Mirca Marini

University of Florence, Florens, Tuscany, Italy

Are you Mirca Marini?

Claim your profile

Publications (55)162.85 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Regular and structured physical activity is known to be effective in preventing and/or reducing the physical and mental decline associated with aging. Indeed, such usefulness of physical activity has been associated with the concept of "successful aging". The aim of the present study was to evaluate the possible physical and cognitive effects deriving from the practice of DanceSport in comparison with the participation in adapted physical activity (APA) programs and sedentarity.
    The Journal of sports medicine and physical fitness. 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Restoration of functions in Huntington's disease (HD) by neurotransplantation stems from the formation of a striatum-like structure capable of establishing host connections as a result of grafted striatal neuroblast maturation. For the first time, we demonstrated some developmental steps accomplished by progenitor cells in the brain of an HD patient and analysed the molecular asset of the human primordium. Case Report: Surgery involved bilateral (two sessions) stereotactic, caudate-putaminal transplantation of whole ganglionic eminence fragments from single legally aborted fetuses. MRI showed that the tissue deposits of the left hemisphere grew and joined to constitute a single tissue mass that remodelled basal ganglia anatomy and remained stable in size over time. No evidence of graft growth was observed contralaterally. PET demonstrated increased striatal and stable cortical metabolism. Unified Huntington's Disease Rating Scale assessments demonstrated improvement of motor performances, which faded over the 36-month follow-up. Cognitive performance tended to decrease at a lower rate than before transplantation. Conclusion: The striatal primordium grew into the host brain and this process was associated with metabolic change and some clinical benefit. The study suggests the plasticity and reparative potential of un-manipulated primordium in an era where promising cell-based therapies are still in their infancy. © 2014 S. Karger AG, Basel.
    Stereotactic and Functional Neurosurgery 07/2014; 92(4):211-217. · 1.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Grafting fetal striatal cells into the brain of Huntington's disease (HD) patients has raised certain expectations in the past decade as an effective cell-based-therapy for this devastating condition. We argue that the first requirement for successful transplantation is defining the window of plasticity for the striatum during development when the progenitor cells, isolated from their environment, are able to maintain regional-specific-identity and to respond appropriately to cues. The primary cell culture from human fetal striatal primordium described here consist of a mixed population of neural stem cells, neuronal-restricted progenitors and striatal neurons. These cells express trophic factors, such as BDNF and FGF2. We show that these neurotrophins maintain cell plasticity, inducing the expression of neuronal precursor markers and cell adhesion molecules, as well as promoting neurogenesis, migration and survival. We propose that BDNF and FGF2 play an important autocrine-paracrine role during early striatum development in vivo and that their release by fetal striatal grafts may be relevant in the setting of HD cell therapy.
    Experimental Neurology 04/2014; · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Investigations mostly in animal models have shown a role of sialic acid in the morphology and functionality of skeletal muscle during development and adult life. Several studies in humans have been performed regarding changes in sialic acid expression in a particular pathology, hereditary inclusion body myopathy, leading to muscular weakness and atrophy, with a similar phenomenon appearing also in sarcopenia of aging. In this study the expression of monomeric and polymeric sialic acids was evaluated in human skeletal muscle during adult life. Surgical biopsies of the Quadriceps femoris muscle from men aged 18-25 years (young group; n=8) and men aged 72-78 (elderly group; n=10) were collected for analysis. Expression of sialic acids was evaluated using lectin histochemistry, associated with enzymatic and chemical treatments to characterize monomeric and polymeric sialic acids. The polysialic acid expression was also evaluated by immunohistochemistry. Various types of sialic acid in the muscle tissue, in different amounts in the study groups, were detected. Monomeric sialic acids decreased in the elderly group compared with the young group, whereas polysialic acid increased. Sialic acid acetylation was present only in the young group. These findings demonstrated that changes in the expression of sialic acids in skeletal muscle tissue may be related to morphofunctional modifications occurring during aging.
