giovanna danza | Università degli Studi di Firenze (University of Florence) (original) (raw)
Papers by giovanna danza
Prostate carcinoma is among the most common causes of cancer-related death in men, representing 1... more Prostate carcinoma is among the most common causes of cancer-related death in men, representing 15% of all male malignancies in developed countries. Neuroendocrine differentiation (NED) has been associated with tumor progression, poor prognosis, and with the androgen-independent status. Currently, no successful therapy exists for advanced, castration-resistant disease. Because hypoxia has been linked to prostate cancer progression and unfavorable outcome, we sought to determine whether hypoxia would impact the degree of neuroendocrine differentiation of prostate cancer cells in vitro.Results: Exposure of LNCaP cells to low oxygen tension induced a neuroendocrine phenotype, associated with an increased expression of the transcription factor neurogenin3 and neuroendocrine markers, such as neuron-specific enolase, chromogranin A, and β3-tubulin. Moreover, hypoxia triggered a significant decrease of Notch 1 and Notch 2 mRNA and protein expression, with subsequent downregulation of Notch...
European Journal of Pharmaceutical Sciences, 1994
World Journal of Gastroenterology
to ( malian s d callus. W e, t ere obtained w inant L uced d d r e first time a 1 nse t d existen... more to ( malian s d callus. W e, t ere obtained w inant L uced d d r e first time a 1 nse t d existence o d plant s ©
The Journal of Clinical Endocrinology & Metabolism, 2020
Purpose Exogenous gonadotrophins administration during in vitro fertilization/intracytoplasmic sp... more Purpose Exogenous gonadotrophins administration during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles could significantly alter the endogenous follicular regulation system and could influence oocyte quality. The analysis of the follicular fluid (FF) cytokine and hormone profiles in physiological natural cycles is crucial to appreciate the role of FF milieu on follicle development. So far, the FF cytokine profile has been analyzed only in controlled ovarian stimulation cycles and in modified natural cycles. Our study defines, in physiological natural cycles, the cytokine and hormone profiles of individual FF aspirated from antral follicles. Methods A total of 203 FFs obtained from 83 women with regular menstrual cycles undergoing ovarian tissue cryopreservation were analyzed: 115 FFs from Group 1 (10 to 29 years of age) and 88 FFs from Group 2 (30 to 40 years of age). In individual FF, 27 cytokines were measured with xMAP technology, and progesterone, estro...
Andrology, 2020
This article is protected by copyright. All rights reserved Background.Infertility affects 7-12% ... more This article is protected by copyright. All rights reserved Background.Infertility affects 7-12% of men and its etiology is unknown in half of cases. To fill this gap, use of the male genital tract colour-Doppler ultrasound (MGT-CDUS) has progressively expanded. However, MGT-CDUS still suffers from lack of standardization. Hence, the European Academy of Andrology(EAA) has promoted a multicenter study ("EAA ultrasound study") to assess MGT-CDUS characteristics of healthy-fertile men to obtain normative parameters. Objectives.To report (a)the development and methodology of the "EAA ultrasound study", (b)the clinical characteristics of the cohort of healthy-fertile men and (c)the correlations of both fertility history and seminal features with clinical parameters. Methods.A cohort of 248 healthy-fertile men (35.3±5.9 years) was studied. All subjects were asked to undergo, within the same day, clinical, biochemical, seminal evaluation and MGT-CDUS before and after ejaculation. Results.The clinical, seminal and biochemical characteritics of the cohort have been reported here. The seminal characteristics were consistent with those reported by the WHO (2010) for the 50 th and 5 th centile for fertile men. Normozoospermia was observed in 79.6% of men, while normal sperm vitality was present in almost the entire sample. Time to pregnancy(TTP) was 3.0[1.0-6.0] months. TTP was negatively correlated with sperm vitality (Adj.r=-0.310,p=0.011), but not with other seminal, clinical or biochemical parameters. Sperm vitality and normal morphology were positively associated with fT3 and fT4 levels, respectively (Adj.r=0.244,p<0.05 and Adj.r=0.232,p=0.002). Sperm concetration and total count were negatively associated with FSH levels and positively, along with progressive motility, with mean testis volume (TV). Mean TV was 20.4±4.0 ml and the lower reference values for right and left testes were 15.0 and 14.0 ml. Mean TV was negatively associated with gonadotrophins levels and pulse pressure. Varicocele was found in 33% of men. Conclusions.The cohort studied confirms the WHO data for all semen parameters and represents a reference with which to assess MGT-CDUS normative parameters.
