Molecular and cellular pediatrics最新文献

Background: Subcutaneous fat necrosis of the newborn (SCFN) is a rare disease occurring in the first days of life. Characteristically, the infants show hard nodules in subcutaneous tissue, purple or erythematous in color and appear on the upper back, cheeks, buttocks and limbs. In most cases, SCFN is a self-limiting disease, as the nodules disappear in up to 6 months. A severe complication associated with SCFN is hypercalcaemia. Pathophysiological mechanisms causing SCFN or associated hypercalcaemia are not fully understood yet.

Methods: A systematic literature research including the six biggest databases for medical research has been used to identify all published case reports of SCFN. N = 206 publications has been identified containing n = 320 case reports. All cases have been classified into four subgroups (depending on reported serum-calcium-level): hypercalcaemia, normocalcaemia, hypocalcaemia or no information given. Reported maternal factors, birth characteristics, details about SCFN, diagnostics, therapy and long-term observations have been extracted from publications.

Results: This is the first systematic literature research that summed up all published cases of SCFN from 1948 up to 2018. Information about serum calcium level was given in 64.3% of the cases. From those, the majority showed hypercalcaemia (70.5%) (normocalcaemia 25.1%, hypocalcemia 4.3%). 89.3% of newborns with hypercalcaemia showed suppressed levels of the parathormone. Maternal gestational diabetes, maternal hypertensive diseases during pregnancy, macrosomia (> 4000g), asphyxia and therapeutic hypothermia are risk factors for SCFN. Histological findings showed a granulomatous inflammation in 98% of cases.

Conclusion: We identified that maternal, birth characteristics and therapeutic measures are probably risk factors for SCFN. These risk factors should be taken into account within the care of neonates.

Background: A series of noxae can evoke the termination of nephron formation in preterm and low birth weight babies. This results in oligonephropathy with severe consequences for health in the later life. Although the clinical parameters have been extensively investigated, little is known about the initial damage. Previous pathological findings indicate the reduction in width of the nephrogenic zone and the lack of S-shaped bodies. Current morphological investigations suggest that due to the mutual patterning beside the forming nephron, also its structural neighbors, particularly the interjacent interstitium, must be affected. However, beside the findings on integrative and mastering functions, systematic microanatomical data explaining the configuration of the interstitium at the developing nephron in the fetal kidney during advanced pregnancy is not available. Therefore, this work explains the typical features.

Results: The generated data depicts that the progenitor cells, nephrogenic niche, pretubular aggregate, and mesenchymal-to-epithelial transition are restricted to the subcapsular interstitium. During the proceeding development, only the distal pole of the renal vesicles and comma- and S-shaped bodies stays in further contact with it. The respective proximal pole is positioned opposite the peritubular interstitium at the connecting tubule of an underlying but previously formed nephron. The related medial aspect faces the narrow peritubular interstitium of a collecting duct (CD) ampulla first only at its tip, then at its head, conus, and neck, and finally at the differentiating CD tubule. The lateral aspect starts at the subcapsular interstitium, but then it is positioned along the wide perivascular interstitium of the neighboring ascending perforating radiate artery. When the nephron matures, the interstitial configuration changes again.

Conclusions: The present investigation illustrates that the interstitium at the forming nephron in the fetal kidney consists of existing, transient, stage-specific, and differently far matured compartments. According to the developmental needs, it changes its shape by formation, degradation, fusion, and rebuilding.

In the neonatal lung, exposure to both prenatal and early postnatal risk factors converge into the development of injury and ultimately chronic disease, also known as bronchopulmonary dysplasia (BPD). The focus of many studies has been the characteristic inflammatory responses provoked by these exposures. Here, we review the relationship between immaturity and prenatal conditions, as well as postnatal exposure to mechanical ventilation and oxygen toxicity, with the imbalance of pro- and anti-inflammatory regulatory networks. In these conditions, cytokine release, protease activity, and sustained presence of innate immune cells in the lung result in pathologic processes contributing to lung injury. We highlight the recruitment and function of myeloid innate immune cells, in particular, neutrophils and monocyte/macrophages in the BPD lung in human patients and animal models. We also discuss dissimilarities between the infant and adult immune system as a basis for the development of novel therapeutic strategies.

Background: Chronic kidney disease (CKD) is a global burden affecting both children and adults. Novel imaging modalities hold great promise to visualize and quantify structural, functional, and molecular organ damage. The aim of the study was to visualize and quantify murine renal vasculature using label-free raster scanning optoacoustic mesoscopy (RSOM) in explanted organs from mice with renal injury.

Material and methods: For the experiments, freshly bisected kidneys of alpha 8 integrin knock-out (KO) and wildtype mice (WT) were used. A total of n=7 female (n=4 KO, n=3 WT) and n=6 male animals (n=2 KO, n=4 WT) aged 6 weeks were examined with RSOM optoacoustic imaging systems (RSOM Explorer P50 at SWL 532nm and/or ms-P50 imaging system at 532 nm, 555 nm, 579 nm, and 606 nm). Images were reconstructed using a dedicated software, analyzed for size and vascular area and compared to standard histologic sections.

Results: RSOM enabled mapping of murine kidney size and vascular area, revealing differences between kidney sizes of male (m) and female (f) mice (merged frequencies (MF) f vs. m: 52.42±6.24 mm² vs. 69.18±15.96 mm², p=0.0156) and absolute vascular area (MF f vs. m: 35.67±4.22 mm² vs. 49.07±13.48 mm², p=0.0036). Without respect to sex, the absolute kidney area was found to be smaller in knock-out (KO) than in wildtype (WT) mice (WT vs. KO: MF: p=0.0255) and showed a similar trend for the relative vessel area (WT vs. KO: MF p=0.0031). Also the absolute vessel areas of KO compared to WT were found significantly different (MF p=0.0089). A significant decrease in absolute vessel area was found in KO compared to WT male mice (MF WT vs. KO: 54.37±9.35 mm² vs. 34.93±13.82 mm², p=0.0232). In addition, multispectral RSOM allowed visualization of oxygenated and deoxygenated parenchymal regions by spectral unmixing.

Conclusion: This study demonstrates the capability of RSOM for label-free visualization of differences in vascular morphology in ex vivo murine renal tissue at high resolution. Due to its scalability optoacoustic imaging provides an emerging modality with potential for further preclinical and clinical imaging applications.

Different gastrointestinal pathogens cause diarrhea which is a very common problem in children aged under 5 years. Among bacterial pathogens, Shigella is one of the main causes of diarrhea among children, and it accounts for approximately 11% of all deaths among children aged under 5 years. The case-fatality rates for Shigella among the infants and children aged 1 to 4 years are 13.9% and 9.4%, respectively. Shigella uses unique effector proteins to modulate intracellular pathways. Shigella cannot invade epithelial cells on the apical site; therefore, it needs to pass epithelium through other cells rather than the epithelial cell. After passing epithelium, macrophage swallows Shigella, and the latter should prepare itself to exhibit at least two types of responses: (I) escaping phagocyte and (II) mediating invasion of and injury to the recurrent PMN. The presence of PMN and invitation to a greater degree resulted in gut membrane injuries and greater bacterial penetration. Infiltration of Shigella to the basolateral space mediates (A) cell attachment, (B) cell entry, (C) evasion of autophagy recognition, (D) vacuole formation and and vacuole rapture, (E) intracellular life, (F) Shiga toxin, and (G) immune response. In this review, an attempt is made to explain the role of each factor in Shigella infection.