Maurizio Sabbatini | Università degli Studi del Piemonte Orientale (original) (raw)

Papers by Maurizio Sabbatini

Research paper thumbnail of J Tissue Eng.pdf

Creative Commons Non Commercial CC-BY-NC: This article is distributed under the terms of the Crea... more Creative Commons Non Commercial CC-BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).

Research paper thumbnail of Journal of Bone and Mineral Metabolism Effect of retinoic acid and vitamin D 3 on osteoblast differentiation and activity in aging

analyzed (the proliferation, differentiation, and new matrix deposition are significantly reduced... more analyzed (the proliferation, differentiation, and new matrix deposition are significantly reduced in aged osteoblasts), with the exception of PPARγ 2 , which we found to be constitutively overexpressed and not modulated by retinoic acid or calcitriol administration. Our findings show the impaired ability of aged osteoblasts to perform adequate functional response and draw attention to the therapeutic approaches for bone healing in elderly patients.

Research paper thumbnail of In vitro mechanical compression induces apoptosis and regulates cytokines release in hypertrophic scars

Wound Repair and Regeneration, 2003

Hypertrophic scars resulting from severe burns are usually treated by continuous elastic compress... more Hypertrophic scars resulting from severe burns are usually treated by continuous elastic compression. Although pressure therapy reaches success rates of 60-85% its mechanisms of action are still poorly understood. In this study, apoptosis induction and release of interleukin-1b (IL-1b) and tumor necrosis factor-a (TNF-a) were evaluated in normal (n ¼ 3) and hypertrophic (¼7) scars from burns after in vitro mechanical compression. In the absence of compression (basal condition) apoptotic cells, scored using terminal deoxyribonucleotidyl transferase assay, were present after 24 hours in the derma of both normal scar (23 ± 0.4% of total cell) and hypertrophic scar (11.3 ± 1.4%). Mechanical compression (constant pressure of 35 mmHg for 24 hours) increased apoptotic cell percentage both in normal scar (29.5 ± 0.4%) and hypertrophic scar (29 ± 1.7%). IL-1b released in the medium was undetectable in normal scar under basal conditions while in hypertrophic scar the IL-1b concentration was 3.48 ± 0.2 ng/g. Compression in hypertrophic scar-induced secretion of IL-1b twofold higher compared to basal condition. (7.72 ± 0.2 ng/g). TNF-a basal concentration measured in normal scar medium was 8.52 ± 4.01 ng/g and compression did not altered TNF-a release (12.86 ± 7.84 ng/g). TNF-a basal release was significantly higher in hypertrophic scar (14.74 ± 1.42 ng/g) compared to normal scar samples and TNF-a secretion was diminished (3.52 ± 0.97 ng/g) after compression. In conclusion, in our in vitro model, mechanical compression resembling the clinical use of elastocompression was able to strongly increase apoptosis in the hypertrophic scar derma as observed during granulation tissue regression in normal wound healing. Moreover, the observed modulation of IL-1b and TNF-a release by mechanical loading could play a key role in hypertrophy regression induced by elastocompression. (WOUND REP REG 2003;11:331-336) Hypertrophic scars (HSs) are the result of alterations in the normal processes of cutaneous wound healing occurring as a consequence of injury of the skin, especially burns. HSs are characterized by excessive deposition of fibroblast-derived extracellular matrix (ECM) proteins, especially collagen, in the derma over long periods of time, 1 by persistent inflammation and by fibrosis. 2 The disregulation of ECM turnover observed in the HS seems to be related to an excessive and persistent synthesis of pro-inflammatory/ fibrogenic cytokines such as interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), platelet derived growth factor and transforming growth factor-b from inflammatory cells. In fact, immunohistochemical analysis of HS cytokine expression has shown that transforming growth factor-b , IL-6 and TNFb are comparable to normal scar (NS), while ECM Extracellular matrix ELISA Enzyme-linked immunosorbent assay HS Hypertrophic scar IL-1b Interleukin-1b NS Normal scar PBS Phosphate buffered saline solution PGE 2 Prostaglandin E 2 TdT Terminal deoxyribonucleotidyl transferase TNF-a Tumor necrosis factor-a From the

Research paper thumbnail of Muscarinic Cholinergic Receptors and Acetylcholinesterase Activity in Umbilical Artery and Vein in Pregnancy-Induced Hypertension (Pre-Eclampsia)

Clinical and Experimental Hypertension, 1997

The influence of pregnancy-induced hypertension (pre-eclampsia) on muscarinic cholinergic recepto... more The influence of pregnancy-induced hypertension (pre-eclampsia) on muscarinic cholinergic receptors and on acetylcholinesterase (AChE) activity was investigated using frozen sections of the umbilical artery and vein. Pre-eclamptic patients undergoing Caesarean delivery and normotensive pregnant control woman undergoing Caesarean delivery with similar parity, gestation length and age were examined. Muscarinic cholinergic receptors were assayed in frozen sections of the umbilical artery and vein by a radioligand binding assay technique, using [3H]-N-methyl scopolamine (NMS) as a ligand. AChE was demonstrated with a histochemical technique associated with microdensitometry. [3H]-NMS was specifically bound to sections of both umbilical artery and vein in a manner consistent with the labelling of muscarinic cholinergic receptors. The affinity of the radioligand was similar in the two vessels, whereas the maximum density of binding sites (Bmax) was higher in the umbilical vein than in the artery. A faint AChE reactivity was observed in the tunica media of both umbilical artery and vein. In pre-eclampsia, a loss of [3H]-NMS binding sites not accompanied by changes in the affinity of radioligand was found. The decrease of muscarinic cholinergic receptors involved to a greater extent the umbilical artery than the vein. No differences in AChE activity were found at the level of umbilical artery and vein between control and pre-eclamptic subjects. These findings suggest that pre-eclampsia is characterized by a loss of muscarinic cholinergic receptors in the umbilical circulation not accompanied by changes of the acetylcholine catabolizing enzyme AChE. It is possible that the decreased density of vascular muscarinic cholinergic receptors in pregnancy-induced hypertension contribute to the increased resistance of the umbilical circulation occurring in pre-eclampsia.