Journal of Mass Spectrometry, 2018
Monoterpene-glycosides are important aroma precursors which, undergo hydrolysis, confer intense f... more Monoterpene-glycosides are important aroma precursors which, undergo hydrolysis, confer intense floral notes to the wines. Therefore, the knowledge of the nature of the sugar residues and the structure of these molecules is of great interest. In present study, liquid chromatography (LC) separation coupled with different mass spectrometry (MS) experiments for the characterization of these compounds were explored. The LC parameters were tuned to optimize the resolution between the analytes present in grape sample extracts. Twenty principal peaks with a relative abundance >1% were selected and divided in four classes characterized by different molecular weight. In general, positive ionization of the studied compounds shown the [M+NH4] + ion as base peak. On the contrary, a distribution between [M+Cl]and [M+HCOO]species was observed in negative ion mode. However, a clear differentiation between the studied compounds was only possible by combining both LC and tandem mass spectrometry (MS/MS). Indeed, by applying a series of energy resolved MS/MS experiments (ERMS) and monitoring both positive and negative ions, a structural characterization of the analytes was achieved. The proposed LC-MS/MS approach provided the profile of monoterpenol-diglycosides and allowed the identification of a series of isobaric terpene-diglycosides in grape. The study of their MS/MS spectra evidenced the structure of geranic and/or nerolic acid aglycones. In order to verify the interest of studied compounds, a preliminary evaluation of the intensity of signals of these glycosides were carried out. The obtained results showed a significantly difference between the grape samples collected in two different vintages.
American Journal of Physiology-Endocrinology and Metabolism, 1993
Cultured Sertoli cells of 20-day-old rats were found to produce and release endothelin-1-like imm... more Cultured Sertoli cells of 20-day-old rats were found to produce and release endothelin-1-like immunoreactivity (ET-1-LI) under follicle-stimulating hormone control. The elution profile of ET-1-LI from extracts of spent Sertoli cell culture medium corresponds to that of synthetic ET-1, suggesting a testicular production of authentic ET-1. In contrast, the conditioned medium from rat Leydig cells did not contain ET-1-LI. Immunohistochemical studies confirmed that, in 20-day-old rats, the positive staining was confined to some Sertoli cells, whereas interstitial cells were negative. In the adult rat testis the positivity was not limited to the tubular compartment (Sertoli cells) but was also present in the interstitium. A high concentration (13 pmol/mg protein) of high-affinity (dissociation constant = 0.6 nM) 125I-labeled ET-1 binding sites was present in Leydig cells. These sites bind ET-1 and ET-2 with 1,000-fold higher affinity than ET-3, suggesting that they correspond to the subt...
L'Endocrinologo, 2010
Il dosaggio delle metanefrine nella diagnosi del feocromocitoma: vantaggi clinici e problematiche... more Il dosaggio delle metanefrine nella diagnosi del feocromocitoma: vantaggi clinici e problematiche di laboratorio L a diagnosi di feocromocitoma si basa sui risultati di laboratorio. Benché il quadro clinico dipenda dall'azione delle catecolamine liberate dal tumore, il marker diagnostico più sensibile risiede nel dosaggio delle metanefrine. Questi metaboliti delle catecolamine si formano infatti all'interno del tessuto tumorale in modo continuo e vengono rilasciati in maniera costante, a differenza delle catecolamine, la cui liberazione è episodica. È per tale motivo che il dosaggio delle metanefrine comporta una bassissima incidenza di falsi negativi ed è il test da richiedere nel sospetto di feocromocitoma. Le metanefrine (metanefrina e normetanefrina) possono essere misurate nel plasma o nelle urine delle 24 ore. Il dosaggio plasmatico si accompagna alla facilità di raccolta del campione e a una maggior specificità, ma risulta più problematico per i bassi livelli di metanefrine circolanti. Il dosaggio nelle urine, dove le concentrazioni sono maggiori, risulta più facile, ma è meno specifico per possibili interferenze alimentari e comporta il problema della corretta raccolta del campione. A tutt'oggi esistono metodi di dosaggio immunologici, metodi in high performance liquid chromatography (HPLC) con detector elettrochimico o fluorimetrico e in spettrometria di massa tandem (LC-MS/MS). I primi, di più facile esecuzione, non sembrano offrire sufficiente accuratezza. Le misure in HPLC offrono risultati analitici migliori. La LC-MS/MS costituisce il gold standard e si avvia ad essere la misura di riferimento nel prossimo futuro.
