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1.
Amino Acids ; 56(1): 38, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844708

RESUMO

Biomarkers that accurately reflect renal function are essential in management of chronic kidney diseases (CKD). However, in children, age/physique and medication often alter established renal biomarkers. We studied whether amino acid enantiomers in body fluids correlate with renal function and whether they are influenced by physique or steroid medication during development. We conducted a prospective study of children 2 to 18 years old with and without CKD. We analyzed associations of serine/asparagine enantiomers in body fluids with major biochemical parameters as well as physique. To study consequences of kidney dysfunction and steroids on serine/asparagine enantiomers, we generated juvenile mice with uninephrectomy, ischemic reperfusion injury, or dexamethasone treatment. We obtained samples from 27 children, of which 12 had CKD due to congenital (n = 7) and perinatal (n = 5) causes. Plasma D-asparagine and the D/L-serine ratio had robust, positive linear associations with serum creatinine and cystatin C, and detected CKD with high sensitivity and specificity, uninfluenced by body size or biochemical parameters. In the animal study, kidney dysfunction increased plasma D-asparagine and the D/L-serine ratio, but dexamethasone treatment did not. Thus, plasma D-asparagine and the D/L-serine ratio can be useful markers for renal function in children.


Assuntos
Asparagina , Biomarcadores , Insuficiência Renal Crônica , Serina , Criança , Animais , Humanos , Asparagina/sangue , Asparagina/metabolismo , Insuficiência Renal Crônica/sangue , Pré-Escolar , Serina/sangue , Camundongos , Masculino , Feminino , Adolescente , Biomarcadores/sangue , Estudos Prospectivos , Dexametasona , Estereoisomerismo , Creatinina/sangue , Rim/metabolismo
3.
Proc Natl Acad Sci U S A ; 120(15): e2300817120, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37014864

RESUMO

Mammals exhibit systemic homochirality of amino acids in L-configurations. While ribosomal protein synthesis requires rigorous chiral selection for L-amino acids, both endogenous and microbial enzymes convert diverse L-amino acids to D-configurations in mammals. However, it is not clear how mammals manage such diverse D-enantiomers. Here, we show that mammals sustain systemic stereo dominance of L-amino acids through both enzymatic degradation and excretion of D-amino acids. Multidimensional high performance liquidchromatography analyses revealed that in blood, humans and mice maintain D-amino acids at less than several percent of the corresponding L-enantiomers, while D-amino acids comprise ten to fifty percent of the L-enantiomers in urine and feces. Germ-free experiments showed that vast majority of D-amino acids, except for D-serine, detected in mice are of microbial origin. Experiments involving mice that lack enzymatic activity to catabolize D-amino acids showed that catabolism is central to the elimination of diverse microbial D-amino acids, whereas excretion into urine is of minor importance under physiological conditions. Such active regulation of amino acid homochirality depends on maternal catabolism during the prenatal period, which switches developmentally to juvenile catabolism along with the growth of symbiotic microbes after birth. Thus, microbial symbiosis largely disturbs homochirality of amino acids in mice, whereas active host catabolism of microbial D-amino acids maintains systemic predominance of L-amino acids. Our findings provide fundamental insight into how the chiral balance of amino acids is governed in mammals and further expand the understanding of interdomain molecular homeostasis in host-microbial symbiosis.


Assuntos
Aminoácidos , Simbiose , Humanos , Animais , Camundongos , Aminoácidos/química , Serina , Biossíntese de Proteínas , Estereoisomerismo , Mamíferos
4.
Int J Urol ; 30(4): 408-414, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36702789