Research paper thumbnail of Activation of caspase-8 triggers anoikis in human neuroblastoma cells

Neuroscience Research, 2006

Cells require appropriate interaction with extracellular matrix proteins mediated by integrins to... more Cells require appropriate interaction with extracellular matrix proteins mediated by integrins to grow, differentiate and survive. Many cell types including nervous cells undergo anoikis, a substrate-dependent apoptosis, when adhesion is impaired. Resistance of tumors to cytotoxic drugs is probably due to disturbed apoptosis programs. The proteolytic enzymes caspases are the main executioners of apoptosis. It was reported that caspase-8 expression is deficient in some neuroblastoma cells. We demonstrated that human neuroblastoma cell line SK-B-BE, differentiated with retinoic acid, expressed caspases 3, 8 and 9. Caspases 8 and 3, but not caspase-9 were activated in SK-N-BE cells cultured in suspension or on aspecific adhesive substrate. Cell positive to caspase-8 were classified into four stages, by morphometric and densitometric parameters. The use of the specific caspase-8 inhibitor Z-IETD-FMK dramatically reduced apoptosis, demonstrating that caspase-8 is the upstream initiator caspase during SK-N-BE cells anoikis. Among matrix proteins, type I collagen is the most effective and fibronectin the least in delaying anoikis. The activation of caspases 8 and 3 by unligated integrins was dependent on the state of neuronal differentiation, since the most differentiated cell was the most vulnerable to anoikis. These data show that activation of caspase-8 is specifically required to promote anoikis in SK-N-BE neuroblastoma cells.

Research paper thumbnail of Effect of the thyrotropin releasing hormone analogue posatirelin (RGH 2202) on microanatomical changes induced by lesions of the nucleus basalis magnocellularis in the rat

Drugs under experimental and clinical research

The effect of 4 and 8 weeks treatment with 10 mg/kg/day of the thyrotropin releasing hormone anal... more The effect of 4 and 8 weeks treatment with 10 mg/kg/day of the thyrotropin releasing hormone analogue posatirelin (L-6-ketopiperidine-2-carbonyl-L-leucyl-proline amide) on microanatomical changes induced by monolateral and bilateral lesions of the nucleus basalis magnocellularis (NBM) were investigated. The following parameters were assessed in the frontal cortex and hippocampus of NBM-lesioned and sham-operated rats: 1) number of nerve cell and glial fibrillary acidic protein (GFAP)-immunoreactive astrocyte profiles; 2) density of silver-gold impregnated fibres; 3) density of choline acetyltransferase (ChAT)-immunoreactive fibres; 4) intensity of acetylcholinesterase (AChE) staining. In NBM-lesioned untreated rats, no changes in the number of nerve cell or of astrocyte profiles were found either in the frontal cortex or in the hippocampus. The only exception was a decrease in the number of granule neuron profiles in the dentate gyrus at 8 weeks after lesioning. Silver-gold impregnated fibres, which express the width of interneuronal connections, were reduced in the hippocampus but not in the frontal cortex of NBM-lesioned rats. ChAT immunoreactivity and AChE reactivity, which were localised respectively in nerve fibre-like structures and in the neuropil, were decreased in the frontal cortex but not in the hippocampus from the fourth week after NBM lesioning. Lesions did not change the number of ChAT-immunoreactive nerve fibres or intensity of AChE staining in the hippocampus. Treatment with posatirelin was without effect on the number of nerve cell profiles or of GFAP-immunoreactive astrocytes both at 4 and 8 weeks after NBM lesioning. Treatment with the compound increased the number of silver-gold impregnated fibres in the hippocampus of NBM-lesioned rats and restored in part ChAT immunoreactivity and AChE reactivity in the frontal cortex. These effects were noticeable in NBM-lesioned rats after 8 weeks of treatment. The possible significance of the neuroprotective effect elicited by posatirelin treatment after lesions of the NBM is discussed.

Research paper thumbnail of Effect of treatment with the neuroactive peptide posatirelin on microanatomical changes of frontal cortex and hippocampus caused by lesions of the locus coeruleus

Drugs under experimental and clinical research

The influence of monolateral and bilateral lesions of the Locus coeruleus (LC) on the number of n... more The influence of monolateral and bilateral lesions of the Locus coeruleus (LC) on the number of nerve cell and glial fibrillary acidic protein (GFAP)-immunoreactive astrocyte profiles, on silver-gold impregnated fibres and on tyrosine hydroxylase (TH) immunoreactivity was assessed in the rat frontal cortex and hippocampus. The influence of treatment for 4 and 8 weeks with a 10 mg/kg/day dose of the neuroactive peptide posatirelin on the above parameters was also investigated. Lesions of the LC decreased the number of nerve cell profiles in the frontal cortex 8 weeks after lesioning and were without effect on nerve cell profiles in the frontal cortex 4 weeks after lesioning and in the hippocampus at both 4 and 8 weeks after LC lesioning. Glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes were not affected by lesions of LC. Silver-gold impregnated fibres were decreased in the frontal cortex but not in the hippocampus of LC-lesioned rats at 8 weeks after lesioning. TH immunoreactivity, which was localized in nerve fibre-like structures both in the frontal cortex and in the hippocampus was decreased in the frontal cortex and in the hippocampus from the 4th week after LC lesioning. Treatment with posatirelin was without effect on the number of nerve cell and of GFAP-immunoreactive astrocyte profiles at both 4 and 8 weeks after LC lesioning, with the exception of nerve cells of the frontal cortex in monolaterally-lesioned rats which were increased 8 weeks after lesioning. The compound increased silver-gold impregnated fibres in the frontal cortex of monolaterally lesioned rats after 8 weeks of treatment, but did not affect TH immunoreactivity both in the frontal cortex or in the hippocampus. The above results suggest that treatment with posatirelin exerts a neuroprotective effect on the frontal cortex consisting of the partial restoration of some microanatomical changes caused by lesions of LC. The possible significance of this effect is discussed.