L'Endocrinologo, 2000
L' enzima steroidi 5α-riduttasi, che comprende due isoenzimi denominati tipo 1 e tipo 2, ha un ru... more L' enzima steroidi 5α-riduttasi, che comprende due isoenzimi denominati tipo 1 e tipo 2, ha un ruolo fondamentale nel metabolismo degli androgeni poiché catalizza la conversione del testosterone in diidrotestosterone (DHT). Il DHT è l'androgeno più potente dell'organismo e svolge un ruolo fisiologico fondamentale nella differenziazione sessuale e nello sviluppo dei
L'Endocrinologo, 2003
L' irsutismo si definisce come la presenza, nella donna, di peli eccessivi in zone corporee e con... more L' irsutismo si definisce come la presenza, nella donna, di peli eccessivi in zone corporee e con caratteristiche tipiche dell'uomo (peli terminali in aree sessuali). Insieme all'acne e all'alopecia, è la manifestazione di una aumentata produzione o alterata funzionalità degli androgeni. A parità di livelli androgenici, la severità dei sintomi è molto diversa da paziente a paziente e alcune
American Journal of Physiology-Endocrinology and Metabolism, 2019
Metabolic syndrome (MetS) clusters cardiovascular and metabolic risk factors along with hypogonad... more Metabolic syndrome (MetS) clusters cardiovascular and metabolic risk factors along with hypogonadism and erectile dysfunction. Lifestyle modifications including physical exercise (PhyEx) are well-known treatments for this condition. In this study, we analyzed the effect of PhyEx on hypothalamic-pituitary-testis axis and erectile function by use of an animal MetS model, previously established in rabbits fed a high-fat diet (HFD). Rabbits fed a regular diet (RD) were used as controls. A subset of both groups was trained on a treadmill. HFD rabbits showed typical MetS features, including HG (reduced T and LH) and impairment of erectile function. PhyEx in HFD rabbits completely restored plasma T and LH and the penile alterations. At testicular and hypothalamic levels, an HFD-induced inflammatory status was accompanied by reduced T synthesis and gonadotropin-releasing hormone (GnRH) immunopositivity, respectively. In the testis, PhyEx normalized HFD-related macrophage infiltration and in...
![Research paper thumbnail of Synthesis of 5,6,6-[2H3]finasteride and quantitative determination of finasteride in human plasma at picogram level by an isotope-dilution mass spectrometric method](https://attachments.academia-assets.com/91962154/thumbnails/1.jpg)
](Journal of Chromatography B: Biomedical Sciences and Applications, 1995
Finasteride is a potent inhibitor of the enzyme steroid 5a-reductase now approved as a drug for t... more Finasteride is a potent inhibitor of the enzyme steroid 5a-reductase now approved as a drug for the treatment of benign prostatic hyperplasia. We describe an original method for the quantitative determination of finasteride at picogram level in human plasma by isotope-dilution gas chromatography mass spectrometry. 5,6,6-[2H3]Finasteride was synthesized with an high ratio of trideuteration (finasteride/[2H3]finasteride = 0.007) allowing its optimal use as internal standard. Plasma samples were purified in a single-step procedure on solid-phase extraction C~8 columns with a recovery />90%. Samples were injected in the GC-MS instrument without any derivatization and the minimum detection level of finasteride was 50 pg with a signal-to-noise ratio of 6:1. The coefficients of variation for the 5 and 10 ng/ml (plasma) concentrations were 5.8% and 4%, respectively. The method has been applied to the determination of the plasma pharmacokinetic of finasteride in five male volunteers treated with a single 5-mg dose of the drug, affording kinetic parameters which are in good agreement with the values previously reported with a different methodology. The present method results accurate, specific, sensible and reliable for a routinely determination of finasteride at picogram levels.