RESUMO

OBJECTIVES: The aim of this study was to compare the demographic characteristics of school-aged children with nocturnal enuresis and factors influencing hospital visits between two regions in Japan. METHODS: A cross-sectional survey was conducted in Hirakata City, Osaka Prefecture, and Urayasu City, Chiba Prefecture. An anonymous online questionnaire was administered to all public elementary and junior high school students (aged 6-16 years) or their guardians. Questions included age, gender, perinatal history, frequency of nocturnal enuresis, frequency of bowel movements, comorbidities, and hospital visits for nocturnal enuresis. RESULTS: The survey response rates were 15.4% in Hirakata City and 37.0% in Urayasu City. In total, 426 children with nocturnal enuresis in Hirakata City and 270 in Urayasu City were included in the final analysis. In both cities, the boy-girl ratio was approximately 2:1, and the prevalence of nocturnal enuresis gradually decreased with age. Multivariate analysis revealed that children aged ≥11 years had a significantly higher proportion of hospital visits (OR, 2.61; 95% CI: 1.49-4.56; p = 0.001; OR, 2.72; 95% CI: 1.12-6.64; p = 0.027, respectively). However, the frequency of nocturnal enuresis did not affect hospital visits. CONCLUSIONS: The findings of this study suggest that parents with school-aged children have low awareness that nocturnal enuresis is a health problem and therefore subject to medical consultation. Although the proportion of hospital visits increases for children aged ≥11 years, children and families suffering from nocturnal enuresis should be encouraged to see a doctor instead of adopting a "wait and see attitude," even at a young age.


Assuntos
Enurese Noturna , Criança , Feminino , Humanos , Masculino , Estudos de Coortes , Estudos Transversais , Enurese , Hospitais , Japão/epidemiologia , Enurese Noturna/epidemiologia , Enurese Noturna/terapia , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adolescente
5.
Nutrients ; 14(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36432628

RESUMO

We evaluated the relationship between fetal growth in preterm babies using the head circumference (HC)/chest circumference (CC) ratio and other anthropometric parameters at birth and at school age. Data were collected from 187 very low birth weight (VLBW) children born at less than 30 weeks of gestational age (GA) at birth and at 6 years. We assessed the correlation between the HC/CC ratio and body weight (BW), body length (BL), and HC z-scores at birth, and BW, body height (BH), and body mass index (BMI) z-scores at 6 years. Multiple regression analysis showed that BW z-score, BL z-score, and HC z-score at birth were significantly associated with HC/CC at birth. The BMI z-score at 6 years was also significantly associated with HC/CC at birth. The HC/CC ratio at birth is a reliable parameter for evaluating fetal growth restriction and a possible predictor of physical growth in VLBW children.


Assuntos
Retardo do Crescimento Fetal , Recém-Nascido Prematuro , Lactente , Criança , Feminino , Recém-Nascido , Humanos , Retardo do Crescimento Fetal/diagnóstico , Recém-Nascido de muito Baixo Peso , Estatura , Idade Gestacional
6.
Pediatr Int ; 64(1): e15230, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35789030

RESUMO

The concept of the developmental origins of health and disease (DOHaD) views unfavorable perinatal circumstances as contributing to the development of diseases in later life. It is well known that such unfavorable circumstances play an important role as a risk factor for chronic kidney disease (CKD) in infants born with prematurity. Low birthweight (LBW) is believed to be a potential contributor to CKD in adulthood. Preterm and/or LBW infants are born with incomplete nephrogenesis. As a result, the number of nephrons is low. The poor intrauterine environment also causes epigenetic changes that adversely affect postnatal renal function. After birth, hyperfiltration of individual nephrons due to low nephron numbers causes proteinuria and secondary glomerulosclerosis. Furthermore, the risk of CKD increases as renal damage takes a second hit from exposure to nephrotoxic substances and acquired insults such as acute kidney injury after birth among infants in neonatal intensive care. Meanwhile, unfortunately, recent studies have shown that the number of nephrons in healthy Japanese individuals is approximately two-thirds lower than that in previous reports. This means that Japanese premature infants are clearly at a high risk of developing CKD in later life. Recently, several DOHaD-related CKD studies from Japanese researchers have been reported. Here, we summarize the relevance of CKD in conjunction with DOHaD and review recent studies that have examined the impact of the upward LBW trend in Japan on renal health.


