RICKETS AT THE MEDICI COURT OF FLORENCE: THE CASE OF DON FILIPPINO (1577-1582)

Among the children found in the crypt of the Grand Duke Giangastone in S. Lorenzo Basilica (Florence), the skeletal remains of a 5-year-old child still wearing his fine high social status clothing were recovered. This child of the Medici family was identified as Don Filippino (1577-1582), son of the Grand Duke Francesco I (1541-1587) and Giovanna from Austria (1547-1578). The prince showed several pathological deformities of the cranial and post-cranial skeleton, including enlargement of the cranium, thinning of the cranial vault bones (craniotabes), platybasia and marked bending of femora, tibiae and fibulae. Differential diagnosis suggests that Don Filippino was affected by rickets. The occurrence of this metabolic disease related to vitamin D deficiency in a Renaissance high social class individual can be explained by the practice of very prolonged breast-feeding, up until to sunlight. Historical sources describe Don Filippino as frail and sickly, with frequent illnesses and persistent slight fevers, and it can be supposed that the child was frequently confined indoors, especially in the cold season. Integration of osteoarchaeological evidence with historical documentation suggests that bone lesions observed in the skeletal remains of Don Filippino are compatible with a diagnosis of rickets, caused by the custom of prolonged breast-feeding associated with inadequate sunlight exposure two years of age. Maternal milk contains insufficient vitamin D ratios and retarded weaning severely exposes children to a higher risk of developing rickets, especially if dietary habits are combined with inadequate exposure

Expression of calcium-binding proteins and selected neuropeptides in the human, chimpanzee, and crab-eating macaque claustrum

The claustrum is present in all mammalian species examined so far and its morphology, chemoarchitecture, physiology, phylogenesis and ontogenesis are still a matter of debate. Several morphologically distinct types of immunostained cells were described in different mammalian species. To date, a comparative study on the neurochemical organization of the human and non-human primates claustrum has not been fully described yet, partially due to technical reasons linked to the postmortem sampling interval. The present study analyze the localization and morphology of neurons expressing parvalbumin (PV), calretinin (CR), NPY, and somatostatin (SOM) in the claustrum of man (# 5), chimpanzee (# 1) and crab-eating monkey (# 3). Immunoreactivity for the used markers was observed in neuronal cell bodies and processes distributed throughout the anterior-posterior extent of human, chimpanzee and macaque claustrum. Both CR- and PV-immunoreactive (ir) neurons were mostly localized in the central and ventral region of the claustrum of the three species while SOM- and NPY-ir neurons seemed to be equally distributed throughout the ventral-dorsal extent. In the chimpanzee claustrum SOM-ir elements were not observed. No co-localization of PV with CR was found, thus suggesting the existence of two non-overlapping populations of PV and CR-ir interneurons. The expression of most proteins (CR, PV, NPY), was similar in all species. The only exception was the absence of SOM-ir elements in the claustrum of the chimpanzee, likely due to species specific variability. Our data suggest a possible common structural organization shared with the adjacent insular region, a further element that emphasizes a possible common ontogeny of the claustrum and the neocortex

Fibrotic and Vascular Remodelling of Colonic Wall in Patients with Active Ulcerative Colitis

open16noIntestinal fibrosis is a complication of inflammatory bowel disease [IBD]. Although fibrostenosis is a rare event in ulcerative colitis [UC], there is evidence that a fibrotic rearrangement of the colon occurs in the later stages. This is a retrospective study aimed at examining the histopathological features of the colonic wall in both short-lasting [SL] and long-lasting [LL] UC. Surgical samples of left colon from non-stenotic SL [a parts per thousand currency sign 3 years, n = 9] and LL [a parts per thousand yen 10 years, n = 10] UC patients with active disease were compared with control colonic tissues from cancer patients without UC [n = 12] to assess: collagen and elastic fibres by histochemistry; vascular networks [CD31/CD105/nestin] by immunofluorescence; parameters of fibrosis [types I and III collagen, fibronectin, RhoA, alpha-smooth muscle actin [alpha-SMA], desmin, vimentin], and proliferation [proliferating nuclear antigen [PCNA]] by western blot and/or immunolabelling. Colonic tissue from both SL-UC and LL-UC showed tunica muscularis thickening and transmural activated neovessels [displaying both proliferating CD105-positive endothelial cells and activated nestin-positive pericytes], as compared with controls. In LL-UC, the increased collagen deposition was associated with an up-regulation of tissue fibrotic markers [collagen I and III, fibronectin, vimentin, RhoA], an enhancement of proliferation [PCNA] and, along with a loss of elastic fibres, a rearrangement of the tunica muscularis towards a fibrotic phenotype. A significant transmural fibrotic thickening occurs in colonic tissue from LL-UC, together with a cellular fibrotic switch in the tunica muscularis. A full-thickness angiogenesis is also evident in both SL- and LL-UC with active disease, as compared with controls.openIppolito, Chiara; Colucci, Rocchina; Segnani, Cristina; Errede, Mariella; Girolamo, Francesco; Virgintino, Daniela; Dolfi, Amelio; Tirotta, Erika; Buccianti, Piero; Di Candio, Giulio; Campani, Daniela; Castagna, Maura; Bassotti, Gabrio; Villanacci, Vincenzo; Blandizzi, Corrado; Bernardini, NunziaIppolito, Chiara; Colucci, ROCCHINA LUCIA; Segnani, Cristina; Errede, Mariella; Girolamo, Francesco; Virgintino, Daniela; Dolfi, Amelio; Tirotta, Erika; Buccianti, Piero; Di Candio, Giulio; Campani, Daniela; Castagna, Maura; Bassotti, Gabrio; Villanacci, Vincenzo; Blandizzi, Corrado; Bernardini, Nunzi