The Endocrine Society's 93rd Annual Meeting & Expo, June 4–7, 2011 - Boston, 2011
Diagnostic Pathology, 2016
Background: Carbonic anhydrase IX is a member of α-carbonic anhydrases that is preferentially exp... more Background: Carbonic anhydrase IX is a member of α-carbonic anhydrases that is preferentially expressed in solid tumors. It enables bicarbonate transport across the plasma membrane, neutralizing intracellular pH and conferring to cancer cells a survival advantage in hypoxic/acidic microenvironments. Overexpression of carbonic anhydrase IX in cancer tissues is regulated by hypoxia inducible factor 1α − mediated transcription and the enzyme is considered a marker of tumor hypoxia and poor outcome. The role of carbonic anhydrase IX in prostate cancer has not been fully clarified and controversy has arisen on whether this enzyme is overexpressed in hypoxic prostate cancer tissues. Methods: We analyzed the expression of carbonic anhydrase IX and hypoxia inducible factor 1α in two prostate cancer cell lines, LNCaP and PC-3, and in 110 cancer biopsies, by western blotting and immunocyto/histochemistry. Results: In LNCaP and PC-3 cells, carbonic anhydrase IX was mostly cytoplasmic/nuclear, with very limited membrane localization. Nuclear staining became stronger under hypoxia. When we analyzed carbonic anhydrase IX expression in human prostate cancer biopsies, we found that protein staining positively correlated with hypoxia inducible factor 1α and with Gleason pattern and score, as well as with the novel grading system proposed by the International Society of Urological Pathology for prostate cancer. Once more, carbonic anhydrase IX was mainly cytoplasmic in low grade carcinomas, whereas in high grade tumors was strongly expressed in the nucleus of the neoplastic cell. An association between carbonic anhydrase IX expression level and the main clinic-pathological features involved in prostate cancer aggressiveness was identified. Conclusions: There was a statistically significant association between carbonic anhydrase IX and hypoxia inducible factor 1α in prostate cancer tissues, that identifies the enzyme as a reliable marker of tumor hypoxia. In addition, carbonic anhydrase IX expression positively correlated with prostate cancer grading and staging, and with outcome, suggesting that the protein may be an independent prognosticator for the disease. The nuclear translocation of the enzyme in hypoxic cancer cells may epitomize a biological switch of the tumor towards a less favorable phenotype.
J Steroid Biochem Mol Biol, 2004
![Research paper thumbnail of Rearrangement of isoxazoline-5-spiro derivatives. Part 3. Indolizine, quinolizine and pyrido[1,2-a]azepine derivatives by sequential rearrangement-annulation](https://attachments.academia-assets.com/91962107/thumbnails/1.jpg)
](Journal of the Chemical Society, Perkin Transactions 1, 1989
Journal of Endocrinological Investigation, 2001
The inhibitors of 5α-reductase isoenzymes (1 and 2) can be schematically divided in three groups ... more The inhibitors of 5α-reductase isoenzymes (1 and 2) can be schematically divided in three groups according they substrate specificity: a) pure or preferential inhibitor of 5α-reductase 1; b) pure or preferential inhibitor of 5α-reductase 2; c) dual inhibitors. Despite the fact that several steroidal and non-steroidal inhibitors have been synthesized and experimented in pharmacological models, only finasteride has been extensively used for clinical purposes. The largest application of finasteride in man has been human benign prostative hyperplasia (BPH). In addition, finasteride has been recently used for treatment of male baldness with a 50% of objective response. In women, finasteride has been used in some control trials for treatment of hirsutism with an objective favorable response. In conclusion, finasteride appears be useful for BPH, baldness and hirsutism (with caution) treatment. On the basis of experimental observations on distribution of 1 and 2 isoenzymes in human skin, scalp and prostate, the dual inhibitors should be more indicated for treatment of BPH and baldness. Similarly, the dual inhibitors seem indicated in attempting to prevent prostatic cancer. The pure 5α-reductase 1 inhibitors seem the ideal drugs for treatment of acne and hirsutism.