    Acta histochemica 04/2014; · 1.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rabbits with high fat diet (HFD)-induced metabolic syndrome (MetS) developed hypogonadotropic hypogonadism (HH) and showed a reduced gonadotropin-releasing hormone (GnRH) immunopositivity in the hypothalamus. This study investigated the relationship between MetS and hypothalamic alterations in HFD-rabbits. Gonadotropin levels decreased as a function of MetS severity, hypothalamic gene expression of glucose transporter 4 (GLUT4) and interleukin-6 (IL-6). HFD determined a low-grade inflammation in the hypothalamus, significantly inducing microglial activation, expression and immunopositivity of IL-6, as well as GLUT4 and reduced immunopositivity for KISS1 receptor, whose mRNA expression was negatively correlated to glucose intolerance. Correcting glucose metabolism with obetcholic acid improved hypothalamic alterations, reducing GLUT4 and IL-6 immunopositivity and significantly increasing GnRH mRNA, without, however, preventing HFD-related HH. No significant effects at the hypothalamic level were observed after systemic anti-inflammatory treatment (infliximab). Our results suggest that HFD-induced metabolic derangements negatively affects GnRH neuron function through an inflammatory injury at the hypothalamic level.
    Molecular and Cellular Endocrinology 09/2013; · 4.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate histologic and molecular changes in human keratoconic corneas after the procedure of transepithelial collagen cross-linking (CXL), without the removal of corneal epithelium. Experimental laboratory investigation. Thirty corneal buttons were examined, 18 of which were from patients affected by severe keratoconus and submitted to penetrating keratoplasty (PK). Among these, 8 were analyzed without any treatment, 4 were treated with transepithelial CXL 2 hours before PK, and 6 were treated with transepithelial CXL 3 months before PK. Twelve normal corneal buttons from healthy donors were used as controls. The corneal buttons were then evaluated by hematoxylin-eosin staining and by immunostaining with markers of epithelial junction proteins (ß-catenin and connexin 43), of stromal keratocytes (CD34), of apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL] assay), and of collagen type I fibers. The analysis of epithelial markers showed a clear defective expression in keratoconic corneas before and soon after the transepithelial CXL treatment, returning to normal in corneas analyzed 3 months after transepithelial CXL. The analysis of stroma components indicated a loss of keratocytes in the upper stroma of keratoconic corneas and a trend toward a normal situation 3 months after transepithelial CXL; similarly, collagen fibers appeared disorganized in keratoconus, while their pattern appears to be close to normal 3 months after treatment. Histologic and immunohistochemical findings on human keratoconic corneas showed the presence of biochemical and morphologic alterations in the epithelium and the upper stroma that are significantly improved 3 months after transepithelial CXL. However, further studies are necessary to assess to what extent these results correlate with measurable biomechanical effects.
    American Journal of Ophthalmology 08/2013; · 4.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Physical activity interventions are known to be effective in improving the physical and psychological complaints of breast cancer survivors. PURPOSE: To investigate the impact of a specific exercise training program on upper limb mobility and quality of life in breast cancer survivors. METHODS: The study included 55 women recruited at the Cancer Rehabilitation Centre in Florence after the completion of breast cancer treatment and rehabilitative physiotherapy. All participants underwent a 8-week specific exercise training to improve upper limb mobility function and quality of life. Anthropometric parameters were measured, and each subject underwent a battery of fitness tests to assess shoulder-arm mobility, range of motion, and back flexibility before and after specific exercise program. All participants filled out the Short Form-12 and numerical rating scale questionnaires to assess the quality of life and to quantify back and shoulder pain intensity. RESULTS: The evaluation of shoulder-arm mobility and self-reported questionnaire data revealed a statistically significant improvement after completion of our specific exercise program. CONCLUSION: An organized specific program of adapted physical activity can be effective in reducing the main adverse effects of surgery and oncological therapy, and may significantly improve shoulder-arm mobility and quality of life in breast cancer survivors.
