This short note illustrates facial and head features found in a stone sculpture of the ancient, Precolumbian period in a temple of the Mayan city of Copan (Honduras). The authors believe that this observation may support paleoanthropological evidence of Paget's disease of bone, an osteodystrophy described in the Mesoamerican Indian populations before the first millennium A.D.

[...] It is now required to list each part needed for mucous excretion. They are two ducts in the brain substance, then a thin portion of membrane shaped as the infundibulum, then the gland that receives the tip of this infundibulum and the ducts that drive the mucus (pituita) from this gland to the palate and nares. [...] and I said that one (duct) [...] from the middle of the common cavity (third ventricle) descends [...] into the brain substance, and the end of this duct is [...] the sinus of the gland where the brain mucus is collected [...].

It is currently known that a number of human vascular systems have a fractal geometry. Since we have recently developed a technique to prototype single arterial branches of human soft tissue organs by additive layer manufacturing (AM), we have explored the possibility that auto-similarity in vessel branching represents a key variable for accurate computational modeling of the organ three-dimensional (3D) macro/microscopic anatomy, and its reproduction by inverse engineering. To this purpose, ramification features of the intralobar arteries of the human thyroidwere studied using injection-corrosion casts of the cadaveric gland. Vessel diameters, ramification angles, and branch lengths were measured by light microscopic, computer-aided optical metrology. Distribution of morphological variables was considered on a cumulative basis, and special focus was given to the branching laws. To reduce the bias of vascular distortion due to the pressure of intravascular resin injection, measures were made dimensionless through the use of a scaling parameter set on the vascular caliber of major afferent arteries. In addition, using high resolution microtomography (mCT Skyscan 1172, Bruker microCT) equipped with CTAn software and the Otsu algorithm for segmentation, spaces occupied by vascular branches (referred to as Volume of Interests, VOI) were selected, and their planar fractal dimension calculated. Finally, a computational simulation of the vascular tree was achieved using a mixed, stochastic/deterministic algorithm, based on diffusion limited aggregation (DLA), constrained by mean values of vascular variables. Ratios among decreasing cast calibers, ramification angles, and branch lengths, respectively, were found strictly interrelated, mCT-VOI depicted fractal dimensions, and DLA simulation led to a fractal-like organization consistent with real data morphometrics. In summary, thyroid arterial geometry reliably exhibited a degree of auto-similarity, suggesting that fractality is a key feature for computational modeling and eventual AM of 3D vascular networks of the human thyroid.

In mammals and man, historical investigation suggests that early recognition for a role of the hypothalamus as a site for integration of endocrine, autonomic and behavioral responses can be dated to the 2nd -18th centuries A.D. Although the hypothalamus comprises only 2% of the total brain volume, it is a key regulator of pituitary function and homeostatic balance. In this chapter, we provide an overview of the historical landmarks, embryologic, gross, microscopic and functional anatomy of the mammalian and human hypothalamus and pituitary, and how the hypothalamus relates to the rest of the brain and responds to peripheral signals. In particular, we show that its rostral, nuclear portion exerts prominent regulation of homeostatic behaviors related to energy balance and reproduction. The two caudal portions are primarily involved in ensuring adequate metabolic resources for defensive and exploratory behaviors and responses to sudden changes in endogenous and exogenous stimuli. In addition, we discuss how its network of neurons is made of cells with different functions (neurosecretory, autonomic, motor), how they interact, and how these neural circuitries are woven into a complex architecture of conduits for the movement of intercellular fluids (vasculature, glymphatic channels, meningeal lymphatic vessels). Finally, we focus on the hypothalamic mechanisms involved in the regulation of anterior and posterior pituitary secretion (hypothalamic tuberoinfundibular and neurohypophysial systems), as well those involved in food and fluid intake, lactation, thermoregulation, circadian rhythmicity and the sleep-wake cycle. For complete coverage of all related areas of Endocrinology, please see our online FREE web-book, www.endotext.org .

Scientific research on tissue regeneration is increasingly becoming the most promising response to a number of disabling pathologies with huge impact on the progressively growing and ageing world population. The biomimicry of scaffolds with the target tissue is now universally considered to be a key requirement to properly instruct cells towards the restoration of physiological functioning. In this respect, the present chapter presents an overview of recent findings on biomimetic materials and devices addressed to bone and osteochondral tissues as well as soft organ regeneration. Particular focus is given to new apatite phases, including the newly discovered superparamagnetic apatite and processes to develop ceramic, polymeric and hybrid regenerative scaffolds.

