Adrenal cortex development and related disorders leading to adrenal insufficiency.

The adult human adrenal cortex produces steroid hormones that are crucial for life, supporting immune response, glucose homeostasis, salt balance and sexual maturation. It consists of three histologically distinct and functionally specialized zones. The fetal adrenal forms from mesodermal material and produces predominantly adrenal C19 steroids from its fetal zone, which involutes after birth. Transition to the adult cortex occurs immediately after birth for the formation of the zona glomerulosa and fasciculata for aldosterone and cortisol production and continues through infancy until the zona reticularis for adrenal androgen production is formed with adrenarche. The development of this indispensable organ is complex and not fully understood. This article gives an overview of recent knowledge gained of adrenal biology from two perspectives: one, from basic science studying adrenal development, zonation and homeostasis; and two, from adrenal disorders identified in persons manifesting with various isolated or syndromic forms of primary adrenal insufficiency

Development and function of the fetal adrenal.

The adrenal cortex undergoes multiple structural and functional rearrangements to satisfy the systemic needs for steroids during fetal life, postnatal development, and adulthood. A fully functional adrenal cortex relies on the proper subdivision in regions or 'zones' with distinct but interconnected functions, which evolve from the early embryonic stages to adulthood, and rely on a fine-tuned gene network. In particular, the steroidogenic activity of the fetal adrenal is instrumental in maintaining normal fetal development and growth. Here, we review and discuss the most recent advances in our understanding of embryonic and fetal adrenal development, including the known causes for adrenal dys-/agenesis, and the steroidogenic pathways that link the fetal adrenal with the hormone system of the mother through the fetal-placental unit. Finally, we discuss what we think are the major open questions in the field, including, among others, the impact of osteocalcin, thyroid hormone, and other hormone systems on adrenal development and function, and the reliability of rodents as models of adrenal pathophysiology

Antibiotic drug not always the culprit: Allergy to a homoeopathic product.

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Thu0349 autologous fat grafting in the treatment of patients with systemic sclerosis: current experience and future prospects

none13nomixedSpinella, Amelia; Pignatti, Marco; Citriniti, Giorgia; Lumetti, Federica; Cocchiara, Emanuele; Palermo, Adalgisa; Sighinolfi, Gianluca; Pacchioni, Lucrezia; Zaccaria, Giovanna; Lusetti, Irene Laura; Santis, Giorgio De; Salvarani, Carlo; Giuggioli, DiliaSpinella, Amelia; Pignatti, Marco; Citriniti, Giorgia; Lumetti, Federica; Cocchiara, Emanuele; Palermo, Adalgisa; Sighinolfi, Gianluca; Pacchioni, Lucrezia; Zaccaria, Giovanna; Lusetti, Irene Laura; Santis, Giorgio De; Salvarani, Carlo; Giuggioli, Dili

β[beta]-Catenin and FGFR2 regulate postnatal rosette-based adrenocortical morphogenesis

Rosettes are widely used in epithelial morphogenesis during embryonic development and organogenesis. However, their role in postnatal development and adult tissue maintenance remains largely unknown. Here, we show zona glomerulosa cells in the adult adrenal cortex organize into rosettes through adherens junction-mediated constriction, and that rosette formation underlies the maturation of adrenal glomerular structure postnatally. Using genetic mouse models, we show loss of beta-catenin results in disrupted adherens junctions, reduced rosette number, and dysmorphic glomeruli, whereas beta-catenin stabilization leads to increased adherens junction abundance, more rosettes, and glomerular expansion. Furthermore, we uncover numerous known regulators of epithelial morphogenesis enriched in beta-catenin-stabilized adrenals. Among these genes, we show Fgfr2 is required for adrenal rosette formation by regulating adherens junction abundance and aggregation. Together, our data provide an example of rosette-mediated postnatal tissue morphogenesis and a framework for studying the role of rosettes in adult zona glomerulosa tissue maintenance and function

Heavy metals accumulation in willows growing on Spolic Technosols from the abandoned Imperina Valley mine in Italy

Human activities such as metals mining and milling operations provide one of the most important sources of contamination in the environment. Abandoned mines can be an important source of toxic elements. The threat of heavy metal pollution posed by mine soils generally concerns more than one metal. The aim of this study was to assess total concentration of six potentially toxic metals (Cd, Cr, Cu, Pb, Zn and Fe) in the soil and plant samples of three dominant willow species (Salix purpurea L., Salix caprea L. and Salix eleagnos Scop.) collected from abandoned mixed sulphide mine dumps (Imperina Valley, North-east Italy).Results demonstrate that metal concentrations in soils are in general above the Italian average limits and they are also significantly (except Cr), as compared with controls (p≤0.05), with averages of 2.12mgCdkg-1, 2267mgCukg-1, 9552mgPbkg-1, 1243mgZnkg-1 and 299,973mgFekg-1. The phytoremediation ability of selected Salix species for heavy metals was estimated. The results have revealed significant differences among willow species (p. ≤. 0.05) regardless of the species selected. The transfer factor and bioaccumulation coefficient of selected metals varied among plant species and from different sites. Some of the investigated species have potential for soil stabilization and extraction of heavy metals. The results indicate that there is an increasing need for further research projects mainly focused on the mechanisms whereby such willows are able to survive in contaminated soil