    Journal of Physical Activity and Health 04/2013; · 1.95 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: During development the vertebrate skeleton is the product of deriving cells from distinct embryonic lineages. The craniofacial skeleton is formed by migrating cranial neural crest cells, whereas the axial and limb skeletons are derived from mesodermal cells. The Vascular Endothelial Growth Factors (VEGFs) / receptors (VEGFRs) system plays an important role in angiogenesis, as well as osteogenesis, during bone development, growth, and remodeling, attracting endothelial cells and osteoclasts and stimulating osteoblast differentiation. Recent evidence has shown that during development VEGFR-3 is also expressed in neural and glial precursors of forebrain and cerebellum, as well as in the eye. In this study, we found that VEGFR-1, VEGFR-2 and VEGFR-3 are expressed in human bone both in fetal and adult life. The gene expression levels were significantly higher in fetal samples especially in mandibles. In addition, higher levels of VEGFR-3 in orofacial district were confirmed by western blotting analysis. We also observed that in fetal mandibular samples VEGFRs colocalized in several osteoblasts, osteoclasts and osteoprogenitor cells. Furthermore, some cells coexpressed VEGFR-3 and ET-1, a marker of neural crest cells. The results demonstrated different expression of VEGFRs in human mandibular and femoral bones which could be correlated to their different structure, function and development during organogenesis. VEGFR-3 might represent a specific signal for ectomesenchymal lineage differentiation during early human development.
    Histology and histopathology 12/2012; 27(12):1579-87. · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose To evaluate the effects of transepithelial corneal crosslinking (TE-CXL) on epithelium and stroma in human corneasMethods Fifteen corneal buttons were examined. Ten were from patients with keratoconus submitted to penetrating keratoplasty (PKP). Five of them were treated with TE-CXL 2 hours before PKP, five of them were treated with TE-CXL 3 months before PKP. Five normal corneal buttons from healthy donors were used as controls. TE-CXL was performed with two different time of imbibition: 30 minutes and 2 hours.All samples were prepared for the detection of keratocyte apoptosis by TUNEL assay and for the morphological evaluation of epithelium and stroma by immunohistochemical analysis (Connexin 43, CD34).Results Normal corneas exhibited no TUNEL positive keratocytes while keratoconus and crosslinked samples showed moderate apoptotic cells in the anterior part of the stroma. Moreover, the samples treated with TE-CXL 2 hours before PKP showed also an almost completely deteriorated epithelium with TUNEL positive cells. The epithelial positivity for connexin43 (transmembrane protein that forms gap junction channels) was similar in the control and in the corneas with crosslinking 3 months before PKP, while seemed more scattered in the keratoconus. In the samples treated with TE-CXL 2 hours before PKP the positivity was patchy in the few remained epithelial cells.Conclusion The treatment with TE-CXL leads to epithelial damage and a reduction of keratocytes in the sub-epithelial region in the corneas treated 2 hours before PKP. In the samples treated with TE-CXL 3 months before PKP the positivity of both CD34 keratocytes and connexin-43 epithelial cells is similar to control.
    Acta ophthalmologica 09/2011; 89(s248). · 2.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effects of cadmium on the central nervous system are still relatively poorly understood and its role in neurodegenerative diseases has been debated. In our research, cultured explants from 25 human foetal spinal cords (10-11 weeks gestational age) were incubated with 10 and 100 μM cadmium chloride (CdCl(2)) for 24 h. After treatment, an immunohistochemical study [for Sglial fibrillary acidic protein (GFAP) and choline acetyltransferase (ChAT)], a Western blot analysis (for GFAP, β-Tubulin III, nerve growth factor receptor, Caspase 8 and poly (ADP-ribose) polymerase), and a terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL) assay (for detection of apoptotic bodies) were performed. The treatment with CdCl(2) induced a significant and dose-dependent change in the ratio motor neurons/glial cells in the ventral horns of human foetal spinal cord. The decrease of the choline acetyltransferase-positive cells (motor neurons) and the reduction of β Tubulin III indicate that CdCl(2) specifically affects motor neurons of the ventral horns. While the number of motor neurons decreased for the activation of apoptotic pathways (as shown by the increased expression of Caspase 8, nerve growth factor receptor, and poly (ADP-ribose) polymerase), glial cells, both in the subependymal zone and in the gray matter of the ventral horns, increased (as shown by the increase of GFAP expression). These results provide the evidence that during human spinal cord development, CdCl(2) may affect the fate of neural and glial cells thus, being potentially involved in the etiopathogenesis of neurodegenerative diseases.