Research paper thumbnail of Nephroprotective effect of treatment with calcium channel blockers in spontaneously hypertensive rats

Journal of Pharmacology and Experimental Therapeutics

The influence of hypertension and of treatment with some dihydropyridine-type Ca(2+) channel bloc... more The influence of hypertension and of treatment with some dihydropyridine-type Ca(2+) channel blockers and with the nondihydropyridine-type vasodilator hydralazine on the morphology of kidney was investigated in 26-week-old spontaneously hypertensive rats (SHR) and in age-matched Wistar-Kyoto rats. Fourteen-week-old SHR were treated for 12 weeks with a nonhypotensive dose of lercanidipine or with equihypotensive doses of lercanidipine, manidipine, nicardipine, and hydralazine. In control SHR, systolic pressure values were significantly higher in comparison with Wistar-Kyoto rats. Treatment with the low dose of lercanidipine did not reduce systolic blood pressure in SHR, whereas the higher dose of lercanidipine or other compounds tested significantly decreased systolic pressure values. Glomerular hypertrophy accompanied by signs of glomerulosclerosis, increase of mesangial cells, and convoluted tubules degeneration were observed in control SHR. Hypotensive doses of Ca(2+) antagonists countered glomerular injury, the increase of mesangial cells, the reduction of capsular space, and tubular degeneration. Hydralazine, in spite of its hypotensive activity, displayed a slight nephroprotective action. The nonhypotensive dose of lercanidipine countered in part glomerular injury, narrowing of capsular space, and tubular degeneration, and decreased mesangial cell augmentation in SHR. These results suggest that treatment with dihydropyridine-type Ca(+2) antagonists counters hypertensive glomerular and tubular changes occurring in SHR. The demonstration of nephroprotection by the nonhypotensive dose of lercanidipine suggests that the renal effects of the compound may be in part unrelated to its hemodynamic activity.

Research paper thumbnail of Seminar on Hypertension and Brain Damage - Preface

Clinical and Experimental Hypertension

Research paper thumbnail of T-cell subpopulations express a different pattern of dopaminergic markers in intra- and extra-thymic compartments

Journal of biological regulators and homeostatic agents

An involvement of dopamine in regulation of the immune function has been assessed and dopaminergi... more An involvement of dopamine in regulation of the immune function has been assessed and dopaminergic system has been found widely represented in thymus. Nevertheless detail on the characterization of dopaminergic system in assisting thymocytes development and lymphocytes mature physiology are still lacking. The present study was designed to characterize dopamine plasma membrane transporter (DAT), vesicular dopamine transporters (VMAT)-1 and -2, and dopamine D1-like and D2-like receptors in rat thymocytes, splenocytes and peripheral blood mononuclear cells. Western blot and RT-PCR analyses, performed on these cells, showed an expression of dopamine transporters and receptors during thymocyte development (when of CD4 and CD8 markers are differently expressed). Furthermore FACS analysis, indicates that DAT and dopamine D1-like receptors are expressed at high levels in thymocytes, splenocytes, and peripheral lymphocytes. The percentage of CD4+ CD8+ (double-positive) thymocytes expressing ...

Research paper thumbnail of Pharmaco-epidemiological description of the population of the Marche Region (central Italy) treated with the antipsychotic drug olanzapine

Annali dell'Istituto superiore di sanità, 2013

In Italy, even though olanzapine has been discouraged for treatment of behaviour disorders in old... more In Italy, even though olanzapine has been discouraged for treatment of behaviour disorders in older patients affected by dementia, some physicians chose to prescribe for them. In response to this situation, the Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA) promulgated a cautionary note. This study examined epidemiological indices for olanzapine prescriptions between 2004 and 2007 in the Marche Region of central Italy and in its provinces, to assess physician compliance with the AIFA note, and to determine whether there were differences in drug prescription between populations of the same territory, or differences based on gender or age group. Our analyses revealed high olanzapine use among young men and mature women, suggesting that these groups are most prone to psychotic symptoms. Analysis revealed that olanzapine prescription in elderly patients was reduced in some provinces, in line with the AIFA note. Prudent use of olanzapine prescription, in compliance with the AIF...

Research paper thumbnail of Non pigmented melanocytic nevus of the oral cavity: a case report with emphasis on the surgical excision procedures

Minerva stomatologica

We report a case of a 37-year-old caucasian woman presenting a 1 cm pinkish nodular asymptomatic ... more We report a case of a 37-year-old caucasian woman presenting a 1 cm pinkish nodular asymptomatic lesion of the hard palate, slowly growing in the last years. The lesion underwent to biopsy. Histological analysis showed the nevus tissue layered under a continuous squamous epithelium. The stroma contained nests of medium-sized round cells, with regular monomorphous nuclei. The nevus cells were immunohistochemically positive for S-100 protein, while melanin, visualized by Masson-Fontana silver staining, was absent. Therefore a diagnosis of non pigmented melanocytic nevus was formulated. Because of its rarity and to avoid any risk of malignant transformation, a surgical treatment with wide excision was chosen; the surgical wound was previously covered with a membrane of fibrin and autologous platelets, and subsequently sutured, resulting in a total heal. This procedure seems to be the most reliable to approach melanocytic lesions of the oral cavity. Clinical diagnosis of non-pigmented n...

Research paper thumbnail of Alveolar bone regeneration in post-extraction socket: a review of materials to postpone dental implant

Bio-medical materials and engineering, 2011

Tooth extraction usually involves alveolar bone loss and reduction in height and width of the rem... more Tooth extraction usually involves alveolar bone loss and reduction in height and width of the remaining alveolar socket, owing to the physiological bone resorption. This occurrence may perform an inadequate bone profile, that make difficult orthodontic applications, compromising the functional and aesthetic restoration of dental implants. The present review will provide an update on the biological and clinical profile of materials currently in use and those under investigation, in the recovering of bone margins of edentulous sockets.

Research paper thumbnail of Surface oxidation of UHMWPE for orthopedic use increases apoptosis and necrosis in human granulocytes

Journal of materials science. Materials in medicine, 2003

Ultra high molecular weight polyethylene (UHMWPE) used in orthopedic prosthesis is often steriliz... more Ultra high molecular weight polyethylene (UHMWPE) used in orthopedic prosthesis is often sterilized with gamma-rays and the subsequent oxidation was suggested to favor the in vivo wear. UHMWPE debries produced by wearing trigger an inflammatory response that can led to the implant failure. To explore direct effects of UHMWPE oxidation on immunocompetent cells and their possible role in the prosthesis failure, peripheral blood cells (PBCs) have been grown for 24 and 48 h onto plastic (Ct), UHMWPE (PE) and heat oxidized UHMWPE (PEOx) discs. PBCs necrosis and apoptosis were assessed in flow cytometry using propidium iodide staining. After 24 h, no statistically significant differences were observed in the amount of apoptotic and necrotic cells between Ct, PE and PEOx samples while, after 48 h, both necrotic and apoptotic cells were strongly increased in PEOx samples where also the granulocytes population appeared strongly reduced (6.3+/-1.1%) compared to PE (10.5+/-1.5%) and Ct (15.1+/...