Assuntos
Injúria Renal Aguda , Insuficiência Renal Crônica , Adulto , Feminino , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Rim , Gravidez , Proteinúria , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia
7.
FEBS Lett ; 596(22): 2889-2897, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35665501

RESUMO

d-Serine modulates excitatory neurotransmission by binding to N-methyl-d-aspartate glutamate receptors. d-Amino acid oxidase (DAO) degrades d-amino acids, such as d-serine, in the central nervous system, and is associated with neurological and psychiatric disorders. However, cell types that express brain DAO remain controversial, and whether brain DAO influences systemic d-amino acids in addition to brain d-serine remains unclear. Here, we created astrocyte-specific DAO-conditional knockout mice. Knockout in glial fibrillary acidic protein-positive cells eliminated DAO expression in the hindbrain and increased d-serine levels significantly in the cerebellum. Brain DAO did not influence levels of d-amino acids in the forebrain or periphery. These results show that astrocytic DAO regulates d-serine specifically in the hindbrain.


Assuntos
D-Aminoácido Oxidase , Serina , Animais , Camundongos , Serina/metabolismo , D-Aminoácido Oxidase/genética , D-Aminoácido Oxidase/metabolismo , Astrócitos/metabolismo , Camundongos Knockout , Aminoácidos , Cerebelo/metabolismo
8.
Paediatr Int Child Health ; 42(2): 72-77, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35588163

RESUMO

INTRODUCTION: Early diagnosis of tuberculosis (TB) in infants is important but is commonly missed because the symptoms are often non-specific. CASE PRESENTATION: A Nepalese male infant born at 26 weeks gestation and weighing 1227 g (97th centile) was admitted to the neonatal intensive care unit (NICU) immediately after birth for the management of his prematurity. After extubation on Day 8, his oxygen saturation became unstable and he required nasal continuous positive airway pressure with oxygen for 3 months. On Day 104, further detailed evaluation was required because there was no improvement in his respiratory condition. A computed tomography (CT) scan demonstrated scattered miliary nodules in both lung fields. Acid-fast staining for the mycobacteria and TB polymerase chain reaction (PCR) of the sputum obtained directly by laryngeal aspiration confirmed Mycobacterium tuberculosis. On Day 105, he was therefore transferred to a tertiary care hospital for further intensive care. Pathology findings suggested placental involvement with TB owing to chronic endometrial infection. In addition, a maternal abdominal CT scan demonstrated bilateral calcified lesions in the ovaries. He completed antituberculous chemotherapy and was discharged 3 months later. At 18 months of age there are no sequelae and his development is almost normal. None of the infants or medical personnel who were exposed in the NICU developed secondary TB. CONCLUSION: In neonates with persistent respiratory distress, neonatologists should consider TB infection as a differential diagnosis. ABBREVIATIONS: CLD: chronic lung disease; CRP: C-reactive protein; CT: computed tomography; IGRA: interferon-γ release assay; IVF-ET: in vitro fertilisation-embryo transfer; N-CPAP: nasal continuous positive airway pressure; NICU: neonatal intensive care unit; PCR: polymerase chain reaction; PROM: premature rupture of membranes; TB: tuberculosis; WBC: white blood cells.


Assuntos
Doenças do Recém-Nascido , Pneumopatias , Tuberculose Miliar , Tuberculose Pulmonar , Proteína C-Reativa , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/terapia , Masculino , Mães , Ovário , Oxigênio/uso terapêutico , Placenta , Gravidez , Tuberculose Miliar/complicações , Tuberculose Miliar/diagnóstico , Tuberculose Miliar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia
9.
J Clin Med ; 11(5)2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35268509