    Biology of Metals 07/2011; 25(1):63-74. · 3.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the study was to investigate the content and distribution of sugar residues in placentas from pregnancies complicated by hypertensive disorders. Placentas from women with uncomplicated pregnancies (group 1), pregnancies complicated by gestational hypertension (group 2), pregnancies complicated by pre-eclampsia (group 3), pregnancies complicated by pre-eclampsia with HELLP syndrome (hemolysis, elevated liver enzymes and low platelets) (group 4) were collected. Lectins: ConA, WGA, PNA, SBA, DBA, UEA I, GNA, DSA, MAA, SNA, in combination with chemical and enzymatic treatments, were used. Data showed a decrease and/or lack of α-d-mannose, α-d-glucose and d-galactose-(β1-4)-N-acetyl-d-glucosamine in placentas from pre-eclampsia and pre-eclampsia with HELLP syndrome compared with control and hypertension cases. N-acetyl-d-galactosamine appeared and/or increased in placentas from hypertensive disorders. A different distribution of various types of sialic acid was observed in placentas from hypertensive disorders compared with the controls. In particular, placentas from pre-eclampsia, with and without HELLP syndrome, lacked the acetylated sialic acid side-chain. These findings demonstrate various alterations of the carbohydrate metabolism in the placentas from pregnancies complicated by different types of hypertensive disorders. This indicates correlation with the placental morpho-functional changes characteristic of these complications and with the degree of clinical severity.
    Acta histochemica 07/2011; 113(8):815-25. · 1.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Baseball, one of the most popular sports in the world, is a fast-moving sport that requires various motor abilities. Baseball is played also by blind subjects that participate in many other sports. In this study, we evaluated the role of the Italian modified version of baseball for blind subjects on balance. This modified version of baseball maintains the fast-moving characteristic ensuring the athlete safety. Forty total blind subjects were enrolled: 20 baseball athletes and 20 sedentary participants, as control. The balance was evaluated using the Fukuda Test and Tinetti Test, both in silence and in noise. This baseball game may help to improve the balance ability in blind subjects. The balance was significantly improved in blind athletes as compared with blind sedentary subjects. Given the peculiar characteristics of play, this modified version of baseball seems effective in improving various motor skills that, once transferred into daily activities, may significantly ameliorate the quality of life of blind subjects.
    The Journal of sports medicine and physical fitness 06/2011; 51(2):227-32. · 0.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study the characterization of various types of sugar residues in normal, keratoconus and cross-linked human corneas was performed using immunohistochemical localization with lectins. Corneal samples were collected and divided into three groups: (1) normal corneas from cadavers; (2) keratoconic corneal buttons; (3) keratoconic corneal buttons treated with cross-linking. A series of lectins including: DBA, SBA, PNA, ConA, WGA, UEA I, GNA, DSA, MAA, SNA, were used in combination with chemical and enzymatic treatments. Compared with the normal corneas, N-acetyl-D-glucosamine increased in the keratoconus corneas. L-fucose increased and/or appeared in the keratoconus and the cross-linked corneas. N-acetyl-D-galactosamine was more abundant in the epithelium of keratoconus corneas, but was lacking in the keratoconus and cross-linked endothelium. D-galactose-(β1-4)-N-acetyl-D-glucosamine was absent in the whole stroma of the keratoconus corneas and in the deep layers of the cross-linked ones. Sialic acids increased in the keratoconus corneas and decreased in the cross-linked ones. These results showed altered glycosylation in the keratoconic corneas and partially similar glycosylation in the cross-linked corneas, compared to the normal ones. This suggests a role played by sugar residues in maintaining the corneal structure. The changes could be related to structural alterations in keratoconus. The present findings contribute to our understanding of the effect of cross-linking treatment of keratoconic corneas in therapeutic attempts to re-establish the normal corneal structure.