Research paper thumbnail of Effect of retinoic acid and vitamin D3 on osteoblast differentiation and activity in aging

Journal of Bone and Mineral Metabolism, 2015

analyzed (the proliferation, differentiation, and new matrix deposition are significantly reduced... more analyzed (the proliferation, differentiation, and new matrix deposition are significantly reduced in aged osteoblasts), with the exception of PPARγ 2 , which we found to be constitutively overexpressed and not modulated by retinoic acid or calcitriol administration. Our findings show the impaired ability of aged osteoblasts to perform adequate functional response and draw attention to the therapeutic approaches for bone healing in elderly patients.

Research paper thumbnail of Epiregulin induces human SK-N-BE cell differentiation through ERK1/2 signaling pathway

Growth Factors, 2013

Epidermal growth factor (EGF) and other EGF-related growth factors, such as transforming growth f... more Epidermal growth factor (EGF) and other EGF-related growth factors, such as transforming growth factor-a, are able to stimulate neuroblastoma (NB) cell proliferation. Epiregulin (Epi) is a growth factor belonging to the EGF family known to be more potent than EGF in mediating mitogenic signals. In this study, we tested the ability of Epi to stimulate a human NB cell line (SK-N-BE) proliferation. Surprisingly, Epi (50-1000 ng/ml) induced a reduction in SK-N-BE proliferation along with a morphological differentiation, associated with an increase in MMP-9 expression. Moreover, Epi-induced differentiation was inhibited by ERK1/2 phosphorilation inhibition. In conclusion, Epi could represent a novel and useful tool to oppose NB cell proliferation.

Research paper thumbnail of Neuro-immune modulation of the thymus microenvironment�(Review)

International Journal of Molecular Medicine, 2014

The thymus is the primary site for T-cell lymphopoiesis. Its function includes the maturation and... more The thymus is the primary site for T-cell lymphopoiesis. Its function includes the maturation and selection of antigen specific T cells and selective release of these cells to the periphery. These highly complex processes require precise parenchymal organization and compartmentation where a plethora of signalling pathways occur, performing strict control on the maturation and selection processes of T lymphocytes. In this review, the main morphological characteristics of the thymus microenvironment, with particular emphasis on nerve fibers and neuropeptides were assessed, as both are responsible for neuro-immune-modulation functions. Among several neurotransmitters that affect thymus function, we highlight the dopaminergic system as only recently has its importance on thymus function and lymphocyte physiology come to light.

Research paper thumbnail of Dopamine D1-D5 receptor protein immunohistochemistry in dog pial arteries

The Journal of Headache and Pain, 2000

The localization of dopamine D1-D5 receptor protein was investigated in different sized dog pial ... more The localization of dopamine D1-D5 receptor protein was investigated in different sized dog pial arteries. This was done to further understand the pathophysiology of cerebrovascular dopaminergic system in migraine. The study was performed in sections of dog brain including the pia-arachnoid membrane, which were processed for indirect immunohistochemistry using antibodies raised against dopamine D1-D5 receptor protein. A faint dopamine D1

Research paper thumbnail of Effect of in vitro mechanical compression on Epilysin (matrix metalloproteinase-28) expression in hypertrophic scars

Wound Repair and Regeneration, 2005

Epilysin, designated matrix metalloproteinase (MMP)-28, is the newest member of this family of pr... more Epilysin, designated matrix metalloproteinase (MMP)-28, is the newest member of this family of proteases expressed by keratinocytes in response to an injury. MMP-28 0 s physiological role and specific substrates are unknown, but its expression pattern suggests that it may serve a role in both tissue homeostasis and wound healing. The aim of this preliminary study was to observe the presence of MMP-28 protein in normotrophic and hypertrophic scars and to evaluate the effect of in vitro mechanical compression on its expression. Biopsies from normotrophic and hypertrophic scars resulting from burns were divided into two samples, one to be used as control (uncompressed) and the other to be compressed in an oxygenated organ chamber for 24 hours in the presence of a serum-free medium, using an electromechanical load transducer (stable pressure ¼ 35 mmHg). Analysis of MMP-28 protein secretion, assessed by Western blot and b-casein zymography in scar conditioned media, revealed that normotrophic scar did not release MMP-28 in any condition while hypertrophic scar released active MMP-28 both in control conditions and after compression. MMP-28

Research paper thumbnail of Neuropeptides of human thymus in normal and pathological conditions

Peptides, 2011

Human thymus of healthy subjects and patients affected by thymoma-associated Myastenia Gravis wer... more Human thymus of healthy subjects and patients affected by thymoma-associated Myastenia Gravis were studied in order to visualize and compare the morphological distributive pattern of four neuropeptides: vasoactive intestinal peptide, substance P, neuropeptide Y, and neurotensin. Based on our observations, we formulated hypotheses on their relations in neuro-immunomodulation under physiological and pathophysiological conditions. Immuno-histochemical staining for neuropeptides was performed and morphological and morphometrical analyses were conducted on healthy and diseased thymus. In normal thymus, a specific distributive pattern was observed for the several neuropeptide-positive nerves in different thymus lobular zones. In particular substance P-positive fibers were observed in subcapsular zone, specifically located into parenchyma, where they represent the almost total amount of fibers; neurotensin-positive fibers were observed primarily located in parenchyma than perivascular site of several thymus lobular zones, and more abundant the cortico-medullary and medullary zones. Instead VIP- and NPY-positive fibers were widely distributed in perivascular and parenchymal sites of several thymus lobular zones. In thymoma, the distribution of neuropeptide-positive fibers was quantitatively reduced, while cells immunopositive to VIP and substance P were quantitatively increased and dispersed. Observation of the perivascular and parenchymal distribution of the analyzed neuropeptides suggests evidence that a regulatory function is performed by nerves and cells that secrete neuropeptide into the thymus. The alteration of neuropeptide patterns in thymoma suggests that these neurotransmitters play a role in autoimmune diseases such as Myastenia Gravis.