Immunohistochemical Analysis of Myenteric Ganglia and Interstitial Cells of Cajal in Ulcerative Colitis

Ulcerative colitis (UC) is an inflammatory bowel disease with alterations of colonic motility, which influence clinical symptoms. Although morpho-functional abnormalities in the enteric nervous system have been suggested, in UC patients scarce attention has been paid to possible changes in the cells that control colonic motility, including myenteric neurons, glial cells, and interstitial cells of Cajal (ICC). This study evaluated the neural-glial components of myenteric ganglia and ICC in the colonic neuromuscular compartment of UC patients by quantitative immunohistochemical analysis. Full-thickness archival samples of the left colon were collected from 10 patients with UC (5 M, 5 F; age range, 45-62 years) who underwent elective bowel resection. The colonic neuromuscular compartment was evaluated immunohistochemically in paraffin cross-sections. The distribution and number of neurons, glial cells and ICC were assessed by anti-HuC/D, -S100β and -c-Kit antibodies, respectively. Data were compared with findings on archival samples of normal left colon from 10 sex- and age-matched control patients, who underwent surgery for uncomplicated colon cancer. Compared to controls, patients with UC showed: (a) reduced density of myenteric HuC/D-positive neurons and S100β-positive glial cells, with a loss over 61% and 38%, respectively, and increased glial cell/neuron ratio; (b) ICC decrease in the whole neuromuscular compartment. The quantitative variations of myenteric neuro-glial cells and ICC indicate considerable alterations of the colonic neuromuscular compartment in the setting of mucosal inflammation associated with UC, and provide a morphological basis for better understanding the motor abnormalities often observed in UC patients

Tissue remodelling in the colonic wall of patients with ulcerative colitis

Inflammation-driven tissue remodelling may develop to fibrotic rearrangement. With regard to inflammatory bowel diseases, fibrotic remodelling has been evaluated in Crohn’s disease, while little attention to such processes has been paid to ulcerative colitis (UC) [1]. The present study evaluated the distribution of connective tissue and angiogenesis in colon of patients with UC, paying particular attention to the tonaca muscularis, which is poorly considered in histopathological studies. Full-thickness left colonic samples were obtained from 10 patients with established, severe and pharmacologically unresponsive UC, who underwent bowel resection. Routine histology, histochemistry and immunohistochemistry were conducted in paraffin cross-sections. The distribution of collagen and elastic fibers was evaluated and quantified by both histochemical (Van Gieson, orcein, Verroheff staining) and immunohistochemical (anti-collagen I and III, anti-elastin) assays. The vascular network pattern was studied by anti-CD31 and nestin immunostaining. For comparison, the same evaluations were performed in healthy colonic control samples obtained from 10 subjects, who underwent surgery for uncomplicated colon cancer. A significant increase in collagen fibers and a decrease in elastin content were detected in the UC inflamed colon, as compared with controls. In particular, enhanced collagen deposition (mainly collagen type III) were found at level of submucosa, and tonaca muscularis within the longitudinal muscle (mainly along the serosal side) and circular muscle layer, and in perivascular connective tissue. By contrast, elastic fibers were significantly reduced throughout the whole muscle compartment, with particular regard for the myenteric ridge. Microvessel density was significantly higher in both submucosa and tonaca muscularis of colonic samples from UC patients compared with those from healthy control individuals. The present findings indicate that a significant tissue remodelling occurs in the inflamed colonic wall in patients with UC, also at the level of muscle layers. This rearrangement of the connective fibers and vascular network, together with the known alterations affecting the myenteric neurons and interstitial cells of Cajal, may contribute to the development of enteric dysmotility, and, accordingly, to the serious digestive symptoms which afflict patients with UC

Deranged expression of smooth muscle molecules in colonic tunica muscularis of DD patients