Prostate carcinoma is among the most common causes of cancer-related death in men, representing 1... more Prostate carcinoma is among the most common causes of cancer-related death in men, representing 15% of all male malignancies in developed countries. Neuroendocrine differentiation (NED) has been associated with tumor progression, poor prognosis, and with the androgen-independent status. Currently, no successful therapy exists for advanced, castration-resistant disease. Because hypoxia has been linked to prostate cancer progression and unfavorable outcome, we sought to determine whether hypoxia would impact the degree of neuroendocrine differentiation of prostate cancer cells in vitro.Results: Exposure of LNCaP cells to low oxygen tension induced a neuroendocrine phenotype, associated with an increased expression of the transcription factor neurogenin3 and neuroendocrine markers, such as neuron-specific enolase, chromogranin A, and β3-tubulin. Moreover, hypoxia triggered a significant decrease of Notch 1 and Notch 2 mRNA and protein expression, with subsequent downregulation of Notch...
European Journal of Pharmaceutical Sciences, 1994
World Journal of Gastroenterology
to ( malian s d callus. W e, t ere obtained w inant L uced d d r e first time a 1 nse t d existen... more to ( malian s d callus. W e, t ere obtained w inant L uced d d r e first time a 1 nse t d existence o d plant s ©
The Journal of Clinical Endocrinology & Metabolism, 2020
Purpose Exogenous gonadotrophins administration during in vitro fertilization/intracytoplasmic sp... more Purpose Exogenous gonadotrophins administration during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles could significantly alter the endogenous follicular regulation system and could influence oocyte quality. The analysis of the follicular fluid (FF) cytokine and hormone profiles in physiological natural cycles is crucial to appreciate the role of FF milieu on follicle development. So far, the FF cytokine profile has been analyzed only in controlled ovarian stimulation cycles and in modified natural cycles. Our study defines, in physiological natural cycles, the cytokine and hormone profiles of individual FF aspirated from antral follicles. Methods A total of 203 FFs obtained from 83 women with regular menstrual cycles undergoing ovarian tissue cryopreservation were analyzed: 115 FFs from Group 1 (10 to 29 years of age) and 88 FFs from Group 2 (30 to 40 years of age). In individual FF, 27 cytokines were measured with xMAP technology, and progesterone, estro...
Andrology, 2020
This article is protected by copyright. All rights reserved Background.Infertility affects 7-12% ... more This article is protected by copyright. All rights reserved Background.Infertility affects 7-12% of men and its etiology is unknown in half of cases. To fill this gap, use of the male genital tract colour-Doppler ultrasound (MGT-CDUS) has progressively expanded. However, MGT-CDUS still suffers from lack of standardization. Hence, the European Academy of Andrology(EAA) has promoted a multicenter study ("EAA ultrasound study") to assess MGT-CDUS characteristics of healthy-fertile men to obtain normative parameters. Objectives.To report (a)the development and methodology of the "EAA ultrasound study", (b)the clinical characteristics of the cohort of healthy-fertile men and (c)the correlations of both fertility history and seminal features with clinical parameters. Methods.A cohort of 248 healthy-fertile men (35.3±5.9 years) was studied. All subjects were asked to undergo, within the same day, clinical, biochemical, seminal evaluation and MGT-CDUS before and after ejaculation. Results.The clinical, seminal and biochemical characteritics of the cohort have been reported here. The seminal characteristics were consistent with those reported by the WHO (2010) for the 50 th and 5 th centile for fertile men. Normozoospermia was observed in 79.6% of men, while normal sperm vitality was present in almost the entire sample. Time to pregnancy(TTP) was 3.0[1.0-6.0] months. TTP was negatively correlated with sperm vitality (Adj.r=-0.310,p=0.011), but not with other seminal, clinical or biochemical parameters. Sperm vitality and normal morphology were positively associated with fT3 and fT4 levels, respectively (Adj.r=0.244,p<0.05 and Adj.r=0.232,p=0.002). Sperm concetration and total count were negatively associated with FSH levels and positively, along with progressive motility, with mean testis volume (TV). Mean TV was 20.4±4.0 ml and the lower reference values for right and left testes were 15.0 and 14.0 ml. Mean TV was negatively associated with gonadotrophins levels and pulse pressure. Varicocele was found in 33% of men. Conclusions.The cohort studied confirms the WHO data for all semen parameters and represents a reference with which to assess MGT-CDUS normative parameters.