We describe an innovative methodology combining Additive Layer Manufacturing (ALM) and indirect replication to reconstruct reticular-like, three-dimensional (3D) structures mimicking the vascular network of soft tissue and endocrine organs. Using a fractal-like algorithm capable of modelling the intraparenchymal vascular distribution of these viscera, single intraglandular branches of the human thyroid arteries were prototyped with synthetic resin, based on the algorithmic standard to layer (STL) output and ALM techniques. Satisfactory dimensional accuracy was obtained for these models, which were used as masters to evaluate protocols for their indirect replication, through both single and double procedures. Additional studies were conducted using casts of the human kidney arteries, obtained by injection/corrosion of the isolated organ. Satisfactory 3D reproduction of the external morphology of the kidney vessels was achieved. We conclude that our approach has the potential to develop up to the reconstruction with biomaterials of an entire, intraparenchymal vascular tree of soft tissue and endocrine organs.

We describe an innovative methodology combining Additive Layer Manufacturing (ALM) and indirect replication to reconstruct reticular-like, three-dimensional (3D) structures mimicking the vascular network of soft tissue and endocrine organs. Using a fractal-like algorithm capable of modelling the intraparenchymal vascular distribution of these viscera, single intraglandular branches of the human thyroid arteries were prototyped with synthetic resin, based on the algorithmic standard to layer (STL) output and ALM techniques. Satisfactory dimensional accuracy was obtained for these models, which were used as masters to evaluate protocols for their indirect replication, through both single and double procedures. Additional studies were conducted using casts of the human kidney arteries, obtained by injection / corrosion of the isolated organ. Satisfactory 3D reproduction of the external morphology of the kidney vessels was achieved. We conclude that our approach has the potential to develop up to the reconstruction with biomaterials of an entire, intraparenchymal vascular tree of soft tissue and endocrine organs.

In this paper preliminary results are summarized on the use of a combined Additive Layer Manufacturing (ALM) and indirect replication methodology to reconstruct reticular-like, three-dimensional (3D) structures mimicking the 3D vascular network of the adult human thyroid gland. In a first step, we developed a fractal-like algorithm capable of modeling the native arterial distribution of the adult thyroid lobe, allowing for vascular growth within its geometrical domain. Although some arbitrary simplifications were adopted, yet the vascular density of the computational simulation showed good consistency with that of a native thyroid lobe. In a second step, single vascular branches were prototyped based on the STL output of the algorithm and ALM techniques, up to the achievement of a model having satisfactory geometrical/morphological accuracy. In a third step, the problem of reproducing the vascular geometry with a biocompatible polymer was addressed, and different protocols of replication technology were evaluated. Limits and possible methodological solutions are discussed.

The Tenchini Project was born in 2008 at the MAFS (Departmental Museum of Human Anatomy, Pharmacology and Medical-Forensic Sciences) of Parma University. It combines the technical skills of the ENEA Protocenter Laboratory and the CINECA Visit Laboratory of Bologna and has national and international scope, availing itself of expert scientific collaboration. Its short-term aim is to construct a virtual multi-media hyper-test, navigable in internet, concerning the anatomical material of the Tenchini Collection, conserved at the MAFS of Parma. A first version of this hyper-test is already visible on the website www.anfamedmuseo.unipr.it. It also has the long-term aim of contributing to the development of biomedical robotics, and in particular to the generation and training of automata equipped with evolutional capacity. Overall, the project is placed at the service of a specific healthcare requirement, that of improving the technical reliability of surgical and diagnostic procedures operated by machines, especially in extreme situations where the action of human operators is severely limited.

This chapter reveals that the maintenance of normal thyroid function is recognized to be dependent on a complex interplay between the hypothalamus, anterior pituitary, and thyroid gland, as well as other factors that influence the function of these organ systems. The major hormone responsible for the secretion of thyroid hormone from the thyroid is thyroid-stimulating hormone (TSH), also termed thyrotropin. TSH is secreted from anterior pituitary thyrotropes, which comprise approximately 10% of the anterior pituitary cells, and in turn, is positively regulated by thyrotropin-releasing hormone (TRH), originating in the hypothalamus. The free fraction of thyroid hormone circulating in the bloodstream feeds back, both on the anterior pituitary and hypothalamus, to inhibit the secretion of TSH and TRH, respectively, thereby completing what is recognized as a classic example of a negative feedback loop system.

