Publications (32)105.38 Total impact
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Article: Evidence for Adapted Physical Activity as an Effective Intervention for Upper Limb Mobility and Quality of Life in Breast Cancer Survivors.
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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; -
Article: Cadmium induces alterations in the human spinal cord morphogenesis.
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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 -
Article: Distribution of sugar residues in human placentas from pregnancies complicated by hypertensive disorders.
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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. · 1.23 Impact Factor -
Article: Lectin binding in normal, keratoconus and cross-linked human corneas.
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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. · 1.23 Impact Factor -
Article: Effects of riboflavin/UVA corneal cross-linking on keratocytes and collagen fibres in human cornea.
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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. · 1.98 Impact Factor -
Article: Human striatal neuroblasts develop and build a striatal-like structure into the brain of Huntington's disease patients after transplantation.
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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. · 4.70 Impact Factor -
Article: Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract.
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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. · 3.55 Impact Factor -
Article: Estrogens Regulate Humans and Rabbit Epididymal Contractility Through the RhoA/Rho‐kinase Pathway
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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. · 3.55 Impact Factor -
Article: Cavernous neurotomy in the rat is associated with the onset of an overt condition of hypogonadism.
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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. · 3.55 Impact Factor -
Article: Dihydrotestosterone and leptin regulate gonadotropin-releasing hormone (GnRH) expression and secretion in human GnRH-secreting neuroblasts.
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ABSTRACT: The reversal of hypogonadotropic hypogonadism (HH), occurring after discontinuation of testosterone therapy in adolescents with delayed puberty and in a small percentage of adults with congenital HH, suggests a role for androgens in favoring a spontaneous recovery of reproductive function. We investigated the effect of androgens and leptin on gonadotropin-releasing hormone (GnRH) expression and secretion in human GnRH-secreting neuroblasts (FNC-B4). Quantitative real-time polymerase chain reaction RT-PCR for mRNA expression and radioimmunoassay for GnRH secretion were used. Immunohistochemical studies assessed GnRH protein expression. FNC-B4 migration was analyzed with multiwell Boyden chamber technique. Effects of the non-aromatizable androgen dihydrotestosterone (DHT) and leptin in FNC-B4 were tested after 24 and 48 hours. Exposure to increasing concentrations of DHT after 24 hours significantly stimulated GnRH mRNA in FNC-B4. This effect was still present after prolonged exposure (48 hours). Similarly, treatment with leptin significantly induced GnRH mRNA after 24 hours, but not at 48 hours. Interestingly, mRNA for leptin receptors (LEPR) was significantly reduced after 48 hours of leptin, while, at this time point, it was stimulated by DHT. Coincubation for 48 hours with leptin and DHT maintained the stimulatory effect on both GnRH and LEPR mRNA, suggesting that DHT could stabilize the leptin effect by preventing downregulation of LEPR. Similar results were obtained for GnRH protein expression analysis. Moreover, both DHT and leptin increased GnRH release into the culture medium. We also found that DHT or leptin treatment significantly increased FNC-B4 basal migration. As we previously found that GnRH stimulates FNC-B4 migration, we hypothesized that this effect could be mediated by DHT- and leptin-induced GnRH release. Accordingly, the GnRH antagonist cetrorelix inhibited DHT- and leptin-induced migration. Our results suggest that androgens (adequate hormonal status) could have a positive effect on GnRH neuronal activity by synergizing with leptin (adequate energy status) in the regulatory mechanisms required for reproductive and sexual fitness.Journal of Sexual Medicine 12/2008; 6(2):397-407. · 3.55 Impact Factor -
Article: Cadmium modulates proliferation and differentiation of human neuroblasts.