Journal of Mass Spectrometry, 2018
Monoterpene-glycosides are important aroma precursors which, undergo hydrolysis, confer intense f... more Monoterpene-glycosides are important aroma precursors which, undergo hydrolysis, confer intense floral notes to the wines. Therefore, the knowledge of the nature of the sugar residues and the structure of these molecules is of great interest. In present study, liquid chromatography (LC) separation coupled with different mass spectrometry (MS) experiments for the characterization of these compounds were explored. The LC parameters were tuned to optimize the resolution between the analytes present in grape sample extracts. Twenty principal peaks with a relative abundance >1% were selected and divided in four classes characterized by different molecular weight. In general, positive ionization of the studied compounds shown the [M+NH4] + ion as base peak. On the contrary, a distribution between [M+Cl]and [M+HCOO]species was observed in negative ion mode. However, a clear differentiation between the studied compounds was only possible by combining both LC and tandem mass spectrometry (MS/MS). Indeed, by applying a series of energy resolved MS/MS experiments (ERMS) and monitoring both positive and negative ions, a structural characterization of the analytes was achieved. The proposed LC-MS/MS approach provided the profile of monoterpenol-diglycosides and allowed the identification of a series of isobaric terpene-diglycosides in grape. The study of their MS/MS spectra evidenced the structure of geranic and/or nerolic acid aglycones. In order to verify the interest of studied compounds, a preliminary evaluation of the intensity of signals of these glycosides were carried out. The obtained results showed a significantly difference between the grape samples collected in two different vintages.
American Journal of Physiology-Endocrinology and Metabolism, 1993
Cultured Sertoli cells of 20-day-old rats were found to produce and release endothelin-1-like imm... more Cultured Sertoli cells of 20-day-old rats were found to produce and release endothelin-1-like immunoreactivity (ET-1-LI) under follicle-stimulating hormone control. The elution profile of ET-1-LI from extracts of spent Sertoli cell culture medium corresponds to that of synthetic ET-1, suggesting a testicular production of authentic ET-1. In contrast, the conditioned medium from rat Leydig cells did not contain ET-1-LI. Immunohistochemical studies confirmed that, in 20-day-old rats, the positive staining was confined to some Sertoli cells, whereas interstitial cells were negative. In the adult rat testis the positivity was not limited to the tubular compartment (Sertoli cells) but was also present in the interstitium. A high concentration (13 pmol/mg protein) of high-affinity (dissociation constant = 0.6 nM) 125I-labeled ET-1 binding sites was present in Leydig cells. These sites bind ET-1 and ET-2 with 1,000-fold higher affinity than ET-3, suggesting that they correspond to the subt...