The morphogenetic events leading to the transendothelial passage of lymphoid and tumoral cells are analyzed in light of a very recent and global theory of intercellular communication designated as the Triune Information Network (TIN). The TIN system is based on the assumption that cell-cell interactions primarily occur through cell surface informations or topobiological procesess, whose mechanisms rely upon expression of adhesion molecules, and are regulated by an array of locally-borne (autocrine/paracrine signals and autonomic inputs) and distantly-borne (endocrine secretions) messages. The final aim of the TIN is to control homeostatic functions crucial for the organism survival, like morphogenesis. Knowledge of the TIN signals involved in lymphoid and tumoral cell intravasation might offer a new perspetive to study the mechanisms of tumor immunity. Recognition of tumor target cells by immune cytotoxic effectors, in fact, can be considered a notable case of TIN-mediated cell to cell interaction. In particular, Natural Killer (NK) cells play a role in the cell-mediated control of tumor growth and metastatic spreading. Cell targeting and killing are dependent on the different NK cell receptors and on the efficacy of NK cells after cytokine and monoclonal antibody administration in cancer therapy. Since efficacy of NK cell-based immunotheraphy has been proven in KIR-mismatch regimens or in TRAIL-dependent apoptosis, the ability to manipulate the balance of activating and inhibitory receptors on NK cells and of their cognate ligands as well as the sensitivity of tumor cells to apoptosis, opens new perspectives for NK cell based immunotherapy.

Effects of primary hypothyroidism (HYPO) on the male gonadal axis are controversial, with only scanty data on the gonadotroph cell response and no information on GnRH tuberoinfundibular neurons, even in animal models. HYPO has been reported to variably induce hypogonadotropic hypogonadism, a hypergonadotropic state, or to have no effects on basal levels of pituitary gonadotropins, both in adult male rats and humans. Similarly, the exogenous administration of GnRH to HYPO rats and humans may increase or decrease gonadotropin secretion. Since inhibitory effects of HYPO on the GnRH-gonadotropin axis are reversed by replacement with L-T4, it has been suggested that thyroid hormone (TH) may regulate tuberoinfundibular GnRH and pituitary gonadotropin biosynthesis and/or secretion. To shed light on this hypothesis, we conducted immunocytochemical studies on the distribution and immunostaining characteristics of hypophysiotropic GnRH neurons, LH, PRL and vasoactive intestinal polypeptide (VIP) immunoreactive (IR) cells in the pituitary of adult, male rats. We show that HYPO reduces IR-GnRH in a restricted population of tuberoinfundibular perikarya and their proximal axons compared to euthyroid controls, but increases IR-VIP both in pituitary cells in direct association with LH-gonadotrophs and within IR-LH cells, itself. We propose that VIP may serve as a juxtacrine/paracrine/autocrine regulator of LH secretion and that, when GnRH biosynthesis is reduced by HYPO, gonadotropin secretion may be rescued by local activating effects of VIP. Polychlorinated biphenyls (PCB), industry toxicants found in food and water, also have inhibitory effects on the gonadal axis, decreasing fertility and suppressing basal and GnRHinduced LH release in male rats. Since PCB may also exert endocrine disruptor-dependent (EDD) effects on the thyroid axis producing a non-thyroidal illness syndrome (NTIS) (coined EDD-NTIS), we developed a rat model of EDD-NTIS to determine whether central hypothyroidism may contribute to the pathophysiology of PCB-induced hypogonadism. On the basis of preliminary animal data, we speculate that one of the mechanisms for Partial Androgen Deficiency of the Aging Male may involve central hypothyroidism and EDD-NTIS, resulting in inhibition of the GnRH-gonadotroph axis.

Neuroendocrine, endocrine and autocrine/paracrine signals contribute to the regulation of basal thyrotroph growth. Thyrotropin-releasing hormone (TRH), somatostatin, thyroid hormone (TH), estrogens (Es) and epidermal growth factor, all may play a role both in normal and tumoral thyrotroph proliferation, acting via either plasma membrane receptors and non-genomic steps or nuclear receptors and gene transcription. Signaling features common to all these ligands are involvement of G protein-coupled receptors, mitogen-activated protein kinase cascade and nuclear polyphosphoinositide cycle. In addition, each growth information, independently from the eliciting factor, may be routed intracellularly following a branched pathway, that often links different transduction systems at common check-points, as the Shc-Grb2-SOS complex. Finally, some ligands (e.g. TRH, TH, Es) may display opposite effects on thyrotroph growth, depending on environmental conditions and state of cell differentiation. These ambiguities of response can be interpreted using a "fuzzy" logic-based model of intracellular signaling. Accordingly, check-points common to different transduction cascades may be envisaged as targets for antitumoral therapy selective to the neoplastic thyrotroph cell.