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ABSTRACT: Cadmium is an environmental pollutant inducing numerous pathological effects, including neurological disorders and brain diseases. However, little is known about the molecular mechanisms of cadmium in affecting neurons and in inducing neurotoxicity in the development of the human brain. We have recently established, cloned, and propagated in vitro a primary long-term cell culture (FNC-B4) obtained from the human fetal olfactory neuroepithelium. In the present study, we show that different concentrations of cadmium chloride (CdCl(2)) induced dose-dependent biological effects in FNC-B4 cells. A low concentration (10 microM) of CdCl(2) stimulated neuroblast growth, whereas a high concentration (100 microM) inhibited the growth and the viability of neuroblasts inducing morphological and cytoskeletal alterations as well as apoptotic cell death. We also observed that CdCl(2) affected, in a dose-dependent manner, the differentiation of FNC-B4 neuroblasts, with increased mRNA and protein levels of differentiation markers and decreased expression levels of neuronal stem markers. Furthermore, differentiated cells co-expressed glial and neuronal markers. We suggest that CdCl(2) in FNC-B4 neuroblasts might represent a selective cue by which, in a heterogeneous primary culture, the more differentiated mature cells die, whereas the undifferentiated cells, at the same time glial and neuronal progenitors, are forced to access a state of differentiation.Journal of Neuroscience Research 10/2008; 87(1):228-37. · 2.74 Impact Factor -
Article: Development of human striatal anlagen after transplantation in a patient with Huntington's disease.
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ABSTRACT: Replacement of damaged neuronal population by fetal tissue transplantation represents a potential treatment for neurodegenerative diseases. Consistent success has been achieved with fetal striatal transplantation in Huntington's disease animal models and patients. We report the neo-generation of metabolically active tissue with striatum-like imaging features after transplantation of striatal primordia in a patient with Huntington's disease. This study represents the first "in vivo" demonstration that a human striatal anlagen, transplanted into the adult human brain, is able to progress in its development and to generate a new anatomical structure in the host, without evidence of neoplasia or teratoma.Experimental Neurology 07/2008; 213(1):241-4. · 4.70 Impact Factor -
Article: Sex steroids and leptin regulate the "first Kiss" (KiSS 1/G-protein-coupled receptor 54 system) in human gonadotropin-releasing-hormone-secreting neuroblasts.
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ABSTRACT: The G-protein-coupled receptor 54 (GPR54) and its ligand kisspeptin, encoded by the KiSS-1 gene, have been involved in the molecular mechanisms underlying the reawakening of gonadotropin-releasing hormone (GnRH) neurons at puberty. GPR54 mutations cause hypogonadotropic hypogonadism in human and mice. Aim. Our aim was to study regulation of the KiSS-1/GPR54 system using a previously characterized primary culture of human fetal GnRH-secreting neuroblasts, FNC-B4. KiSS-1/GPR54 gene and protein expressions in FNC-B4 were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunocytochemistry, and Western blot. Expression of kisspeptin and GPR54 in fetal olfactory mucosa (OM), from which FNC-B4 cells were derived, was analyzed with confocal microscopy. Regulation of KiSS-1/GPR54 expression in FNC-B4 was evaluated in response to sexual steroids and leptin. Effect of kisspeptin on GnRH secretion and migration in FNC-B4 was also investigated. Kisspeptin and GPR54 were immunolocalized and co-expressed with GnRH in OM and FNC-B4 cells. Kisspeptin (1 microM, 24 hours) induced GnRH secretion, but not gene expression, and inhibited migration (IC(50) = 6.28 +/- 3.71 nM) in FNC-B4. The 24-hour exposure to increasing concentrations of 17-beta-estradiol (0.01-1 nM) significantly and dose-dependently decreased, whereas androgens (dihydrotestosterone [DHT], 0.01-1 nM) significantly stimulated KiSS-1/GPR54 mRNA. Testosterone (1 nM) showed a stimulatory effect only after blocking its aromatization with letrozole. In addition, leptin (1 nM, 24 hours), an adipocyte-derived hormone acting on the reproductive axis, significantly increased KiSS-1/GPR54 expression in FNC-B4. Immunocytochemistry and Western blot analysis confirmed the regulatory effects found with qRT-PCR. Interestingly, leptin (1 nM, 24 hours) also significantly increased both leptin receptor (LEPR) and androgen receptor (AR) mRNA. DHT (0.01-1 nM) also up-regulated LEPR and AR genes, suggesting a synergistic action between leptin and androgens aimed to up-regulate the KiSS-1/GPR54 system, which, in contrast, was inhibited by estrogens. Our results indicate that an interplay between metabolic and sexual hormones may trigger the KiSS-1/GPR54 signaling to GnRH neurons suggesting new mechanisms which regulate puberty onset.Journal of Sexual Medicine 06/2008; 5(5):1097-113. · 3.55 Impact Factor -
Article: The sialoglycoconjugates in the oviducts of fertile and postmenopausal women.