RESUMO

We aimed to determine the differences in the growth trajectories of the youngest gestational survivors (<25 weeks' gestation) up to 6 years of age compared to those of older gestational ages. Preterm infants were divided into two groups: 22−24 weeks' gestation (male (M) 16, female (F) 28) and 25−29 weeks' gestation (M 84, F 59). Z-scores of body weight (BW), body length (BL), and body mass index (BMI) were derived from Japanese standards at 1, 1.5, 3, and 6 years of corrected age. Comparisons between the two groups by sex were made using the Wilcoxon test and linear regression analysis to examine the longitudinal and time-point associations of anthropometric z-scores, the presence of small for gestational age (SGA), and the two gestational groups. BW, BL, BMI, and z-scores were significantly lower in the 22−24 weeks group at almost all assessment points. However, there were no significant differences in BW, BL, BMI, and z-scores between the two female groups after 3 years. BMI z-scores were significantly associated with the youngest gestational age and the presence of SGA at all ages in males, but not in females. The youngest gestational age had a greater influence in males on the z-score of anthropometric parameters up to 6 years of age.

11.
Pediatr Int ; 64(1): e15049, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34747553

RESUMO

BACKGROUND: This study aimed to evaluate the quality and reliability of Japanese YouTube videos pertaining to nocturnal enuresis (NE). METHODS: In this cross-sectional study, we performed a YouTube search using the keyword "Ya-nyou-shou" ('nocturnal enuresis' in Japanese). We considered the first 200 videos listed based on the YouTube default option. Videos that were irrelevant, concerned personal experiences or adult NE, had non-Japanese content, were advertisements, were duplicated, and those without audio were excluded. Video features and upload source were recorded. The Modified DISCERN, Journal of the American Medical Association (JAMA), and Global Quality Scale (GQS) scoring systems were used for analysis. Two independent pediatricians, specialists in nephrology and urology, completed the scoring. Correlation analysis was performed between video features and the three quality analysis scores. RESULTS: In total, 72 videos were analyzed. The most common upload sources were physicians (40.3%) and non-physician health personnel (40.3%). The median modified DISCERN, JAMA, and GQS scores for the videos were 1 (lowest: 0; highest: 4), 2 (lowest: 1; highest: 3), and 2 (lowest: 1; highest: 4), respectively. The highest scores for video power index (VPI) were for independent users (6.43 points) and physicians (3.05 points). There were positive correlations between the VPI and video length and modified DISCERN and GQS scores. No video presenter disclosed conflicts of interest. CONCLUSIONS: Most Japanese YouTube videos about NE were low quality. Healthcare experts should be encouraged to upload better quality content.


Assuntos
Enurese , Mídias Sociais , Estudos Transversais , Humanos , Disseminação de Informação , Reprodutibilidade dos Testes , Estados Unidos , Gravação em Vídeo
12.
Pediatr Int ; 64(1): e14844, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33999477

RESUMO

BACKGROUND: Little is known about the relationship between fetal growth and size at school age in children born prematurely. We evaluated the relationships between gestational age and anthropometric z-scores at birth and size at 6 years of age in very-low-birthweight infants born at <30 weeks' gestation. METHODS: We collected data from the medical records of 187 preterm children at birth and 6 years of age. We evaluated correlations between gestational age and z-scores for weight, body length, and head circumference at birth and z-scores for weight, height, and body mass index at 6 years of age. RESULTS: Simple regression analysis showed that, in boys and the overall group, gestational age and z-scores for weight, body length, and head circumference at birth had significant association with z-scores for weight, height, and body mass index at 6 years of age. No significant associations were found in girls, except for weight z-scores at 6 years with gestational age and head circumference z-scores at birth. Multiple regression analysis showed that gestational age and length z-score at birth were significantly and independently associated with weight and height z-score at 6 years. Gestational age was also significantly and independently associated with body mass index z-score at 6 years. CONCLUSION: Gestational age and fetal growth in length (assessed with the birth-length z-score) were associated with anthropometric z-scores at 6 years in very-low-birthweight children born at <30 weeks of gestation, especially in boys.