L'Endocrinologo, 2010
Il dosaggio delle metanefrine nella diagnosi del feocromocitoma: vantaggi clinici e problematiche... more Il dosaggio delle metanefrine nella diagnosi del feocromocitoma: vantaggi clinici e problematiche di laboratorio L a diagnosi di feocromocitoma si basa sui risultati di laboratorio. Benché il quadro clinico dipenda dall'azione delle catecolamine liberate dal tumore, il marker diagnostico più sensibile risiede nel dosaggio delle metanefrine. Questi metaboliti delle catecolamine si formano infatti all'interno del tessuto tumorale in modo continuo e vengono rilasciati in maniera costante, a differenza delle catecolamine, la cui liberazione è episodica. È per tale motivo che il dosaggio delle metanefrine comporta una bassissima incidenza di falsi negativi ed è il test da richiedere nel sospetto di feocromocitoma. Le metanefrine (metanefrina e normetanefrina) possono essere misurate nel plasma o nelle urine delle 24 ore. Il dosaggio plasmatico si accompagna alla facilità di raccolta del campione e a una maggior specificità, ma risulta più problematico per i bassi livelli di metanefrine circolanti. Il dosaggio nelle urine, dove le concentrazioni sono maggiori, risulta più facile, ma è meno specifico per possibili interferenze alimentari e comporta il problema della corretta raccolta del campione. A tutt'oggi esistono metodi di dosaggio immunologici, metodi in high performance liquid chromatography (HPLC) con detector elettrochimico o fluorimetrico e in spettrometria di massa tandem (LC-MS/MS). I primi, di più facile esecuzione, non sembrano offrire sufficiente accuratezza. Le misure in HPLC offrono risultati analitici migliori. La LC-MS/MS costituisce il gold standard e si avvia ad essere la misura di riferimento nel prossimo futuro.
L'Endocrinologo, 2000
L' enzima steroidi 5α-riduttasi, che comprende due isoenzimi denominati tipo 1 e tipo 2, ha un ru... more L' enzima steroidi 5α-riduttasi, che comprende due isoenzimi denominati tipo 1 e tipo 2, ha un ruolo fondamentale nel metabolismo degli androgeni poiché catalizza la conversione del testosterone in diidrotestosterone (DHT). Il DHT è l'androgeno più potente dell'organismo e svolge un ruolo fisiologico fondamentale nella differenziazione sessuale e nello sviluppo dei
L'Endocrinologo, 2003
L' irsutismo si definisce come la presenza, nella donna, di peli eccessivi in zone corporee e con... more L' irsutismo si definisce come la presenza, nella donna, di peli eccessivi in zone corporee e con caratteristiche tipiche dell'uomo (peli terminali in aree sessuali). Insieme all'acne e all'alopecia, è la manifestazione di una aumentata produzione o alterata funzionalità degli androgeni. A parità di livelli androgenici, la severità dei sintomi è molto diversa da paziente a paziente e alcune
American Journal of Physiology-Endocrinology and Metabolism, 2019
Metabolic syndrome (MetS) clusters cardiovascular and metabolic risk factors along with hypogonad... more Metabolic syndrome (MetS) clusters cardiovascular and metabolic risk factors along with hypogonadism and erectile dysfunction. Lifestyle modifications including physical exercise (PhyEx) are well-known treatments for this condition. In this study, we analyzed the effect of PhyEx on hypothalamic-pituitary-testis axis and erectile function by use of an animal MetS model, previously established in rabbits fed a high-fat diet (HFD). Rabbits fed a regular diet (RD) were used as controls. A subset of both groups was trained on a treadmill. HFD rabbits showed typical MetS features, including HG (reduced T and LH) and impairment of erectile function. PhyEx in HFD rabbits completely restored plasma T and LH and the penile alterations. At testicular and hypothalamic levels, an HFD-induced inflammatory status was accompanied by reduced T synthesis and gonadotropin-releasing hormone (GnRH) immunopositivity, respectively. In the testis, PhyEx normalized HFD-related macrophage infiltration and in...
Journal of Chromatography B: Biomedical Sciences and Applications, 1995
Finasteride is a potent inhibitor of the enzyme steroid 5a-reductase now approved as a drug for t... more Finasteride is a potent inhibitor of the enzyme steroid 5a-reductase now approved as a drug for the treatment of benign prostatic hyperplasia. We describe an original method for the quantitative determination of finasteride at picogram level in human plasma by isotope-dilution gas chromatography mass spectrometry. 5,6,6-[2H3]Finasteride was synthesized with an high ratio of trideuteration (finasteride/[2H3]finasteride = 0.007) allowing its optimal use as internal standard. Plasma samples were purified in a single-step procedure on solid-phase extraction C~8 columns with a recovery />90%. Samples were injected in the GC-MS instrument without any derivatization and the minimum detection level of finasteride was 50 pg with a signal-to-noise ratio of 6:1. The coefficients of variation for the 5 and 10 ng/ml (plasma) concentrations were 5.8% and 4%, respectively. The method has been applied to the determination of the plasma pharmacokinetic of finasteride in five male volunteers treated with a single 5-mg dose of the drug, affording kinetic parameters which are in good agreement with the values previously reported with a different methodology. The present method results accurate, specific, sensible and reliable for a routinely determination of finasteride at picogram levels.