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ABSTRACT: The aim of the study was to investigate the distribution of the sialoderivatives of the glycoconjugates in the oviduct of normally menstruating and postmenopausal women. Biopsies of ampullary and isthmic portions of the oviduct were obtained from fertile women, in proliferative and secretive phases, and from postmenopausal subjects. The study was carried out using digoxigenin-labelled lectins (MAA, SNA and PNA) in addition to the use of enzymatic and chemical treatments to characterize the different glycosidic linkages of the sialoderivatives and to obtain information on their structure. No appreciable difference in sialoderivatives distribution was observed among the oviducts, particularly at the epithelium luminal surface, of the fertile women in the two menstrual cycle phases or among those of the fertile and some postmenopausal women, independently from age. Moreover, no appreciable difference of distribution was observed between the ampullary and the isthmic portions in both the study groups. In the fertile women sialoderivatives present at the luminal surface of the epithelial cells could play a role in sperm capacitation and mobility, and facilitate the transit of the egg and of the early embryo along the oviducts. The similar distribution of sialoderivatives in the oviduct epithelium of some postmenopausal women of different age, compared to the fertile ones, suggests a maintaining of some functions of the organ, independently from the age of the woman. This could be due, in some cases, to the influence of remaining still sufficient sex hormonal levels.Maturitas 12/2007; 58(3):269-84. · 2.77 Impact Factor -
Article: Distribution of the glycoconjugate oligosaccharides in the human placenta from pregnancies complicated by altered glycemia: lectin histochemistry.
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ABSTRACT: The aim of this study was to investigate the distribution of the oligosaccharides of the glycoconjugates in placentas from pregnancies complicated by different degree of altered glycaemia. Placentas from women with physiological pregnancies (group 1), with pregnancies complicated by minor degree of glucose intolerance (group 2) and with pregnancies complicated by gestational diabetes mellitus (GDM) treated with insulin (group 3) were collected. Ten lectins were used (ConA, WGA, PNA, SBA, DBA, LTA, UEA I, GSL II, MAL II and SNA) in combination with chemical and enzymatic treatments. The data showed a decrease of sialic acid linked alpha(2-6) to galactose/N-acetyl-D-galactosamine and an increase of N-acetyl-D-glucosamine in the placentas of the pathological groups, in particular the group 3, comparing to the group 1. A decrease of L-fucose (LTA) and D-galactose-(beta1-3)-N-acetyl-D-galactosamine, and an increase and/or appearance of L-fucose (UEA I) and N-acetyl-D-galactosamine were observed in both the pathological groups, particularly in the group 2, with respect to the group 1. In GDM, and even in pregnancies with a simple alteration of maternal glycaemia, the changes in the distribution of oligosaccharides could be related to alteration of the structure and functionality of the placenta.Histochemie 10/2007; 128(3):263-73. · 2.59 Impact Factor -
Article: Characterization and functional role of androgen-dependent PDE5 activity in the bladder.
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ABSTRACT: Benign prostate hyperplasia is the most common disease in the aging male, often comorbid with erectile dysfunction. Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, and vardenafil) decrease lower urinary tract symptoms in patients with erectile dysfunction and BPH. We studied PDE5 expression and activity in the human bladder and PDE5i effects both in vitro (human and rat) and in vivo (rat). PDE5 is highly expressed in rat and human bladder and immunolocalized in vascular endothelium and muscle fibers. Sildenafil, tadalafil, and vardenafil blocked 70% of the total cGMP-catabolizing activity; vardenafil was the most potent (IC(50) = 0.3 nm). In human bladder cells and in rat strips, a PDE-resistant cGMP analog, SP-8-Br-PET-cGMPS, induced, respectively, a consistent antiproliferative and relaxant effect. In contrast, the nitric oxide donor sodium nitroprusside (SNP) was almost ineffective. However, blocking PDE5 with vardenafil increased SNP antiproliferative and relaxant activity up to the level observed with SP-8-Br-PET-cGMPS. We also found that castration decreased, and T supplementation restored, PDE5 gene expression in rat bladder. Accordingly, bladder strips from castrated rats were more sensitive to SNP-induced relaxation than strips from control or T-replaced rats, whereas in the presence of vardenafil, all groups showed the same SNP sensitivity. To discover whether vardenafil affects bladder activity in vivo, the rat bladder outlet obstruction model was used. Chronic treatment with 10 mg/kg.d vardenafil significantly reduced nonvoiding contractions (47%, P < 0.05 vs. placebo) up to tamsulosin level (51%). Overall, these results demonstrate that PDE5 regulates bladder smooth muscle tone, strongly limiting the nitric oxide/cGMP signaling, and that vardenafil, by blocking PDE5, may be a possible therapeutic option for bladder dysfunction by ameliorating irritative lower urinary tract symptoms.Endocrinology 03/2007; 148(3):1019-29. · 4.46 Impact Factor -
Article: Lectin binding in the umbilical cord in altered glycemia.