Research paper thumbnail of J Tissue Eng.pdf

Creative Commons Non Commercial CC-BY-NC: This article is distributed under the terms of the Crea... more Creative Commons Non Commercial CC-BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).

Research paper thumbnail of Journal of Bone and Mineral Metabolism Effect of retinoic acid and vitamin D 3 on osteoblast differentiation and activity in aging

analyzed (the proliferation, differentiation, and new matrix deposition are significantly reduced... more analyzed (the proliferation, differentiation, and new matrix deposition are significantly reduced in aged osteoblasts), with the exception of PPARγ 2 , which we found to be constitutively overexpressed and not modulated by retinoic acid or calcitriol administration. Our findings show the impaired ability of aged osteoblasts to perform adequate functional response and draw attention to the therapeutic approaches for bone healing in elderly patients.

Research paper thumbnail of In vitro mechanical compression induces apoptosis and regulates cytokines release in hypertrophic scars

Wound Repair and Regeneration, 2003

Hypertrophic scars resulting from severe burns are usually treated by continuous elastic compress... more Hypertrophic scars resulting from severe burns are usually treated by continuous elastic compression. Although pressure therapy reaches success rates of 60-85% its mechanisms of action are still poorly understood. In this study, apoptosis induction and release of interleukin-1b (IL-1b) and tumor necrosis factor-a (TNF-a) were evaluated in normal (n ¼ 3) and hypertrophic (¼7) scars from burns after in vitro mechanical compression. In the absence of compression (basal condition) apoptotic cells, scored using terminal deoxyribonucleotidyl transferase assay, were present after 24 hours in the derma of both normal scar (23 ± 0.4% of total cell) and hypertrophic scar (11.3 ± 1.4%). Mechanical compression (constant pressure of 35 mmHg for 24 hours) increased apoptotic cell percentage both in normal scar (29.5 ± 0.4%) and hypertrophic scar (29 ± 1.7%). IL-1b released in the medium was undetectable in normal scar under basal conditions while in hypertrophic scar the IL-1b concentration was 3.48 ± 0.2 ng/g. Compression in hypertrophic scar-induced secretion of IL-1b twofold higher compared to basal condition. (7.72 ± 0.2 ng/g). TNF-a basal concentration measured in normal scar medium was 8.52 ± 4.01 ng/g and compression did not altered TNF-a release (12.86 ± 7.84 ng/g). TNF-a basal release was significantly higher in hypertrophic scar (14.74 ± 1.42 ng/g) compared to normal scar samples and TNF-a secretion was diminished (3.52 ± 0.97 ng/g) after compression. In conclusion, in our in vitro model, mechanical compression resembling the clinical use of elastocompression was able to strongly increase apoptosis in the hypertrophic scar derma as observed during granulation tissue regression in normal wound healing. Moreover, the observed modulation of IL-1b and TNF-a release by mechanical loading could play a key role in hypertrophy regression induced by elastocompression. (WOUND REP REG 2003;11:331-336) Hypertrophic scars (HSs) are the result of alterations in the normal processes of cutaneous wound healing occurring as a consequence of injury of the skin, especially burns. HSs are characterized by excessive deposition of fibroblast-derived extracellular matrix (ECM) proteins, especially collagen, in the derma over long periods of time, 1 by persistent inflammation and by fibrosis. 2 The disregulation of ECM turnover observed in the HS seems to be related to an excessive and persistent synthesis of pro-inflammatory/ fibrogenic cytokines such as interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), platelet derived growth factor and transforming growth factor-b from inflammatory cells. In fact, immunohistochemical analysis of HS cytokine expression has shown that transforming growth factor-b , IL-6 and TNFb are comparable to normal scar (NS), while ECM Extracellular matrix ELISA Enzyme-linked immunosorbent assay HS Hypertrophic scar IL-1b Interleukin-1b NS Normal scar PBS Phosphate buffered saline solution PGE 2 Prostaglandin E 2 TdT Terminal deoxyribonucleotidyl transferase TNF-a Tumor necrosis factor-a From the

Research paper thumbnail of Muscarinic Cholinergic Receptors and Acetylcholinesterase Activity in Umbilical Artery and Vein in Pregnancy-Induced Hypertension (Pre-Eclampsia)

Clinical and Experimental Hypertension, 1997

The influence of pregnancy-induced hypertension (pre-eclampsia) on muscarinic cholinergic recepto... more The influence of pregnancy-induced hypertension (pre-eclampsia) on muscarinic cholinergic receptors and on acetylcholinesterase (AChE) activity was investigated using frozen sections of the umbilical artery and vein. Pre-eclamptic patients undergoing Caesarean delivery and normotensive pregnant control woman undergoing Caesarean delivery with similar parity, gestation length and age were examined. Muscarinic cholinergic receptors were assayed in frozen sections of the umbilical artery and vein by a radioligand binding assay technique, using [3H]-N-methyl scopolamine (NMS) as a ligand. AChE was demonstrated with a histochemical technique associated with microdensitometry. [3H]-NMS was specifically bound to sections of both umbilical artery and vein in a manner consistent with the labelling of muscarinic cholinergic receptors. The affinity of the radioligand was similar in the two vessels, whereas the maximum density of binding sites (Bmax) was higher in the umbilical vein than in the artery. A faint AChE reactivity was observed in the tunica media of both umbilical artery and vein. In pre-eclampsia, a loss of [3H]-NMS binding sites not accompanied by changes in the affinity of radioligand was found. The decrease of muscarinic cholinergic receptors involved to a greater extent the umbilical artery than the vein. No differences in AChE activity were found at the level of umbilical artery and vein between control and pre-eclamptic subjects. These findings suggest that pre-eclampsia is characterized by a loss of muscarinic cholinergic receptors in the umbilical circulation not accompanied by changes of the acetylcholine catabolizing enzyme AChE. It is possible that the decreased density of vascular muscarinic cholinergic receptors in pregnancy-induced hypertension contribute to the increased resistance of the umbilical circulation occurring in pre-eclampsia.

