Analysis of Cytokine Profiles in Pediatric Myocarditis Multicenter Study.

Acute myocarditis (AM) is an inflammatory disease of the heart muscle that can progress to fulminant myocarditis (FM), a severe and life-threatening condition. The cytokine profile of myocarditis in children, especially in relation to fulminant myocarditis, is not well understood. This study aims to evaluate the cytokine profiles of acute and fulminant myocarditis in children. Pediatric patients diagnosed with myocarditis were included in the study. Cytokine levels were measured using a multiplexed fluorescent bead-based immunoassay. Statistical analysis was performed to compare patient characteristics and cytokine levels between FM, AM, and healthy control (HC) groups. Principal component analysis (PCA) was applied to cytokine groups that were independent among the FM, AM, and HC groups. The study included 22 patients with FM and 14 with AM patients. We identified four cytokines that were significantly higher in the FM group compared to the AM group: IL1-RA (p = 0.002), IL-8 (p = 0.005), IL-10 (p = 0.011), and IL-15 (p = 0.005). IL-4 was significantly higher in the AM group compared to FM and HC groups (p = 0.006 and 0.0015). PDGF-AA, and VEGF-A were significantly lower in the FM group than in the AM group (p = 0.013 and <0.001). Similar results were obtained in PCA. Cytokine profiles might be used to differentiate pediatric FM from AM, stratify severity, and predict prognosis. The targeted therapy that works individual cytokines might provide a potential treatment for reducing the onset of the FM and calming the condition, and further studies are needed.

Histopathological findings of pericarditis in a patient with multisystem inflammatory syndrome in children associated with COVID-19: A case report.

Multisystem inflammatory syndrome in children (MIS-C), which is associated with the novel coronavirus disease 2019 (COVID-19), has been described as an inflammatory complication of exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It carries a risk of serious and lethal complications, including cardiogenic shock. Here, we report the pathological findings of the pericardium in a 10-year-old child with MIS-C, who developed pericarditis-induced cardiac tamponade. In the patient's pericardium, the numbers of infiltrating CD68+ macrophages; CD3+ , CD4+ , and CD8+ T cells; and myeloperoxidase+ granulocytes were increased, although the number of CD20+ B cells was not. These findings provide a clue to understanding the pathophysiology of MIS-C.

[Three-dimensional Quantitative Evaluation Method in 123I-MIBG Myocardial SPECT-CT].

PURPOSE: To distinguish neurodegenerative diseases using 123I-metaiodobenzylguanidine (MIBG). This study proposes a method to evaluate myocardial standardized uptake value (SUV) and assess its accuracy. METHODS: We created a 17-segment polar map of the myocardial region from single-photon emission computed tomography-computed tomography (SPECT-CT) images using a cardioliver phantom simulating the standard uptake of MIBG. We clarified the optimal reconstruction conditions with good repeatability and accuracy of quantitative values and compared them with the H/M ratio. Myocardial SUVs were evaluated from eight normal cases using our method established from the phantom experiment and compared with the H/M ratio. RESULTS: The optimal numbers of iterations and subsets in OSEM reconstruction were both 10. The optimal full width at half maximum (FWHM) value of the Gaussian filter was 4 pixels. The RCs and %CV of (1) maximum SUVmax (MaxSUVmax) and (2) average SUVmax (AveSUVmax) were (1) 36.5% and 4.99%, and (2) 33.6% and 4.84%, respectively. The RC and %CV of the H/M ratio was 15.0% and 1.50%, respectively. In clinical cases, average MaxSUVmax and AveSUVmax were 8.27 and 7.58, respectively. CONCLUSION: Myocardial SUV can provide quantitative values slightly closer to theoretical values than the H/M ratios. Besides, using the optimal reconstruction parameters makes it feasible to quantitatively assess myocardial uptake with good repeatability.

Design of a prospective multicenter randomized controlled trial evaluating the effects of gastric lavage on coffee-ground emesis in neonates: study protocol.