    Acta histochemica 05/2011; 113(3):308-16. · 1.61 Impact Factor
  • ITALIAN JOURNAL OF ANATOMY AND EMBRYOLOGY; 01/2011
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic inflammation is now considered a determinant of benign prostatic hyperplasia (BPH), promoting, together with the hormonal milieu, prostate overgrowth and lower urinary tract symptoms (LUTS). Prostatic urethra actively participates in determining progression of LUTS associated with BPH. To investigate the expression of the vitamin D receptor (VDR) and the ability of the VDR agonist elocalcitol to reduce inflammatory responses in human prostatic urethra (hPU) cells. Human prostatic urethra, prostate and bladder neck were obtained from patients affected by BPH. Immunohistochemical studies for VDR expression were performed in tissue samples, from which primary cell cultures were also derived. In hPU cells, proliferation and chemiotaxis were studied, along with Rho kinase (ROCK) activity (MYPT-1 phosphorylation) by western blot. Quantitative RT-PCR was performed for VDR, cyclooxygenase (COX-2), and interleukin (IL)-8 expression. Urethra displays higher VDR expression compared to prostate and bladder neck tissues. The VDR agonist elocalcitol partially reverts COX-2 and IL-8 mRNA upregulation induced by a pro-inflammatory cytokine mixture (IL-17, interferon-γ, tumor necrosis factor-α) and inhibits cell migration in urethral cells. Elocalcitol prevents activation of ROCK, as previously demonstrated in bladder and prostate cell cultures. Our results suggest that prostatic urethra is, within the lower urinary tract, a novel target for VDR agonists, as shown by the capacity of elocalcitol to inhibit ROCK activity and to limit inflammatory responses in human primary urethra cells.
    Journal of endocrinological investigation 04/2010; 33(10):730-8. · 1.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the effects of corneal cross-linking on keratocytes and collagen fibres in human corneas. Fifteen corneal buttons were examined. Ten were from patients with keratoconus submitted to penetrating keratoplasty and five of them were treated with cross-linking 6 months before penetrating keratoplasty. Five normal corneal buttons from healthy donors were used as controls. All samples were prepared for TUNEL assay and Western blot analysis for the detection of keratocyte apoptosis and immunohistochemical analysis for the morphological evaluation of keratocytes and collagen fibre diameter. Normal corneas exhibited no TUNEL-positive keratocytes and keratoconic and cross-linked corneas showed moderate apoptotic cells mainly in the anterior part of the stroma. This apoptotic trend was confirmed by the cleavage of poly (ADP-ribose) polymerase assessed using Western blot. The Ki-67 staining showed a significant increase in the keratocyte proliferation in cross-linked corneas compared with normal and keratoconus. In cross-linked corneas CD34-positive keratocytes were regularly distributed throughout the whole corneal stroma as in the control, and keratoconus was associated with patchy loss of immunoreactivity. The immunohistochemical analysis of collagen type I showed a significant increase in fibre diameter of cross-linked corneas compared with control and keratoconus. Corneal cross-linking leads to keratocyte damage; after 6 months a repopulation by proliferating cells, a distribution of CD34-positive keratocytes as in control and an increase in collagen fibre diameter were observed. These modifications are the morphological correlate of the process leading to an increase in biomechanical stability.
    Clinical and Experimental Ophthalmology 01/2010; 38(1):49-56. · 1.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rebuilding brain structure and neural circuitries by transplantation of fetal tissue is a strategy to repair the damaged nervous system and is currently being investigated using striatal primordium in Huntington's disease (HD) patients. Four HD patients underwent bilateral transplantation with human fetal striatal tissues (9-12 week gestation). Small blocks of whole ganglionic eminencies were processed to obtain cell suspension and then stereotactically grafted in the caudate head and in the putamen. Follow-up period ranged between 18 and 34 months (mean, 24.7 months). Surgery was uneventful. Starting from the fourth month after grafting, neo-generation of metabolically active tissue with striatal-like MRI features was observed in 6 out of 8 grafts. The increase in D2 receptor binding suggested striatal differentiation of the neo-generated tissue in 3 patients. New tissue, connecting the developing grafts with the frontal cortex and, in one case, with the ventral striatum, was also observed. The new tissue growth halted after the ninth month post transplantation. All patients showed stabilization or improvement in some neurological indices. No clinical and imaging signs, suggestive of graft uncontrolled growth, were seen. This study provides the first evidence in humans that neuroblasts of a striatal primordium can develop and move into the brain after neurotransplantation. Primordium development resulted in the building of a new structure with the same imaging features as the corresponding mature structure, combined with short- and long-distance targeted migration of neuroblasts. The results of this study support both the reconstructive potential of fetal tissue and the remarkably retained plasticity of adult brain. Further studies are necessary to assess the clinical efficacy of the human fetal striatal transplantation.
