Congenital Zika syndrome is associated with maternal protein malnutrition.

Zika virus (ZIKV) infection during pregnancy is associated with a spectrum of developmental impairments known as congenital Zika syndrome (CZS). The prevalence of this syndrome varies across ZIKV endemic regions, suggesting that its occurrence could depend on cofactors. Here, we evaluate the relevance of protein malnutrition for the emergence of CZS. Epidemiological data from the ZIKV outbreak in the Americas suggest a relationship between undernutrition and cases of microcephaly. To experimentally examine this relationship, we use immunocompetent pregnant mice, which were subjected to protein malnutrition and infected with a Brazilian ZIKV strain. We found that the combination of protein restriction and ZIKV infection leads to severe alterations of placental structure and embryonic body growth, with offspring displaying a reduction in neurogenesis and postnatal brain size. RNA-seq analysis reveals gene expression deregulation required for brain development in infected low-protein progeny. These results suggest that maternal protein malnutrition increases susceptibility to CZS.

Nandrolone decanoate in induced fracture nonunion with vascular deficit in rat model: morphological aspects.

BACKGROUND: The nonunion fracture is a relatively frequent complication in both human and veterinary medicine. Specifically, atrophic fracture nonunions are difficult to treat, with revision surgery usually providing the best prognosis. Anabolic steroids, such as nandrolone decanoate (ND), have been reported to have beneficial clinical effects on bone mass gain during osteoporosis; however, their utility in promoting regeneration in atrophic nonunions has not been documented. Our objective was to examine morphological changes induced by the ND in experimental fracture nonunion with vascular deficit in the rat model. METHODS: Fourteen adult Wistar rats had an atrophic fracture nonunion induced in the diaphysis of their left femur. Rats were allocated into two groups: control group and nandrolone decanoate group. Rats in the latter group were given nandrolone decanoate (1.5 mg/kg IM, once a week, during 4 weeks after confirmation of fracture nonunion radiographically). Radiographic and anatomopathological examination, micro-tomography and histological analysis were assessed to characterize the morphological changes promoted by the nandrolone decanoate use. RESULTS: Based on radiology, anatomopathological evaluation, computed micro-tomography and conventional microscopy, nandrolone decanoate promoted bone regeneration at the fracture nonunion site by increasing the cellularity at the fracture site. Percentage of collagen was not significantly different between groups, consistent with high-quality regenerated bone. CONCLUSION: The anabolic steroid nandrolone decanoate improved bone mass and regeneration without affecting collagen production and therefore has potential for improving outcomes for atrophic fracture nonunion.

Zika virus impairs the development of blood vessels in a mouse model of congenital infection.

Zika virus (ZIKV) is associated with brain development abnormalities such as primary microcephaly, a severe reduction in brain growth. Here we demonstrated in vivo the impact of congenital ZIKV infection in blood vessel development, a crucial step in organogenesis. ZIKV was injected intravenously in the pregnant type 2 interferon (IFN)-deficient mouse at embryonic day (E) 12.5. The embryos were collected at E15.5 and postnatal day (P)2. Immunohistochemistry for cortical progenitors and neuronal markers at E15.5 showed the reduction of both populations as a result of ZIKV infection. Using confocal 3D imaging, we found that ZIKV infected brain sections displayed a reduction in the vasculature density and vessel branching compared to mocks at E15.5; altogether, cortical vessels presented a comparatively immature pattern in the infected tissue. These impaired vascular patterns were also apparent in the placenta and retina. Moreover, proteomic analysis has shown that angiogenesis proteins are deregulated in the infected brains compared to controls. At P2, the cortical size and brain weight were reduced in comparison to mock-infected animals. In sum, our results indicate that ZIKV impairs angiogenesis in addition to neurogenesis during development. The vasculature defects represent a limitation for general brain growth but also could regulate neurogenesis directly.

X-ray microtomography system for small and light samples using a flat panel detector.

A low-cost system able to perform microtomography of samples such as teeth, insects, or other small materials and low atomic numbers is presented. For this, a small flat panel type sensor was used. The process of characterization of the detector is detailed, as well as its main characteristics. The electromechanical control and the software used are also described. The advantages, some limitations, and comparisons with commercial systems are presented along with some three-dimensional volumetric reconstruction of different materials that served as samples during the development of the system.

Novel rat model of nonunion fracture with vascular deficit.

Nonunion fractures occur frequently in humans, with profound implications (medical and non-medical). Although there are numerous animal models to study pathogenesis and treatment of nonunion fractures, there is apparently the lack of a definitive model for atrophic nonunion fracture. Therefore, the objective was to develop a low-cost rat model of nonunion fracture with a vascular deficit that enabled standardized quantitative analysis of bone growth and regeneration. The model was developed with two surgeries, performed apart. The first involved osteotomy of the femur diaphysis, removal of periosteum and endosteum, isolation of the fracture site using a latex artefact (Penrose drain tube), and reduction of the fracture using an intramedullary pin, whereas the second surgery was to remove the latex artefact. Based on radiographic imaging, micro-CT and histological analyses done 125 days after the fracture was induced, there was clear evidence of atrophic nonunion fracture, without pin migration or specimen loss. Perceived advantages of this model included low cost, ease of reproducibility, lack of specimen loss, and, finally, the potential to assess bone growth and regeneration under poor vascular conditions.