recognition of virus-specific clinical and laboratory patterns will expand our understanding of the epidemiology of viral ARIs and help us to establish more efficient therapeutic and preventive strategies.

Chronological Echocardiographic Changes in Healthy Term Neonates within Postnatal 72 Hours Using Doppler Studies

Background This study evaluated echocardiographic changes in full-term healthy neonates during early transitional period from postnatal 0–72 hours at 12-hour intervals by echocardiography. Methods This was a prospective, observational, and longitudinal single-center cohort study. Morphometric, functional, systolic, diastolic, and tissue Doppler imaging (TDI) parameters (patent ductus arteriosus [PDA], aorta, superior vena cava [SVC], stroke volume [SV], cardiac output [CO], cardiac index [CI], early diastolic flow velocity [E], late diastolic flow velocity [A], early filling in TDI [E′], peak systolic annular velocity in TDI [S′], late velocity peak in TDI [A′], and myocardial performance index [MPI]) were evaluated in left ventricle (LV) and right ventricle (RV) with 56 newborns. Results Sizes and peak velocities of PDA before postnatal 24 hours were significantly changed than those after postnatal 24 hours. Aortic velocity time integral (VTI), systolic blood pressure (BP), LV SV/kg, LV CO/kg, LV CI, and SVC flow/LV CO before 24 hours showed significantly changes than those after 24 hours. Also, LV and RV MPI before 24 hours were significantly higher than those after 24 hours. LV E/E′ was significantly higher than RV E/E′. Conclusion Postnatal 24 hours is critical time for hemodynamic closure of PDA because aortic VTI, systolic BP, LV SV, LV CO, LV CI, and SVC flow/LV CO showed simultaneously significant changes after 24 hours at the same time as 24 hours of physiological closure of PDA. Chronological and dramatic changes of systolic, diastolic, and TDI parameters during early postnatal period can be used to compile normal baseline data of healthy full-term neonates.