    Experimental Neurology 12/2009; 222(1):30-41. · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Phosphodiesterase type 5 (PDE5) inhibitors ameliorate low urinary tract (LUT) symptoms in men with ED and symptomatic benign prostatic hyperplasia (BPH). PDE5 is highly expressed in rat and human bladder, where it regulates cyclic guanosine monophosphate (cGMP) degradation, muscle tone, and proliferation. To investigate PDE5 tissue distribution and activity in human LUT tissues (urethra, prostate, and bladder). PDE5 expression and activity were analyzed and compared within the same BPH patient in LUT tissues and in smooth muscle cells (SMCs) cultured from urethra, prostate, and bladder. In LUT tissues, PDE5 was localized by immunohistochemistry and mRNA expression by quantitative real-time polymerase chain reaction. Proliferation assay was used as readout of PDE5 activity, evaluated as ability of vardenafil to increase the antiproliferative effect of different nitric oxide (NO)/cGMP pathway activators [the PDE5-resistant cGMP analog Sp-8-Br-PET-cGMPS, the NO donor sodium nitroprusside (SNP), and the soluble guanylate cyclase (sGC) stimulator BAY 41-8543]. In all the LUT tissues, PDE5 was immunolocalized in blood vessels and in muscular fibres, but not in epithelium. PDE5 mRNA expression was higher in urethra and bladder than in prostate SMC. The antiproliferative effect of Sp-8-Br-PET-cGMPS was similar in all LUT SMC. In prostatic SMC, SNP and BAY 41-8543 show a dose-dependent antiproliferative effect that resulted marginally enhanced by vardenafil. Conversely, in urethra and bladder SMC the antiproliferative effect of SNP and BAY 41-8543 was lower than in prostatic SMC, but it was significantly enhanced by vardenafil. In urethral and bladder cells vardenafil half-maximal response inhibiting concentration was in the subnanomolar range, whereas in prostate cells it resulted significantly higher. The highest expression and biological activity of PDE5 was found in bladder. However, a consistent PDE5 expression and activity was also found in prostatic urethra. In contrast, the prostate gland showed the lowest PDE5 abundance and cultures derived from this tissue were less sensitive to vardenafil.