Research paper thumbnail of Activation of caspase-8 triggers anoikis in human neuroblastoma cells

Neuroscience Research, 2006

Cells require appropriate interaction with extracellular matrix proteins mediated by integrins to... more Cells require appropriate interaction with extracellular matrix proteins mediated by integrins to grow, differentiate and survive. Many cell types including nervous cells undergo anoikis, a substrate-dependent apoptosis, when adhesion is impaired. Resistance of tumors to cytotoxic drugs is probably due to disturbed apoptosis programs. The proteolytic enzymes caspases are the main executioners of apoptosis. It was reported that caspase-8 expression is deficient in some neuroblastoma cells. We demonstrated that human neuroblastoma cell line SK-B-BE, differentiated with retinoic acid, expressed caspases 3, 8 and 9. Caspases 8 and 3, but not caspase-9 were activated in SK-N-BE cells cultured in suspension or on aspecific adhesive substrate. Cell positive to caspase-8 were classified into four stages, by morphometric and densitometric parameters. The use of the specific caspase-8 inhibitor Z-IETD-FMK dramatically reduced apoptosis, demonstrating that caspase-8 is the upstream initiator caspase during SK-N-BE cells anoikis. Among matrix proteins, type I collagen is the most effective and fibronectin the least in delaying anoikis. The activation of caspases 8 and 3 by unligated integrins was dependent on the state of neuronal differentiation, since the most differentiated cell was the most vulnerable to anoikis. These data show that activation of caspase-8 is specifically required to promote anoikis in SK-N-BE neuroblastoma cells.

Research paper thumbnail of Effect of the thyrotropin releasing hormone analogue posatirelin (RGH 2202) on microanatomical changes induced by lesions of the nucleus basalis magnocellularis in the rat

Drugs under experimental and clinical research

The effect of 4 and 8 weeks treatment with 10 mg/kg/day of the thyrotropin releasing hormone anal... more The effect of 4 and 8 weeks treatment with 10 mg/kg/day of the thyrotropin releasing hormone analogue posatirelin (L-6-ketopiperidine-2-carbonyl-L-leucyl-proline amide) on microanatomical changes induced by monolateral and bilateral lesions of the nucleus basalis magnocellularis (NBM) were investigated. The following parameters were assessed in the frontal cortex and hippocampus of NBM-lesioned and sham-operated rats: 1) number of nerve cell and glial fibrillary acidic protein (GFAP)-immunoreactive astrocyte profiles; 2) density of silver-gold impregnated fibres; 3) density of choline acetyltransferase (ChAT)-immunoreactive fibres; 4) intensity of acetylcholinesterase (AChE) staining. In NBM-lesioned untreated rats, no changes in the number of nerve cell or of astrocyte profiles were found either in the frontal cortex or in the hippocampus. The only exception was a decrease in the number of granule neuron profiles in the dentate gyrus at 8 weeks after lesioning. Silver-gold impregnated fibres, which express the width of interneuronal connections, were reduced in the hippocampus but not in the frontal cortex of NBM-lesioned rats. ChAT immunoreactivity and AChE reactivity, which were localised respectively in nerve fibre-like structures and in the neuropil, were decreased in the frontal cortex but not in the hippocampus from the fourth week after NBM lesioning. Lesions did not change the number of ChAT-immunoreactive nerve fibres or intensity of AChE staining in the hippocampus. Treatment with posatirelin was without effect on the number of nerve cell profiles or of GFAP-immunoreactive astrocytes both at 4 and 8 weeks after NBM lesioning. Treatment with the compound increased the number of silver-gold impregnated fibres in the hippocampus of NBM-lesioned rats and restored in part ChAT immunoreactivity and AChE reactivity in the frontal cortex. These effects were noticeable in NBM-lesioned rats after 8 weeks of treatment. The possible significance of the neuroprotective effect elicited by posatirelin treatment after lesions of the NBM is discussed.

Research paper thumbnail of Effect of treatment with the neuroactive peptide posatirelin on microanatomical changes of frontal cortex and hippocampus caused by lesions of the locus coeruleus

Drugs under experimental and clinical research

The influence of monolateral and bilateral lesions of the Locus coeruleus (LC) on the number of n... more The influence of monolateral and bilateral lesions of the Locus coeruleus (LC) on the number of nerve cell and glial fibrillary acidic protein (GFAP)-immunoreactive astrocyte profiles, on silver-gold impregnated fibres and on tyrosine hydroxylase (TH) immunoreactivity was assessed in the rat frontal cortex and hippocampus. The influence of treatment for 4 and 8 weeks with a 10 mg/kg/day dose of the neuroactive peptide posatirelin on the above parameters was also investigated. Lesions of the LC decreased the number of nerve cell profiles in the frontal cortex 8 weeks after lesioning and were without effect on nerve cell profiles in the frontal cortex 4 weeks after lesioning and in the hippocampus at both 4 and 8 weeks after LC lesioning. Glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes were not affected by lesions of LC. Silver-gold impregnated fibres were decreased in the frontal cortex but not in the hippocampus of LC-lesioned rats at 8 weeks after lesioning. TH immunoreactivity, which was localized in nerve fibre-like structures both in the frontal cortex and in the hippocampus was decreased in the frontal cortex and in the hippocampus from the 4th week after LC lesioning. Treatment with posatirelin was without effect on the number of nerve cell and of GFAP-immunoreactive astrocyte profiles at both 4 and 8 weeks after LC lesioning, with the exception of nerve cells of the frontal cortex in monolaterally-lesioned rats which were increased 8 weeks after lesioning. The compound increased silver-gold impregnated fibres in the frontal cortex of monolaterally lesioned rats after 8 weeks of treatment, but did not affect TH immunoreactivity both in the frontal cortex or in the hippocampus. The above results suggest that treatment with posatirelin exerts a neuroprotective effect on the frontal cortex consisting of the partial restoration of some microanatomical changes caused by lesions of LC. The possible significance of this effect is discussed.