Assuntos
Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Lactente , Masculino , Criança , Feminino , Recém-Nascido , Humanos , Peso ao Nascer , Estudos Retrospectivos , Índice de Massa Corporal , Idade Gestacional , Recém-Nascido Pequeno para a Idade Gestacional
13.
Pediatr Res ; 91(7): 1695-1702, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34365467

RESUMO

BACKGROUND: Congenital obstructive nephropathy (CKD) is commonly implicated in the pathophysiology of chronic kidney disease occurring in the pediatric and adolescent age groups and the release of reactive oxygen species contribute to the worsening of renal fibrosis. Molecular hydrogen (H2) protects against tissue injury by reducing oxidative stress. We evaluated the efficacy of oral H2-rich water (HW) intake in preventing unilateral ureteral obstruction (UUO)-induced renal injury in rats. METHODS: Male Sprague-Dawley UUO or control rats were administered with distilled water (DW) or HW for 2 weeks post-surgery. Histopathological and immunohistochemical analyses of kidney samples were performed. RESULTS: Histological changes were not apparent in the sham-operated kidneys. However, UUO kidneys were found to have widened interstitial spaces and tubular dilatation. Compared with the UUO + DW group, HW administration attenuated tubulointerstitial injury and reduced interstitial fibrotic area, causing a substantial decline in the frequency of α-SMA-, ED-1-, and TGF-ß1-positive cells in the UUO + HW group. The decrease in the klotho mRNA expression in the UUO + HW group was less pronounced than that in the UUO + DW group. CONCLUSION: Oral HW intake reduced oxidative stress and prevented interstitial fibrosis in UUO kidneys, potentially involving klotho in the underlying mechanism. IMPACT: Oral intake of hydrogen-rich water (HW) can reduce oxidative stress and suppress interstitial fibrosis in unilateral ureteral obstruction-induced renal injury in rats. This mechanism possibly involves klotho, which is known for its antiaging roles. The association between molecular hydrogen and klotho in renal fibrosis is well known; this is the first report on the association in a unilateral ureteral obstruction model. Drinking HW is a safe and convenient treatment for oxidative stress-induced pathologies, without side effects. As a prospect for future research, oral HW intake to treat oxidative stress may improve renal fibrosis in congenital obstructive nephropathy.


Assuntos
Nefropatias , Insuficiência Renal Crônica , Obstrução Ureteral , Adolescente , Animais , Fibrose , Humanos , Hidrogênio/metabolismo , Hidrogênio/farmacologia , Hidrogênio/uso terapêutico , Rim/metabolismo , Nefropatias/patologia , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Obstrução Ureteral/complicações , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/metabolismo , Água
14.
Juntendo Iji Zasshi ; 68(3): 235-241, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-39021721

RESUMO

Objectives: This study aimed to investigate the protective effects of hydrogen-rich water (HW) intake on renal injury in neonatal rats with high oxygen loading. Materials: We used pregnant and newborn Sprague-Dawley rats. Methods: Four groups were set up, with mother and newborn rats immediately after delivery as one group: RA-PW (room air and purified water), RA-HW (room air and HW), O2-PW (80% oxygen and purified water), and O2-HW (80% oxygen and HW). The newborn rats were maintained in either a normoxic (room air, 21% oxygen) or controlled hyperoxic (80% oxygen) environment from birth. Then, HW (O2-HW and RA-HW groups) or PW (O2-PW and RA-PW groups) was administered to parents of each group. Results: The number of immature glomeruli significantly increased in the O2-PW group (exposed to hyperoxia). Conversely, the O2-HW group had significantly fewer immature glomeruli than O2-PW group. In the RT-PCR analysis of kidney tissue, α-SMA, TGF-ß, and TNF-α levels were significantly higher in the O2-PW group than in the RA-PW group and significantly lower in the O2-HW group than in the O2-PW group. Conclusions: HW intake can potentially reduce oxidative stress and prevent renal injury in neonates with high oxygen loading.

