Prenatal metal levels and congenital anomalies of the kidney and urinary tract: The Japan Environment and Children's Study.

BACKGROUND: Prenatal exposure to metal elements has been reported as a potential risk factor for congenital malformation. However, studies on the relationship with congenital anomalies of the kidney and urinary tract (CAKUT) are very scarce. METHODS: Participants of a prospective cohort from the Japan Environment and Children's Study, conducted at 15 research centers, were recruited between January 2011 and March 2014. The exposure factors were concentrations of lead (Pb), cadmium (Cd), mercury (Hg), selenium (Se), and manganese (Mn) measured from maternal whole blood in the second or third trimester. The primary outcome was CAKUT diagnosed during the first three years of life, which was classified into isolated cases and complicated cases accompanied by extrarenal congenital defects. To conduct a nested case-control design within the cohort, we selected 351 isolated cases with 1404 matched controls, and 79 complicated cases with 316 matched controls. RESULTS: A logistic regression model was used to examine the associations between individual metal concentrations and each subtype of CAKUT. A higher level of Se was associated with an increased risk of isolated CAKUT (adjusted odds ratio [95 % confidence interval]: 3.22 [1.33-7.77]). Meanwhile, higher levels of Pb and Mn were associated with a reduced risk of the complicated subtype (0.46 [0.24-0.90] and 0.33 [0.15-0.73], respectively). A Bayesian kernel machine regression model accounting for mixed effects of multiple metals further demonstrated that a higher level of Mn alone was significantly associated with a reduced occurrence of the complicated subtype. CONCLUSIONS: Using a stringent statistical approach, the present study demonstrated that a higher Mn concentration in the maternal blood was associated with a lower risk of complicated CAKUT in offspring. Further cohort and experimental studies are needed to verify the clinical impact of this finding.

Expression of hypothalamic feeding-related peptide genes and neuroendocrine responses in an experimental allergic encephalomyelitis rat model.

Experimental allergic encephalomyelitis (EAE) is considered to be a useful animal model of human multiple sclerosis (MS). However, among the various symptoms of MS, the mechanisms contributing to inflammatory anorexia remain unclear. In the present study, we used an EAE rat model to examine changes in expression levels of hypothalamic feeding-related peptide genes and neuroendocrine responses such as the hypothalamo-neurohypophysial system and the hypothalamo-pituitary-adrenal (HPA) axis. The weight gain and cumulative food intake in EAE rats in the early days after immunization was significantly lower than that of the control group. The expression of orexigenic peptide genes Npy and Agrp were significantly increased, whereas the levels of anorectic peptide genes (Pomc and Cart) were significantly decreased in the hypothalamus of EAE rats. There was also a significant increase in the mRNA and plasma oxytocin (OXT) but not of arginine vasopressin (AVP) in the supraoptic and paraventricular nuclei (PVN) of EAE rats at days 12 and 18 after immunization. The expression of corticotropin-releasing hormone (Crh) and Avp was downregulated and upregulated, respectively, in the parvocellular division of the PVN at day 12 after immunization. The expression level of Pomc in the anterior pituitary significantly increased, accompanied by increased plasma corticosterone levels, at days 6, 12, and 18 after immunization. These results suggest that inflammatory anorexia in rat EAE may be caused by activation of the OXT-ergic pathway and HPA axis via changes in the expression of hypothalamic feeding-related peptides, including Avp but not Crh.

Associations between metal concentrations in whole blood and placenta previa and placenta accreta: the Japan Environment and Children's Study (JECS).

BACKGROUND: Placenta previa and placenta accreta associate with high morbidity and mortality for both mothers and fetus. Metal exposure may have relationships with placenta previa and placenta accreta. This study analyzed the associations between maternal metal (cadmium [Cd], lead [Pb], mercury [Hg], selenium [Se], and manganese [Mn]) concentrations and placenta previa and placenta accreta. METHODS: We recruited 17,414 women with singleton pregnancies. Data from a self-administered questionnaire regarding the first trimester and medical records after delivery were analyzed. Maternal blood samples were collected to measure metal concentrations. The subjects were classified into four quartiles (Q1, Q2, Q3, and Q4) according to metal concentrations. RESULTS: The odds ratio for placenta previa was significantly higher among subjects with Q4 Cd than those with Q1 Cd. The odds ratio for placenta previa was significantly higher for subjects with Q2 Pb than those with Q1 Pb. CONCLUSION: Participants with placenta previa had higher Cd concentrations. However, this study was cross-sectional and lacked important information related to Cd concentration, such as detailed smoking habits and sources of Cd intake. In addition, the subjects in this study comprised ordinary pregnant Japanese women, and it was impossible to observe the relationship between a wide range of Cd exposure and placenta previa. Therefore, epidemiological and experimental studies are warranted to verify the relationship between Cd exposure and pregnancy abnormalities.