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ABSTRACT: Content and distribution of the oligosaccharides in the umbilical cord from pregnancies with altered glycemia were investigated. A prospective cohort study was conducted in the Florence Policlinic of Careggi, Italy. Samples of cord from physiological pregnancies (n=20), from pregnancies with minor degree of glucose intolerance (n=20) and from pregnancies with gestational diabetes mellitus (GDM) treated with insulin (n=20) were collected. Eleven lectins were used (ConA, WGA, PNA, SBA, DBA, LTA, UEA I, OOA, GSL II, MAL II and SNA) in combination with chemical and enzymatic treatments. Increase of N-acetyl-d-glucosamine and a loss of sialic acid in the umbilical cord of the cases with minor degree of glucose intolerance with respect to the other study groups was observed. d-Galactose(beta1-->3)-N-acetyl-d-galactosamine, N-acetyl-d-galactosamine and l-fucose were in less amount in both the pathological groups with respect to the control one. The increase of some glycoconjugates carbohydrates and the loss of others in the umbilical cord from pregnancies with minor degree of glucose intolerance might be related to its morphofunctional alterations in a not diabetic altered glycemia. Moreover, the treatment with insulin in the GDM might play a role in restoring partially the normal glycosilation in the cord components in the attempt to renew some their functions.European Journal of Obstetrics & Gynecology and Reproductive Biology 01/2007; 130(1):30-41. · 1.97 Impact Factor -
Article: Ultrasound thermal damage to rabbit corneas after simulated phacoemulsification.
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ABSTRACT: To determine rabbit cornea thermal tolerance and evaluate the effects of ultrasound (US) on this tissue after applying defined US heat doses. Eye Clinic; Anatomy Histology and Forensic Medicine, University of Florence, Florence, Italy. Hyperthermia was induced in rabbit corneas using US, simulating a phacoemulsification procedure. The US power was set at 100% in continuous mode, and temperature values were reached within 10 seconds of the onset of US treatment. Corneal surface temperatures were continuously monitored and recorded by thermographic registration. The eyes of 16 rabbits were examined: 4 controls, 8 treated at 40 degrees C for 10 seconds, 8 treated at 50 degrees C for 10 seconds, and 12 treated at 60 degrees C for 10 seconds. All 32 corneal buttons were removed and prepared for light microscopic evaluation with hematoxylin and eosin staining, trichromic staining, and zinc iodide-osmium tetroxide solution. The 12 corneas treated at 60 degrees C for 10 seconds were also processed for immunohistochemical analysis. Corneas at 40 degrees C for 10 seconds were grossly and histologically normal and were not different from control corneas. Corneas at 50 degrees C for 10 seconds showed initial stromal damage with collagen disorganization, mild stromal edema, and initial signs of keratocyte damage. Half of the corneas at 60 degrees C for 10 seconds were examined at time 0 and the other half after 1 week. At time 0, massive corneal damage with epithelial cell edema, collagen disorganization, severe stromal edema, intrastromal vacuole formation, plump keratocyte nuclei, and endothelial cell detachment were found, as was a severely impaired nerve plexus. At 1-week follow-up, corneas showed persistent stromal and endothelial cell edema with an increase activated keratocytes and mitotic features in the stroma and the epithelial layer. Rabbit corneas showed a considerable tolerance to US damage up to 50 degrees C. Higher thermal doses produced severe histological damage, even though corneas showed a considerable plasticity due to their regenerative capacity.Journal of Cataract [?] Refractive Surgery 12/2005; 31(11):2180-6. · 2.26 Impact Factor -
Article: Role of endothelin-1 in the migration of human olfactory gonadotropin-releasing hormone-secreting neuroblasts.