17.
Pediatr Int ; 63(11): 1339-1343, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33930226

RESUMO

BACKGROUND: The purpose of this study was to assess whether enuretic Japanese patients with nocturnal polyuria (NP) who met Hoashi's criteria (6-9 years: ≥200 mL; 10 years and older: ≥250 mL) met the International Children's Continence Society (ICCS; expected bladder capacity × 130%) and Rittig's criteria for nocturnal polyuria (>[age+9] × 20 mL). We also compared the effectiveness of 1-desamino-8-d-arginine vasopressin (DDAVP) with the three criteria. METHODS: Fifty-four patients who had NP with normal bladder capacity were enrolled: 36 boys (67%); median age, 8 (interquartile range: 7-9). We compared the diagnostic differences between the Hoashi's criteria and international standards (ICCS and Rittig's) for NP and the short-term effects of DDAVP. The patients received DDAVP for 8 weeks; we evaluated the association between each evaluation method and the effects of therapy. RESULTS: Only 17% of the patients met both Hoashi's and ICCS criteria, whereas 26% met both Hoashi's and Rittig's criteria. The therapeutic effect of DDAVP did not differ significantly between these two groups: there was an effective rate of 73% (Hoashi's criteria) versus 50% (ICCS criteria), P = 0.19, and an effective rate of 71% (Hoashi's criteria) versus 62% (Rittig's criteria), P = 0.84. CONCLUSIONS: Hoashi's criteria are widely used but, according to both the ICCS and Rittig's criteria, approximately 80% of the patients did not fulfill the definition of NP. However, 8 weeks after the DDAVP treatment began, no significant difference was observed in the therapeutic effect of DDAVP according to each set of criteria. The definition of NP should account for the physical disparities between Japanese people and Westerners.


Assuntos
Enurese Noturna , Arginina Vasopressina , Criança , Desamino Arginina Vasopressina/uso terapêutico , Humanos , Japão/epidemiologia , Masculino , Enurese Noturna/diagnóstico , Enurese Noturna/tratamento farmacológico , Poliúria/diagnóstico , Poliúria/tratamento farmacológico
18.
Tohoku J Exp Med ; 253(4): 275-281, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33896891

RESUMO

Sepsis and septic shock are associated with high mortality and neurodevelopmental impairment in preterm infants. Recently, endotoxin and mediator removal using a polymyxin B-immobilized fiber column for direct hemoperfusion (PMX-DHP) has been used for the management of septic shock even in neonates. Although early withdrawal from shock with PMX-DHP contributes to survival, its effect on neurodevelopment after discharge is unclear. This study aimed to examine short-term neurodevelopmental impairment in preterm infants with septic shock who were treated with PMX-DHP. We retrospectively assessed five infants who received treatment with PMX-DHP (median 25.5 [interquartile range: 24.8-28.3] weeks and 817 [interquartile range: 667-954] g). Neurodevelopmental outcomes were assessed with the Kyoto Scale of Psychological Development 2001 at a median 34.5 (interquartile range: 29.5-44.5) months of corrected age after discharge. The short-term neurodevelopmental prognosis of preterm infants treated with PMX-DHP for septic shock was delayed (overall developmental quotient < 70) with an average quotient of 57.3. Furthermore, four (80%) of five patients presented with intraventricular hemorrhage and another four (80%) with periventricular leukomalacia. In conclusion, preterm infants with septic shock treated with PMX-DHP had unsatisfactory short-term neurodevelopmental outcomes. Hence, the effect of PMX-DHP in improving neurodevelopmental prognosis even in preterm infants with septic shock should be further evaluated.


Assuntos
Hemoperfusão , Sistema Nervoso/crescimento & desenvolvimento , Polimixina B/uso terapêutico , Choque Séptico/terapia , Adulto , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Choque Séptico/complicações , Choque Séptico/psicologia
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