Heavy metals accumulation in willows growing on Spolic Technosols from the abandoned Imperina Valley mine in Italy

Human activities such as metals mining and milling operations provide one of the most important sources of contamination in the environment. Abandoned mines can be an important source of toxic elements. The threat of heavy metal pollution posed by mine soils generally concerns more than one metal. The aim of this study was to assess total concentration of six potentially toxic metals (Cd, Cr, Cu, Pb, Zn and Fe) in the soil and plant samples of three dominant willow species (Salix purpurea L., Salix caprea L. and Salix eleagnos Scop.) collected from abandoned mixed sulphide mine dumps (Imperina Valley, North-east Italy).Results demonstrate that metal concentrations in soils are in general above the Italian average limits and they are also significantly (except Cr), as compared with controls (p≤0.05), with averages of 2.12mgCdkg-1, 2267mgCukg-1, 9552mgPbkg-1, 1243mgZnkg-1 and 299,973mgFekg-1. The phytoremediation ability of selected Salix species for heavy metals was estimated. The results have revealed significant differences among willow species (p. ≤. 0.05) regardless of the species selected. The transfer factor and bioaccumulation coefficient of selected metals varied among plant species and from different sites. Some of the investigated species have potential for soil stabilization and extraction of heavy metals. The results indicate that there is an increasing need for further research projects mainly focused on the mechanisms whereby such willows are able to survive in contaminated soil

Targeting canonical BMP signaling : SMAD4 in limb patterning and differentiation

The developing limb is an ideal genetic model to investigate basic developmental mechanisms and signaling networks. The Bone Morphogenetic Protein (BMP) signaling pathway has been associated with a number of context-specific functions during limb development, including establishment of the limb signalling domains, regulation of cell proliferation and cell death, digit patterning, differentiation of the endochondral skeleton and the soft tissue. The present work aimed at providing insights into the roles of canonical BMP signaling in mouse limb bud patterning and tissue differentiation. The canonical BMP pathway includes numerous components, which are often functionally redundant. Conversely, the non-redundant intracellular transducer SMAD4 is essential for gastrulation, such that its inactivation results in an early lethal phenotype and prevents the analysis of its functions during limb development. For the purpose of our investigation, we used the conditional inactivation of the Smad4 gene to generate time- and space-restricted loss-of-function models during limb development. This approach allowed us to show that mesenchymal SMAD4 is dispensable for establishment of the Apical Ectodermal Ridge (AER), which is an ectodermal source of the Fibroblast Growth Factor (FGF) signalling factors that contribute to proximo-distal (P-D) limb axis extension. However, mesenchymal SMAD4 contributes to the establishment the SHH/GREM1/AER-FGFs feedback loop that controls limb outgrowth and patterning. Most importantly, we observed a discrete temporal requirement of SMAD4 for the specification of digit primordia during a developmental period when high BMP activity is essential to initiate chondrogenesis. Specific inactivation of SMAD4 in the limb mesenchyme at this stage is sufficient to inhibit the initiation of mesenchymal condensations, which represent the first structures committed to endochondral bone formation. In fact, the Smad4 deficiency results in the absence of any limb skeletal elements. Molecular evidence indicates that the discrete pattern of genes that normally specify the chondrogenic fate is replaced by wide-spread up-regulation of genes relevant to tendon and joint development in Smad4 deficient limb bud, but no ectopic tendons or joints are formed. These observations suggest a role for SMAD4 in cell fate restriction and differentiation of lateral plate mesoderm-derived tissues in the limb. To further analyze the rapid changes in BMP activity during limb development, we sought to generate a mouse model which senses BMP activity in a specific and dynamic fashion. For the purpose of this project, I have established the aggregation chimera technique to allow for the rapid investigation of cis-regulatory elements in the context of the Gt(ROSA)26Sor locus

To BMP or not to BMP during vertebrate limb bud development

The analysis of vertebrate limb bud development provides insight of general relevance into the signaling networks that underlie the controlled proliferative expansion of large populations of mesenchymal progenitors, cell fate determination and initiation of differentiation. In particular, extensive genetic analysis of mouse and experimental manipulation of chicken limb bud development has revealed the self-regulatory feedback signaling systems that interlink the main morphoregulatory signaling pathways including BMPs and their antagonists. It this review, we showcase the key role of BMPs and their antagonists during limb bud development. This review provides an understanding of the key morphoregulatory interactions that underlie the highly dynamic changes in BMP activity and signal transduction as limb bud development progresses from initiation and setting-up the signaling centers to determination and formation of the chondrogenic primordia for the limb skeletal elements