Research paper thumbnail of Nephroprotective effect of treatment with calcium channel blockers in spontaneously hypertensive rats

Journal of Pharmacology and Experimental Therapeutics

The influence of hypertension and of treatment with some dihydropyridine-type Ca(2+) channel bloc... more The influence of hypertension and of treatment with some dihydropyridine-type Ca(2+) channel blockers and with the nondihydropyridine-type vasodilator hydralazine on the morphology of kidney was investigated in 26-week-old spontaneously hypertensive rats (SHR) and in age-matched Wistar-Kyoto rats. Fourteen-week-old SHR were treated for 12 weeks with a nonhypotensive dose of lercanidipine or with equihypotensive doses of lercanidipine, manidipine, nicardipine, and hydralazine. In control SHR, systolic pressure values were significantly higher in comparison with Wistar-Kyoto rats. Treatment with the low dose of lercanidipine did not reduce systolic blood pressure in SHR, whereas the higher dose of lercanidipine or other compounds tested significantly decreased systolic pressure values. Glomerular hypertrophy accompanied by signs of glomerulosclerosis, increase of mesangial cells, and convoluted tubules degeneration were observed in control SHR. Hypotensive doses of Ca(2+) antagonists countered glomerular injury, the increase of mesangial cells, the reduction of capsular space, and tubular degeneration. Hydralazine, in spite of its hypotensive activity, displayed a slight nephroprotective action. The nonhypotensive dose of lercanidipine countered in part glomerular injury, narrowing of capsular space, and tubular degeneration, and decreased mesangial cell augmentation in SHR. These results suggest that treatment with dihydropyridine-type Ca(+2) antagonists counters hypertensive glomerular and tubular changes occurring in SHR. The demonstration of nephroprotection by the nonhypotensive dose of lercanidipine suggests that the renal effects of the compound may be in part unrelated to its hemodynamic activity.

Research paper thumbnail of Seminar on Hypertension and Brain Damage - Preface

Clinical and Experimental Hypertension

Research paper thumbnail of T-cell subpopulations express a different pattern of dopaminergic markers in intra- and extra-thymic compartments

Journal of biological regulators and homeostatic agents

An involvement of dopamine in regulation of the immune function has been assessed and dopaminergi... more An involvement of dopamine in regulation of the immune function has been assessed and dopaminergic system has been found widely represented in thymus. Nevertheless detail on the characterization of dopaminergic system in assisting thymocytes development and lymphocytes mature physiology are still lacking. The present study was designed to characterize dopamine plasma membrane transporter (DAT), vesicular dopamine transporters (VMAT)-1 and -2, and dopamine D1-like and D2-like receptors in rat thymocytes, splenocytes and peripheral blood mononuclear cells. Western blot and RT-PCR analyses, performed on these cells, showed an expression of dopamine transporters and receptors during thymocyte development (when of CD4 and CD8 markers are differently expressed). Furthermore FACS analysis, indicates that DAT and dopamine D1-like receptors are expressed at high levels in thymocytes, splenocytes, and peripheral lymphocytes. The percentage of CD4+ CD8+ (double-positive) thymocytes expressing ...

Research paper thumbnail of Pharmaco-epidemiological description of the population of the Marche Region (central Italy) treated with the antipsychotic drug olanzapine

Annali dell'Istituto superiore di sanità, 2013

In Italy, even though olanzapine has been discouraged for treatment of behaviour disorders in old... more In Italy, even though olanzapine has been discouraged for treatment of behaviour disorders in older patients affected by dementia, some physicians chose to prescribe for them. In response to this situation, the Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA) promulgated a cautionary note. This study examined epidemiological indices for olanzapine prescriptions between 2004 and 2007 in the Marche Region of central Italy and in its provinces, to assess physician compliance with the AIFA note, and to determine whether there were differences in drug prescription between populations of the same territory, or differences based on gender or age group. Our analyses revealed high olanzapine use among young men and mature women, suggesting that these groups are most prone to psychotic symptoms. Analysis revealed that olanzapine prescription in elderly patients was reduced in some provinces, in line with the AIFA note. Prudent use of olanzapine prescription, in compliance with the AIF...

Research paper thumbnail of Non pigmented melanocytic nevus of the oral cavity: a case report with emphasis on the surgical excision procedures

Minerva stomatologica

We report a case of a 37-year-old caucasian woman presenting a 1 cm pinkish nodular asymptomatic ... more We report a case of a 37-year-old caucasian woman presenting a 1 cm pinkish nodular asymptomatic lesion of the hard palate, slowly growing in the last years. The lesion underwent to biopsy. Histological analysis showed the nevus tissue layered under a continuous squamous epithelium. The stroma contained nests of medium-sized round cells, with regular monomorphous nuclei. The nevus cells were immunohistochemically positive for S-100 protein, while melanin, visualized by Masson-Fontana silver staining, was absent. Therefore a diagnosis of non pigmented melanocytic nevus was formulated. Because of its rarity and to avoid any risk of malignant transformation, a surgical treatment with wide excision was chosen; the surgical wound was previously covered with a membrane of fibrin and autologous platelets, and subsequently sutured, resulting in a total heal. This procedure seems to be the most reliable to approach melanocytic lesions of the oral cavity. Clinical diagnosis of non-pigmented n...

Research paper thumbnail of Alveolar bone regeneration in post-extraction socket: a review of materials to postpone dental implant

Bio-medical materials and engineering, 2011

Tooth extraction usually involves alveolar bone loss and reduction in height and width of the rem... more Tooth extraction usually involves alveolar bone loss and reduction in height and width of the remaining alveolar socket, owing to the physiological bone resorption. This occurrence may perform an inadequate bone profile, that make difficult orthodontic applications, compromising the functional and aesthetic restoration of dental implants. The present review will provide an update on the biological and clinical profile of materials currently in use and those under investigation, in the recovering of bone margins of edentulous sockets.

Research paper thumbnail of Surface oxidation of UHMWPE for orthopedic use increases apoptosis and necrosis in human granulocytes

Journal of materials science. Materials in medicine, 2003

Ultra high molecular weight polyethylene (UHMWPE) used in orthopedic prosthesis is often steriliz... more Ultra high molecular weight polyethylene (UHMWPE) used in orthopedic prosthesis is often sterilized with gamma-rays and the subsequent oxidation was suggested to favor the in vivo wear. UHMWPE debries produced by wearing trigger an inflammatory response that can led to the implant failure. To explore direct effects of UHMWPE oxidation on immunocompetent cells and their possible role in the prosthesis failure, peripheral blood cells (PBCs) have been grown for 24 and 48 h onto plastic (Ct), UHMWPE (PE) and heat oxidized UHMWPE (PEOx) discs. PBCs necrosis and apoptosis were assessed in flow cytometry using propidium iodide staining. After 24 h, no statistically significant differences were observed in the amount of apoptotic and necrotic cells between Ct, PE and PEOx samples while, after 48 h, both necrotic and apoptotic cells were strongly increased in PEOx samples where also the granulocytes population appeared strongly reduced (6.3+/-1.1%) compared to PE (10.5+/-1.5%) and Ct (15.1+/...

