A study on the relationship between intraglandular arterial distribution and thyroid lobe shape: implications for biotechnology of a bioartificial thyroid.

We have recently hypothesized that structural and secretory components of the adult human thyroid gland maintain constant reciprocal and geometrical relationships, even if changes occur in the three-dimensional (3D) architecture of any of these elements. This means that thyroid morphology could be studied from the point of view of a 3D topology. As a consequence, we have investigated anatomical aspects that could support this assumption. In the present study, we show that the presence of a constant relationship can be demonstrated between the vascular arrangement of the gland, including the extension of intraglandular arterial fields, arterial anastomoses and arterial calibers, and the shape as well as volume of the thyroid. Specifically, a statistically significant difference has been found between the network amplitudes of the superior and inferior thyroid arteries in relation to either a conic or an ellipsoidal geometry of the thyroid lobe. In addition, a direct relationship has been implicated between the distribution of arterial anastomoses and the behavior of the lobe as a single hemodynamic unit. Finally, a statistically significant correlation has been observed between average arterial caliber of the inferior thyroid artery and thyroid volume. On the basis of these results, we propose a model of architectural assembly between stromal and parenchymal elements of the adult thyroid that might prove useful in designing a bioartificial gland ex situ. Potential clinical applications of this principle in regenerative medicine of other endocrine organs are highlighted.

Computation and brain processes, with special reference to neuroendocrine systems.

The development of neural networks and brain automata has made neuroscientists aware that the performance limits of these brain-like devices lies, at least in part, in their computational power. The computational basis of a. standard cybernetic design, in fact, refers to that of a discrete and finite state machine or Turing Machine (TM). In contrast, it has been suggested that a number of human cerebral activites, from feedback controls up to mental processes, rely on a mixing of both finitary, digital-like and infinitary, continuous-like procedures. Therefore, the central nervous system (CNS) of man would exploit a form of computation going beyond that of a TM. This "non conventional" computation has been called hybrid computation. Some basic structures for hybrid brain computation are believed to be the brain computational maps, in which both Turing-like (digital) computation and continuous (analog) forms of calculus might occur. The cerebral cortex and brain stem appears primary candidate for this processing. However, also neuroendocrine structures like the hypothalamus are believed to exhibit hybrid computional processes, and might give rise to computational maps. Current theories on neural activity, including wiring and volume transmission, neuronal group selection and dynamic evolving models of brain automata, bring fuel to the existence of natural hybrid computation, stressing a cooperation between discrete and continuous forms of communication in the CNS. In addition, the recent advent of neuromorphic chips, like those to restore activity in damaged retina and visual cortex, suggests that assumption of a discrete-continuum polarity in designing biocompatible neural circuitries is crucial for their ensuing performance. In these bionic structures, in fact, a correspondence exists between the original anatomical architecture and synthetic wiring of the chip, resulting in a correspondence between natural and cybernetic neural activity. Thus, chip "form" provides a continuum essential to chip "function". We conclude that it is reasonable to predict the existence of hybrid computational processes in the course of many human, brain integrating activities, urging development of cybernetic approaches based on this modelling for adequate reproduction of a variety of cerebral performances.

The bioartificial thyroid: a biotechnological perspective in endocrine organ engineering for transplantation replacement.

A new concept for ex situ endocrine organ bioengineering is presented, focused on the realization of a human bioartificial thyroid gland. It is based on the theoretical assumption and experimental evidence that symmetries in geometrical coordinates of the thyroid tissue remain invariant with respect to developmental, physiological or pathophysiological transformations occuring in the gland architecture. This topological arrangement is dependent upon physical connections established between cells, cell adhesion molecules and extracellular matrix, leading to the view that the thyroid parenchyma behaves like a deformable "putty", moulded onto an elastic stromal/vascular scaffold (SVS) dictating the final morphology of the gland. In particular, we have raised the idea that the geometry of the SVS per se provides pivotal epigenetic information to address the genetically-programmed, thyrocyte and endothelial/vascular proliferation and differentiation towards a functionally mature gland, making organ form a pre-requirementfor organ function. A number of experimental approaches are explored to obtain a reliable replica of a human thyroid SVS, and an informatic simulation is designed based on fractal growth of the thyroid intraparenchymal arterial tree. Various tissue-compatible and degradable synthetic or biomimetic polymers are discussed to act as a template of the thyroid SVS, onto which to co-seed autologous human thyrocyte (TPC) and endothelial/vascular (EVPC) progenitor cells. Harvest and expansion of both TPC and EVPC in primary culture are considered, with specific attention to the selection of normal thyrocytes growing at a satisfactory rate to colonize the synthetic matrix. In addition, both in vitro and in vivo techniques to authenticate TPC and EVPC lineage differentiation are reviewed, including immunocytochemistry, reverse trascriptase-polymerase chain reaction, flow cytomery and proteomics. Finally, analysis of viability of the thyroid construct following implantation in animal hosts is proposed, with the intent to obtain a bioartificial thyroid gland morphologically and functionally adequate for transplantation. We believe that the biotechnological scenario proposed herein may provide a template to construct other, more complex and clinically-relevant bioartificial endocrine organs ex situ, such as human pancreatic islets and the liver, and perhaps a new approach to brain bioengineering.

A meta-analysis of inferior thyroid artery variations in different human ethnic groups and their clinical implications.

We have recently found ethnic differences in superior thyroid artery (STA) variational anatomy. Therefore, we now focus on the inferior thyroid artery (ITA). In particular, we analyze whether presence, numerical variations and site of origin of ITA are influenced by ethnic group and gender, whether and which neck side has the largest arterial caliber, whether differences occur between the presence of ITA and STA, to which extent a non-selective thyroid angiography is effective in visualizing ITA, also in comparison to STA, and which clinical value this information may have in selected pathologies of the thyroid, parathyroid and larynx. A meta-analysis has been performed, including 33 library- and Medline-selected publications on Caucasoids (European and non-European) and East Asians, and a set of original data on European Caucasoids. A total of 6285 Caucasoid and 847 East Asian items, comprising half bodies and arteries, were analyzed. After testing the homogeneity of the available data sources in relation to the anatomical variables under study we calculated a cumulative value for each selected anatomical parameter and evaluated differences using non-parametric statistics. The effectiveness of non-selective thyroid angiography was determined using sensitivity, specificity, positive and negative predictive values. The ITA was more frequently absent in East Asians than in Caucasoids, and respectively either more or less frequently arising from thyrocervical and subclavian arteries, in East Asians versus Caucasoids. In contrast, the ITA was less frequently present both in Caucasoids and East Asians than the STA. In addition, the ITA was more frequently present on the right than on the left side in both ethnic groups, but no neck side predominated in size of arterial caliber in European Caucasoids. Finally, the ITA was more frequently present in East Asian males than females, and the effectiveness of a non-selective thyroid angiography showed higher numbers for ITA than STA in Caucasoids. Statistically significant variations occur in some ITA parameters between Caucasoids and East Asians, and in its presence with respect to STA, within each ethnic group. These differences, together with a sexual dimorphic presence of ITA in East Asians and high effectiveness of its visualization by non-selective angiography in European Caucasoids, may represent an evidence-based supply of anatomical information for analysis in selected pathologies of the thyroid, parathyroid and larynx.