Chronic mandibular osteomyelitis caused by Granulicatella adiacens in an immunocompetent child.

We report a pediatric case aged 10 years with Granulicatella adiacens-associated chronic mandibular osteomyelitis. The causative pathogen was uncertain because polymicrobial species were detected from the bacterial culture in bone marrow fluid. In contrast, G. adiacens was predominantly identified in the clone library analysis of the bacterial 16S rRNA gene sequence. Vancomycin to which G. adiacens was reported to be susceptible was not administrated sufficiently to this patient because of its adverse event, whereas linezolid and ciprofloxacin was alternatively effective for the treatment of chronic mandibular osteomyelitis.

Centrally administered kisspeptin suppresses feeding via nesfatin-1 and oxytocin in male rats.

Kisspeptin (KP), known as a hypothalamic neuropeptide, plays a critical role in the regulation of not only reproduction but also food intake. The anorectic neuropeptides, nesfatin-1 and oxytocin (OXT), are expressed in central nervous system, particulaly in various hypothalamic nuclei, and peripheral tissue. We examined the effects of the intracerebroventricular (icv) administration of KP-10 on feeding and nesfatin-1-immunoreactive (ir) or OXT-ir neurons in the rat hypothalamus, using Fos double immunohistochemistry in male rats. Cumulative food intake was remarkably decreased 0.5-3 h after icv administration of KP-10 (6.0 µg) compared to the vehicle treated and the KP-10 (3.8 µg) treated group. The icv administration of KP-10 significantly increased the number of nesfatin-1-ir neurons expressing Fos in the supraoptic nucleus (SON), paraventricular nucleus (PVN), arcuate nucleus (ARC), dorsal raphe nucleus, locus coeruleus, and nucleus tractus solitarius. The decreased food intake induced by KP-10 was significantly attenuated by pretreatment with the icv administration of antisense RNA against nucleobindin-2. After icv administration of KP-10, the percentages of OXT-ir neurons expressing FOS were remarkably higher in the SON and PVN than for vehicle treatment. The KP-10-induced anorexia was partially abolished by pretreatment with OXT receptor antagonist (OXTR-A). The percentage of nesfatin-1-ir neurons expressing Fos-ir in the ARC was also decreased by OXTR-A pretreatment. These results indicate that central administration of KP-10 activates nesfatin-1- and OXT neurons, and may play an important role in the suppression of feeding in male rats.

Involvement of central nesfatin-1 neurons on oxytocin-induced feeding suppression in rats.

Peripheral anorectic hormones, such as peptide YY (PYY) and oxytocin (OXT), suppress food intake. A newly identified anorectic neuropeptide, nesfatin-1, is synthesized in both peripheral tissue and the central nervous system, particularly by various nuclei in the hypothalamus and brainstem. Here, we examined the effects of intraperitoneal (ip) administration of PYY3-36, OXT, and OXT analog, on nesfatin-1-immunoreactive (ir) neurons in the rat hypothalamus and brainstem, using Fos double fluorescence-immunohistochemistry. The ip administration of OXT and OXT analog significantly increased the number of nesfatin-1-ir neurons expressing Fos-ir in the paraventricular nucleus, the arcuate nucleus, and the nucleus tractus solitarius, but not in the supraoptic nucleus, the lateral hypothalamic area, and the area postrema. No differences in the percentage of nesfatin-1-ir neurons expressing Fos in the nuclei of the hypothalamus and brainstem were observed, between rats treated with vehicle or those treated with PYY3-36. The decreased food intake, induced by OXT and OXT analog, was attenuated significantly by pretreatment with intracerebroventricular administration of antisense nesfatin-1. These results suggested that nesfatin-1-expressing neurons in the hypothalamus and brainstem may play a role in sensing the peripheral level of OXT and its suppression of feeding in rats.