Research paper thumbnail of Effect of retinoic acid and vitamin D3 on osteoblast differentiation and activity in aging

Journal of Bone and Mineral Metabolism, 2015

analyzed (the proliferation, differentiation, and new matrix deposition are significantly reduced... more analyzed (the proliferation, differentiation, and new matrix deposition are significantly reduced in aged osteoblasts), with the exception of PPARγ 2 , which we found to be constitutively overexpressed and not modulated by retinoic acid or calcitriol administration. Our findings show the impaired ability of aged osteoblasts to perform adequate functional response and draw attention to the therapeutic approaches for bone healing in elderly patients.

Research paper thumbnail of Epiregulin induces human SK-N-BE cell differentiation through ERK1/2 signaling pathway

Growth Factors, 2013

Epidermal growth factor (EGF) and other EGF-related growth factors, such as transforming growth f... more Epidermal growth factor (EGF) and other EGF-related growth factors, such as transforming growth factor-a, are able to stimulate neuroblastoma (NB) cell proliferation. Epiregulin (Epi) is a growth factor belonging to the EGF family known to be more potent than EGF in mediating mitogenic signals. In this study, we tested the ability of Epi to stimulate a human NB cell line (SK-N-BE) proliferation. Surprisingly, Epi (50-1000 ng/ml) induced a reduction in SK-N-BE proliferation along with a morphological differentiation, associated with an increase in MMP-9 expression. Moreover, Epi-induced differentiation was inhibited by ERK1/2 phosphorilation inhibition. In conclusion, Epi could represent a novel and useful tool to oppose NB cell proliferation.

Research paper thumbnail of Neuro-immune modulation of the thymus microenvironment�(Review)

International Journal of Molecular Medicine, 2014

The thymus is the primary site for T-cell lymphopoiesis. Its function includes the maturation and... more The thymus is the primary site for T-cell lymphopoiesis. Its function includes the maturation and selection of antigen specific T cells and selective release of these cells to the periphery. These highly complex processes require precise parenchymal organization and compartmentation where a plethora of signalling pathways occur, performing strict control on the maturation and selection processes of T lymphocytes. In this review, the main morphological characteristics of the thymus microenvironment, with particular emphasis on nerve fibers and neuropeptides were assessed, as both are responsible for neuro-immune-modulation functions. Among several neurotransmitters that affect thymus function, we highlight the dopaminergic system as only recently has its importance on thymus function and lymphocyte physiology come to light.

Research paper thumbnail of Dopamine D1-D5 receptor protein immunohistochemistry in dog pial arteries

The Journal of Headache and Pain, 2000

The localization of dopamine D1-D5 receptor protein was investigated in different sized dog pial ... more The localization of dopamine D1-D5 receptor protein was investigated in different sized dog pial arteries. This was done to further understand the pathophysiology of cerebrovascular dopaminergic system in migraine. The study was performed in sections of dog brain including the pia-arachnoid membrane, which were processed for indirect immunohistochemistry using antibodies raised against dopamine D1-D5 receptor protein. A faint dopamine D1

Research paper thumbnail of Effect of in vitro mechanical compression on Epilysin (matrix metalloproteinase-28) expression in hypertrophic scars

Wound Repair and Regeneration, 2005

Epilysin, designated matrix metalloproteinase (MMP)-28, is the newest member of this family of pr... more Epilysin, designated matrix metalloproteinase (MMP)-28, is the newest member of this family of proteases expressed by keratinocytes in response to an injury. MMP-28 0 s physiological role and specific substrates are unknown, but its expression pattern suggests that it may serve a role in both tissue homeostasis and wound healing. The aim of this preliminary study was to observe the presence of MMP-28 protein in normotrophic and hypertrophic scars and to evaluate the effect of in vitro mechanical compression on its expression. Biopsies from normotrophic and hypertrophic scars resulting from burns were divided into two samples, one to be used as control (uncompressed) and the other to be compressed in an oxygenated organ chamber for 24 hours in the presence of a serum-free medium, using an electromechanical load transducer (stable pressure ¼ 35 mmHg). Analysis of MMP-28 protein secretion, assessed by Western blot and b-casein zymography in scar conditioned media, revealed that normotrophic scar did not release MMP-28 in any condition while hypertrophic scar released active MMP-28 both in control conditions and after compression. MMP-28

Research paper thumbnail of Neuropeptides of human thymus in normal and pathological conditions

Peptides, 2011

Human thymus of healthy subjects and patients affected by thymoma-associated Myastenia Gravis wer... more Human thymus of healthy subjects and patients affected by thymoma-associated Myastenia Gravis were studied in order to visualize and compare the morphological distributive pattern of four neuropeptides: vasoactive intestinal peptide, substance P, neuropeptide Y, and neurotensin. Based on our observations, we formulated hypotheses on their relations in neuro-immunomodulation under physiological and pathophysiological conditions. Immuno-histochemical staining for neuropeptides was performed and morphological and morphometrical analyses were conducted on healthy and diseased thymus. In normal thymus, a specific distributive pattern was observed for the several neuropeptide-positive nerves in different thymus lobular zones. In particular substance P-positive fibers were observed in subcapsular zone, specifically located into parenchyma, where they represent the almost total amount of fibers; neurotensin-positive fibers were observed primarily located in parenchyma than perivascular site of several thymus lobular zones, and more abundant the cortico-medullary and medullary zones. Instead VIP- and NPY-positive fibers were widely distributed in perivascular and parenchymal sites of several thymus lobular zones. In thymoma, the distribution of neuropeptide-positive fibers was quantitatively reduced, while cells immunopositive to VIP and substance P were quantitatively increased and dispersed. Observation of the perivascular and parenchymal distribution of the analyzed neuropeptides suggests evidence that a regulatory function is performed by nerves and cells that secrete neuropeptide into the thymus. The alteration of neuropeptide patterns in thymoma suggests that these neurotransmitters play a role in autoimmune diseases such as Myastenia Gravis.