Neonates who swallow a considerable amount of maternal blood may exhibit vomiting and suckling disorder during the first few days of the postnatal period. Some clinicians treat these neonates with gastric lavage (GL) to prevent vomiting and the establishment of enteral feeding empirically, but there was no study assessing the effect of GL for neonates with coffee-ground emesis. We designed a multicenter randomized controlled trial to evaluate the efficacy and safety of GL in neonates with coffee-ground emesis. Vigorous neonates with birth weight ranging from 2500 g to 3999 g and gestational age between 37w0d and 41w6d who presented with coffee-ground emesis on more than twice and diagnosed as false melena, were divided into two groups using computerized randomization. We defined feeding intolerance (FI) as (1) ≥2 vomiting episodes in 4h or ≥3 episodes in 24h and/or (2) feeding failure on at least two occasions because of retching or poor sucking. Primary outcome is percentage of infants who present FI within 24 hours from admission. We also assessed the residual volumes, number of vomiting episodes, percentage of weight reduction at postnatal day 4, rates of body weight gain at 1 month of age, and peak serum total bilirubin value before discharge. To our knowledge, this is the first study to evaluate the safety and efficacy of GL for neonates with coffee-ground emesis. This trial is registered at UMIN Clinical Trials Registry as UMIN000026483.

Wnt and Shh signals regulate neural stem cell proliferation and differentiation in the optic tectum of adult zebrafish.

Adult neurogenesis occurs more commonly in teleosts, represented by zebrafish, than in mammals. Zebrafish is therefore considered a suitable model to study adult neurogenesis, for which the regulatory molecular mechanisms remain little known. Our previous study revealed that neuroepithelial-like neural stem cells (NSCs) are located at the edge of the dorsomedial region. We also showed that Notch signaling inhibits NSC proliferation in this region. In the present study, we reported the expression of Wnt and Shh signaling components in this region of the optic tectum. Moreover, inhibitors of Wnt and Shh signaling suppressed NSC proliferation, suggesting that these pathways promote NSC proliferation. Shh is particularly required for maintaining Sox2-positive NSCs. Our experimental data also indicate the involvement of these signaling pathways in neural differentiation from NSCs. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1206-1220, 2017.

Mice deficient for glucagon gene-derived peptides display normoglycemia and hyperplasia of islet {alpha}-cells but not of intestinal L-cells.

Multiple bioactive peptides, including glucagon, glucagon-like peptide-1 (GLP-1), and GLP-2, are derived from the glucagon gene (Gcg). In the present study, we disrupted Gcg by introduction of GFP cDNA and established a knock-in mouse line. Gcg(gfp/gfp) mice that lack most, if not all, of Gcg-derived peptides were born in an expected Mendelian ratio without gross abnormalities. Gcg(gfp/gfp) mice showed lower blood glucose levels at 2 wk of age, but those in adult Gcg(gfp/gfp) mice were not significantly different from those in Gcg(+/+) and Gcg(gfp/+) mice, even after starvation for 16 h. Serum insulin levels in Gcg(gfp/gfp) mice were lower than in Gcg(+/+) and Gcg(gfp/+) on ad libitum feeding, but no significant differences were observed on starvation. Islet alpha-cells and intestinal L-cells were readily visualized in Gcg(gfp/gfp) and Gcg(gfp/+) mice under fluorescence. The Gcg(gfp/gfp) postnatally developed hyperplasia of islet alpha-cells, whereas the population of intestinal L-cells was not increased. In the Gcg(gfp/gfp), expression of Aristaless-related homeobox (Arx) was markedly increased in pancreas but not in intestine and suggested involvement of Arx in differential regulation of proliferation of Gcg-expressing cells. These results illustrated that Gcg-derived peptides are dispensable for survival and maintaining normoglycemia in adult mice and that Gcg-derived peptides differentially regulate proliferation/differentiation of alpha-cells and L-cells. The present model is useful for analyzing glucose/energy metabolism in the absence of Gcg-derived peptides. It is useful also for analysis of the development, differentiation, and function of Gcg-expressing cells, because such cells are readily visualized by fluorescence in this model.

Beneficial Effects of Cocoa in Perivascular Mato Cells of Cerebral Arterioles in SHR-SP (Izm) Rats.

As previously reported, the cerebral arterioles are surrounded by unique perivascular Mato cells. They contain many inclusion bodies rich in hydrolytic enzymes, and have strong uptake capacity. They are thus considered scavenger cells of vascular and neural tissues in steady-state. In this study, employing hypertensive SHR-SP (Izm) rats, the viability of Mato cells was investigated. In hypertensive rats, the capacity for uptake of horse radish peroxidase (HRP) and the activity of acid phosphatase (ACPase) of Mato cells were markedly reduced, and on electron-microscopic examination Mato cells were found to include heterogeneous contents and appeared electron-dense and degenerated. Vascular cells exhibited some signs of pathology. However, in hypertensive rats fed chow containing 0.25% cocoa, the uptake capacity and ACPase activity of Mato cells for HRP were enhanced, and on electron-microscopic examination Mato cells appeared healthy, with mitochondria with nearly normal profiles. Signs of pathology in vascular cells were also decreased. Superoxides may impair Mato cells and vascular cells.