The Endocrine Society's 93rd Annual Meeting & Expo, June 4–7, 2011 - Boston, 2011
Diagnostic Pathology, 2016
Background: Carbonic anhydrase IX is a member of α-carbonic anhydrases that is preferentially exp... more Background: Carbonic anhydrase IX is a member of α-carbonic anhydrases that is preferentially expressed in solid tumors. It enables bicarbonate transport across the plasma membrane, neutralizing intracellular pH and conferring to cancer cells a survival advantage in hypoxic/acidic microenvironments. Overexpression of carbonic anhydrase IX in cancer tissues is regulated by hypoxia inducible factor 1α − mediated transcription and the enzyme is considered a marker of tumor hypoxia and poor outcome. The role of carbonic anhydrase IX in prostate cancer has not been fully clarified and controversy has arisen on whether this enzyme is overexpressed in hypoxic prostate cancer tissues. Methods: We analyzed the expression of carbonic anhydrase IX and hypoxia inducible factor 1α in two prostate cancer cell lines, LNCaP and PC-3, and in 110 cancer biopsies, by western blotting and immunocyto/histochemistry. Results: In LNCaP and PC-3 cells, carbonic anhydrase IX was mostly cytoplasmic/nuclear, with very limited membrane localization. Nuclear staining became stronger under hypoxia. When we analyzed carbonic anhydrase IX expression in human prostate cancer biopsies, we found that protein staining positively correlated with hypoxia inducible factor 1α and with Gleason pattern and score, as well as with the novel grading system proposed by the International Society of Urological Pathology for prostate cancer. Once more, carbonic anhydrase IX was mainly cytoplasmic in low grade carcinomas, whereas in high grade tumors was strongly expressed in the nucleus of the neoplastic cell. An association between carbonic anhydrase IX expression level and the main clinic-pathological features involved in prostate cancer aggressiveness was identified. Conclusions: There was a statistically significant association between carbonic anhydrase IX and hypoxia inducible factor 1α in prostate cancer tissues, that identifies the enzyme as a reliable marker of tumor hypoxia. In addition, carbonic anhydrase IX expression positively correlated with prostate cancer grading and staging, and with outcome, suggesting that the protein may be an independent prognosticator for the disease. The nuclear translocation of the enzyme in hypoxic cancer cells may epitomize a biological switch of the tumor towards a less favorable phenotype.
J Steroid Biochem Mol Biol, 2004
Journal of the Chemical Society, Perkin Transactions 1, 1989
Journal of Endocrinological Investigation, 2001
The inhibitors of 5α-reductase isoenzymes (1 and 2) can be schematically divided in three groups ... more The inhibitors of 5α-reductase isoenzymes (1 and 2) can be schematically divided in three groups according they substrate specificity: a) pure or preferential inhibitor of 5α-reductase 1; b) pure or preferential inhibitor of 5α-reductase 2; c) dual inhibitors. Despite the fact that several steroidal and non-steroidal inhibitors have been synthesized and experimented in pharmacological models, only finasteride has been extensively used for clinical purposes. The largest application of finasteride in man has been human benign prostative hyperplasia (BPH). In addition, finasteride has been recently used for treatment of male baldness with a 50% of objective response. In women, finasteride has been used in some control trials for treatment of hirsutism with an objective favorable response. In conclusion, finasteride appears be useful for BPH, baldness and hirsutism (with caution) treatment. On the basis of experimental observations on distribution of 1 and 2 isoenzymes in human skin, scalp and prostate, the dual inhibitors should be more indicated for treatment of BPH and baldness. Similarly, the dual inhibitors seem indicated in attempting to prevent prostatic cancer. The pure 5α-reductase 1 inhibitors seem the ideal drugs for treatment of acne and hirsutism.