The pathogenesis of diverticular disease (DD) seems to be a result of a complex interaction between exposure to a low-fibre diet, possible genetic influence, coexistence of other bowel disease and impact of medicine use. These conditions may lead to alterations in colonic pressure and motility [1]. To date, histopatological studies in the field of disturbances in intestinal motility have been mainly focused on the enteric nervous system and interstitial cells of Cajal, which have been found to be both variously affected in different conditions of gut dysmotility. By contrast, although smooth muscle cells (SMCs) are well recognized as the final effectors of the enteric neuromuscular units and have been extensively studied by electrophysiological experiments in colonic motility dysfunction, scarce attention has been paid to the molecular abnormalities of enteric musculature in gut dysmotility, and, in particular, data on SMCs in DD are fairly lacking. Accordingly, the aim of the present study was to evaluate the expression patterns of molecules involved in the contractile functions of SMCs within the colonic tunica muscularis from patients with DD. In particular, we examined the expression of the following molecules by immunohistochemistry and image analysis: Cx26 and Cx43, which are prominent components of gap junctions in human colonic SMCs [2], and an array of signaling molecules, which are known to regulate the functions of gap junctions and the contractile activity of SMCs [3,4,5]. The immunohistochemical analysis revealed significant abnormalities in DD samples, concerning both the expression and distribution patterns of most of the investigated molecular factors. Indeed, Cx26, Cx43, PKCps and RhoA appeared to be markedly deranged in all DD colonic samples compared to normal ones, except for α-SMA and pS368-Cx43. The present results provide the first evidence of an altered pattern of factors involved in smooth muscle contractility at level of tunica muscularis SMCs of DD patients. These abnormalities may contribute to the altered motility function, which characterize the colonic tunica muscularis of patients with DD

Preoperative rectal cancer staging with phased-array MR

<p>Abstract</p> <p>Background</p> <p>We retrospectively reviewed magnetic resonance (MR) images of 96 patients with diagnosis of rectal cancer to evaluate tumour stage (T stage), involvement of mesorectal fascia (MRF), and nodal metastasis (N stage).</p> <p>Our gold standard was histopathology.</p> <p>Methods</p> <p>All studies were performed with 1.5-T MR system (Symphony; Siemens Medical System, Erlangen, Germany) by using a phased-array coil. Our population was subdivided into two groups: the first one, formed by patients at T1-T2-T3, N0, M0 stage, whose underwent MR before surgery; the second group included patients at Tx N1 M0 and T3-T4 Nx M0 stage, whose underwent preoperative MR before neoadjuvant chemoradiation therapy and again 4-6 wks after the end of the treatment for the re-staging of disease.</p> <p>Our gold standard was histopathology.</p> <p>Results</p> <p>MR showed 81% overall agreement with histological findings for T and N stage prediction; for T stage, this rate increased up to 95% for pts of group I (48/96), while for group II (48/96) it decreased to 75%.</p> <p>Preoperative MR prediction of histologically involved MRF resulted very accurate (sensitivity 100%; specificity 100%) also after chemoradiation (sensitivity 100%; specificity 67%).</p> <p>Conclusions</p> <p>Phased-array MRI was able to clearly estimate the entire mesorectal fat and surrounding pelvic structures resulting the ideal technique for local preoperative rectal cancer staging.</p

Calcitonin and somatostatin containing C cells in rat and human thyroid. Immunohistochemical study by a double-staining method

C cells of the thyroid probably exert a paracrine control on follicular cells through secretion of peptides such as calcitonin and somatostatin. The aim of the present study was to investigate the expression of different peptides produced by C cells in rat thyroid and in the different morphological and pathological conditions of the human thyroid. Therefore we employed the immunohistochemical double-staining method using anti-calcitonin and anti-somatostatin antibodies. The results of this study show the presence of C cells containing calcitonin and C cells containing somatostatin exclusively in the rat and the human thyroid. This distinction with prevalence of one peptide on the other is maintained in the different morphological and pathological conditions of the human thyroid

Platelet phenolsulphotransferase activity in patients with dementia of Alzheimer type

Human blood platelets are more and more regarded as a reliable model of nerve cells, and some biochemical alterations found in platelet enzyme activities and receptor binding parameters may be related to analogous changes occuring in the central nervous system. Platelet phenol-sulphotransferase activity has been evaluated in some neurological disorders, such as Parkinson's disease and headache. In the present work we determined phenolsulphotransferase activity in platelets of 36 patients with dementia of Alzheimer type, and compared such activity values with those of 36 sex- and age-matched healthy controls. Patients showed a significantly higher platelet phenolsulphotransferase activity than control subjects, both with dopamine and with phenol as substrates. Moreover, a significant positive correlation was found between platelet enzyme activity and severity of illness. These findings are discussed in terms of the biochemical abnormalities found in the central nervous system of demented subjects, and in terms of the possible pathogenetic involvement of an altered phenolsulphotransferase activity (and, in general, of a modified monoamine metabolism) in such derangements of biochemical systems often occuring in dementia of Alzheimer type