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ABSTRACT: FNC-B4 neuroblasts that express both neuronal and olfactory markers have been established and cloned. These cells express GnRH and both the endothelin-1 (ET-1) gene and protein and respond in a migratory manner to GnRH in a dose-dependent manner. Previous research has shown that FNC-B4 cells produce and respond to ET-1 by regulating the secretion of GnRH through endothelin type A receptors and by stimulating their proliferation through endothelin type B (ETB) receptors. In this study, we found that FNC-B4 cells are able to migrate in response to ET-1 through the involvement of ETB receptors. Combined immunohistochemical and biochemical analyses showed that ET-1 triggered actin cytoskeletal remodeling and a dose-dependent increase in migration (up to 6-fold). Whereas the ETB receptor antagonist (B-BQ788) blunted the ET-1-induced effects, the ETA receptor antagonist (A-BQ123) did not. Moreover, we observed that FNC-B4 cells were independently and selectively stimulated by ET-1 and GnRH. We suggest that ET-1, through ETB receptor activation, may be required to maintain an adequate proliferative stem cell pool in the developing olfactory epithelium and the subsequent commitment to GnRH neuronal migratory pattern. The coordinate interaction between ET receptors and GnRH receptor participates in the fully expressed GnRH-secreting neuron phenotype.Endocrinology 11/2005; 146(10):4321-30. · 4.46 Impact Factor -
Article: Oxytocin mediates the estrogen-dependent contractile activity of endothelin-1 in human and rabbit epididymis.
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ABSTRACT: Epididymis is a sex steroid (androgen + estrogen)-sensitive duct provided with spontaneous motility, allowing sperm transport. We previously reported that the oxytocin (OT) receptor (OTR) mediates an estrogen-dependent increase in epididymal contractility. Because endothelin (ET)-1 also regulates epididymal motility, we tested its sex steroid dependence in a rabbit model. We demonstrated that estrogens up-regulate responsiveness to ET-1, which is reduced by blocking aromatase activity (letrozole, 2.5 mg/kg) or by triptorelin (2.9 mg/kg)-induced hypogonadism, whereas it is fully restored by estradiol valerate (3.3 mg/kg weekly) but not by testosterone enanthate (30 mg/kg weekly). However, changing sex steroid milieu did not affect either ET-1, its receptor gene, or protein expression. Two structurally distinct OTR-antagonists [(d(CH2)5(1), Tyr(Me)(2), Orn(8))-OT and atosiban] almost completely abolished ET-1 contractility, without competing for [125I]ET-1 binding, suggesting that OT/OTR partially mediates ET-1 action. Immunohistochemical studies in human and rabbit epididymis demonstrated that both OT and its synthesis-associated protein, neurophysin I, are expressed in the epithelial cells facing the muscular layer, suggesting local OT production. Quantitative RT-PCR demonstrated a high abundance of OT transcripts in human epididymis. OT transcript was also originally detected and partially sequenced in rabbit epididymis. To verify whether ET-1 regulates OT release, we used rabbit epididymal epithelial cell cultures. These cells expressed a high density of [125I]ET-1 binding sites and responded to ET-1 with a dose-dependent OT release. Hence, we propose that an ET-1-induced OT/OTR system activation underlies the estrogen-dependent hyperresponsiveness to ET-1. These local sources might promote the spontaneous motility necessary for sperm transport.Endocrinology 09/2005; 146(8):3506-17. · 4.46 Impact Factor
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2004–2011
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Università degli Studi di Firenze
- • Dipartimento di Scienze della Salute
- • Dipartimento di Scienze Biomediche, Sperimentali e Cliniche
- • Dipartimento di Medicina Sperimentale e Clinica
Florence, Tuscany, Italy
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