    Journal of Sexual Medicine 09/2009; 7(1 Pt 1):59-69. · 3.51 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction.  We have previously demonstrated that oxytocin (OT) and endothelin-1 (ET-1) peripherally regulate epididymal motility in an estrogen-dependent way. Because RhoA/Rho-kinase (ROCK) pathway is a contractile effector downstream to both OT and ET-1 receptors, we hypothesized an estrogenic modulation of OT- and ET-1-induced contraction through the up-regulation of RhoA/ROCK signaling.Aim.  To evaluate the effect of changing endocrine milieu on RhoA/ROCK pathway in the epididymis.Methods.  We induced a pharmacological hypogonadotropic hypogonadism in rabbits and replaced hypogonadal animals with different sex steroids (testosterone, T, or estradiol valerate, [E2v]). Effects of estrogen deprivation were also evaluated in rabbits chronically treated with the P450-aromatase inhibitor letrozole. An “in vitro” model of human epididymal smooth muscle cells was established and stimulated with sex hormones (72 hours). Protein and mRNA expression and functional activity of RhoA/ROCK signaling were studied by quantitative reverse transcriptase-polymerase chain reaction, immunohistochemistry, western blot analysis, cell migration and by “in vitro” contractility studies using the ROCK inhibitor Y-27632.Main Outcome Measures.  Effects of sex steroids on expression and functional activation of RhoA/ROCK signaling in rabbit epididymis and human epididymal smooth muscle cells.Results.  The relaxant effect of Y-27632 on ET-1-pre-contracted epididymal strips was significantly reduced in hypogonadal rabbits, as well as in letrozole-treated animals. T supplementation normalized T plasma levels, but not Y-27632 epididymal strip sensitivity. E2v not only completely restored Y-27632 responsiveness but even amplified it, indicating an estrogenic up-regulation of RhoA/ROCK pathway. Accordingly, ROCK1 protein and gene expressions were strongly induced by E2v but not by T. The estrogen-induced up-regulation of RhoA/ROCK signaling was confirmed in human epididymal smooth muscle cells.Conclusions.  Our results suggest that estrogens regulate epididymal motility by increasing RhoA/ROCK signaling, and therefore calcium sensitivity, which tunes up responsiveness to contractile factors. Fibbi B, Filippi S, Morelli A, Vignozzi L, Silvestrini E, Chavalmane A, De Vita G, Marini M, Gacci M, Manieri C, Vannelli GB, and Maggi M. Estrogens regulate humans and rabbit epididymal contractility through the Rhoa/Rho-kinase pathway. J Sex Med 2009;6:2173–2186.
    Journal of Sexual Medicine 04/2009; 6(8):2173 - 2186. · 3.51 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Most men following radical retropubic prostatectomy (RRP) are afflicted by erectile dysfunction (ED). RRP-related ED occurs as a result of surgically elicited neuropraxia, leading to histological changes in the penis, including collagenization of smooth muscle and endothelial damage. To verify whether hypogonadism could contribute to the pathogenesis of RRP-ED. Effects of testosterone (T), alone or in association with long-term tadalafil (Tad) treatment in a rat model of bilateral cavernous neurotomy (BCN). Penile tissues from rats were harvested for vasoreactivity studies 3 months post-BCN. Penile oxygenation was evaluated by hypoxyprobe immunostaining. Phosphodiesterase type 5 (PDE5), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) mRNA expression were quantified by Real Time quantitative reverse transcription polymerase chain reaction (qRT-PCR). In BCN rats, we observed the onset of an overt condition of hypogonadism, characterized by reduced T plasma level, reduced ventral prostate weight, reduced testis function (including testis weight and number of Leydig cells), with an inadequate compensatory increase of luteinizing hormone. BCN induced massive penile hypoxia, decreased muscle/fiber ratio, nNOS, eNOS, PDE5 expression, increased sensitivity to the nitric oxide donor, sodium nitroprusside (SNP), and reduced the relaxant response to acetylcholine (Ach), as well as unresponsiveness to acute Tad dosing. In BCN rats, chronic Tad-administration normalizes penile oxygenation, smooth muscle loss, PDE5 expression, SNP sensitivity, and the responsiveness to the acute Tad administration. Chronic Tad treatment was ineffective in counteracting the reduction of nNOS and eNOS expression, along with Ach responsiveness. T supplementation, in combination with Tad, reverted some of the aforementioned alterations, restoring smooth muscle content, eNOS expression, as well as the relaxant response of penile strips to Ach, but not nNOS expression. BCN was associated with hypogonadism, probably of central origin. T supplementation in hypogonadal BCN rats ameliorates some aspects of BCN-induced ED, including collagenization of penile smooth muscle and endothelial dysfunction, except surgically induced altered nNOS expression.
    Journal of Sexual Medicine 03/2009; 6(5):1270-83. · 3.51 Impact Factor

Publication Stats

973 Citations
162.85 Total Impact Points

Institutions

  • 2009–2014
    • University of Florence
      • • Dipartimento di Scienze Biomediche, Sperimentali e Cliniche
      • • Dipartimento di Scienze della Salute
      Florens, Tuscany, Italy
  • 2013
    • Italian Cancer League
      Roma, Latium, Italy