Enhanced gene expression of myocardial matrix metalloproteinases 2 and 9 after acute treatment with doxorubicin in mice.

We investigated the expression of the genes for matrix metalloproteinases (MMP)-2 and MMP-9 in the ventricle for 1, 2 and 4 days after acute treatment with doxorubicin (DOX) to induce cardiomyopathy in mice, at a single dose of 25 mg kg(-1). Ventricle weights, ventricle weight-to-tail length ratios, and left ventricular systolic and diastolic internal dimensions all decreased time-dependently. Histology showed increased vacuolisation of cardiomyocytes in the DOX-treated mice on day 4 compared with controls. Northern blot hybridisation revealed that MMP-2 and MMP-9 gene transcripts increased in the ventricle of DOX-treated mice on day 2. MMP-2 mRNA approximately doubled in the DOX-treated mice on days 1 and 2, measured using quantitative real-time reverse transcription polymerase chain reaction. By contrast, MMP-9 mRNA expression did not differ in either group on day 1, whereas it increased significantly to 2.9-fold and 2.1-fold in the DOX-treated mice on days 2 and 4, respectively. Consequently, MMP-2 and MMP-9 gene expressions are induced in the ventricle after treatment with DOX, indicating that they might play an important role in the development of DOX-induced cardiotoxicity.

Induction of heparanase gene expression in ventricular myocardium of rats with isoproterenol-induced cardiac hypertrophy.

Gene expression of heparanase, matrix metalloproteinases (MMP)-2 and MMP-9 were examined in ventricles after chronic treatment with isoproterenol (ISO) induced cardiac hypertrophy in rats. Rats were treated with ISO (4 mg/kg, intraperitoneal) twice daily for 4 d. Ventricle weight of the heart and the ventricle weight/body weight ratio were increased respectively by 22% and 25% compared with control rats. Histology showed considerable cardiomyocyte hypertrophy in the ISO-treated rats in comparison to control rats. Northern blot hybridization revealed that heparanase and MMP-2 gene transcripts increased significantly in the ventricles of ISO-treated rats, whereas MMP-9 gene expression was not induced. Thus, heparanase and MMP-2 gene expressions are induced in the ventricle after chronic treatment with ISO, indicating that they might play an important role in development of ISO-induced cardiac hypertrophy.

Ingested cocoa can prevent high-fat diet-induced obesity by regulating the expression of genes for fatty acid metabolism.

OBJECTIVE: We previously found that ingested cocoa decreased visceral adipose tissue weight in rat. To elucidate the molecular mechanisms of that effect, we carried out experiments aimed at analyzing biochemical parameters and gene expression profiles. METHODS: Rats were fed either of two high-fat diets, differing only in supplementation with real or mimetic cocoa. On day 21, body weights, mesenteric white adipose tissue weights, and concentrations of serum triacylglycerol were measured. To investigate the molecular mechanisms underlying the effects of cocoa on lipid metabolism and triacylglycerol accumulation, we examined gene expression profiles in liver and mesenteric white adipose tissues using the GeneChip microarray system. RESULTS: Final body weights and mesenteric white adipose tissue weights were significantly lower in rats fed the real cocoa diet than in those fed the mimetic cocoa diet (P<0.05), and serum triacylglycerol concentrations tended to be lower in rats fed the real cocoa diet (P=0.072). DNA microarray analysis showed that cocoa ingestion suppressed the expression of genes for enzymes involved in fatty acid synthesis in liver and white adipose tissues. In white adipose tissue, cocoa ingestion also decreased the expression of genes for fatty acid transport-relating molecules, whereas it upregulated the expression of genes for uncoupling protein-2 as a thermogenesis factor. CONCLUSIONS: Ingested cocoa can prevent high-fat diet-induced obesity by modulating lipid metabolism, especially by decreasing fatty acid synthesis and transport systems, and enhancement of part of the thermogenesis mechanism in liver and white adipose tissue.