R Pasquali

Policlinico S.Orsola-Malpighi, Bolonia, Emilia-Romagna, Italy

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Publications (159)677.06 Total impact

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    ABSTRACT: 11β-Hydroxylase deficiency (11OHD) represents the second most common cause of congenital adrenal hyperplasia. It is caused by mutations in the CYP11B1 gene localized about 40 kb from the CYP11B2 gene with which it shares a homology of 95 %. The asymmetric recombination of these two genes is involved both in 11OHD and in glucocorticoid-remediable aldosteronism (GRA). Our objective was to set up an easy and rapid method to detect these hybrid genes and other kinds of deletions, to improve the molecular diagnosis of 11OHD. A set of 8 specific probes for both the CYP11B1 and the CYP11B2 genes to be used for multiplex ligation-dependent probe amplification (MLPA) analysis was designed to detect rearrangements of these genes. The method developed was tested on 15 healthy controls and was proved to be specific and reliable; it led us to identify a novel chimeric CYP11B2/CYP11B1 gene in one patient that carried the known A306V mutation on the other allele. Specific amplification and sequencing of the hybrid gene confirmed the breakpoint localization in the second intron. The MLPA kit developed enables the detection of deletions, duplications or chimeric genes and represents an optimal supplement to DNA sequence analysis in patients with 11OHD. In addition, it can also be used to show the presence of the opposite chimaera associated with GRA.
    Journal of endocrinological investigation 08/2015; DOI:10.1007/s40618-015-0362-z · 1.45 Impact Factor
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    P Moghetti · E Carmina · V De Leo · A Lanzone · F Orio · R Pasquali · V Toscano
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    ABSTRACT: IntroductionReproductive alterations are a mainstay of the classic definition of polycystic ovary syndrome (PCOS), as defined in 1992 by the NIH consensus statement on PCOS [1]. These abnormalities still represent one of the three cardinal aspects used for diagnosing PCOS according to the current criteria, as defined by the Rotterdam ESHRE/ASRM consensus workshop [2] and by the AE-PCOS Society [3]. In addition, the reproductive alterations of PCOS are a key point in the treatment of this condition.Although there are several guidelines on the management of infertility in PCOS women, this issue remains controversial. Moreover, most of the documents on this topic were produced, by both the human reproduction societies and the endocrinology societies, with pregnancy as an immediate objective. However, reproductive abnormalities are frequently a central problem in these women beyond this specific aim, and come before and after this goal. Physicians are thus called to manage the reproductive ...
    Journal of endocrinological investigation 04/2015; 38(9). DOI:10.1007/s40618-015-0274-y · 1.45 Impact Factor
  • Renato Pasquali
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    ABSTRACT: Polycystic ovary syndrome is often associated with complications in pregnancy, which metformin does not seem to ameliorate. A recent study has investigated insulin levels in the umbilical venous blood (maternal levels) and umbilical arterial blood (fetal levels). The data seem to suggest the placenta is involved in insulin secretion during pregnancy.
    Nature Reviews Endocrinology 05/2014; 10(7). DOI:10.1038/nrendo.2014.61 · 13.28 Impact Factor
  • F. Guaraldi · R. Pasquali
    Journal of endocrinological investigation 05/2014; 34(5):410-410. DOI:10.1007/BF03347467 · 1.45 Impact Factor
  • F. Guaraldi · R. Pasquali
    Journal of endocrinological investigation 04/2014; 33(4):286-286. DOI:10.1007/BF03345795 · 1.45 Impact Factor
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    ABSTRACT: Aims To provide a reference standard database of ultrasonographic parameters of abdominal adiposity in healthy people. Methods Italian non-obese volunteers among blood donors were enrolled in 5 age bands (from 18 to 70 year-old) to reach the threshold of 25 males and 25 females per single band (total: 250). All subjects were measured for weight, height and waist circumference and underwent ultrasonography (US) by an expert radiologist for the assessment of several abdominal fat thicknesses (minimum and maximum subcutaneous fat thickness, maximum preperitoneal fat thickness, intrabdominal fat thickness, aorto-mesenteric thickness, and mesenteric fat thickness). In addition, US data were normalized per waist circumference. Results From 30s to 50s no statistically significant differences were achieved between males and females for the adiposity markers of visceral fat, while a relevant divergence was proved from 60s to 70s. During ageing a marked increase of the visceral fat compartment was observed in males, while only the preperitoneal circumference was significantly modified in females. Conclusions This paper reports on US parameters of abdominal adiposity of healthy Italian adults, to be used as a reference for daily clinical practice. Data could be also considered as control group for future investigations on physiology, pathological conditions, and differences between countries.
    03/2014; 8(4). DOI:10.1016/j.pcd.2014.02.003
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    ABSTRACT: Context:Polycystic ovary syndrome (PCOS) is a prevalent disorder that affects childbearing age women and may be related to obesity and insulin resistance.Objective:To appraise the evidence of the impact of lifestyle modification (LSM) interventions on outcomes of women with PCOS.Data sources:Sources included Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo and CINAHL (Until January 2011).Study Selection:We included randomized controlled trials (RCTs) that enrolled woman of any age with PCOS who received LSM and compared them against women who received no intervention, minimal intervention or metformin.Data extraction:Two authors performed the data extraction independently.Data synthesis:We included 9 trials enrolling 583 women with high loss to follow-up rate, lack of blinding and short follow up. Compared to minimal intervention, LSM significantly reduced fasting blood glucose (weighted mean difference (WMD) -2.3 mg/dL, 95% confidence intervals (CI) -4.5 to -0.1, I(2) = 72%, p=0.04) and fasting blood insulin (WMD -2.1 μU/mL, 95% CI -3.3 to -1.0, I(2) = 0%, p<0.001). Change in body mass index was associated with changes in fasting blood glucose (p<0.001). Metformin was not significantly better than LSM in improving blood glucose or insulin levels. We found no significant effect of LSM on pregnancy rate and the effect on hirsutism was unclear.Conclusions:The available evidence suggests that LSM reduce fasting blood glucose and insulin levels in women with PCOS. Metformin has similar effects. Translation of these short-term effects to patient-important outcomes - beyond diabetes prevention, remains uncertain.
    The Journal of Clinical Endocrinology and Metabolism 10/2013; 98(12). DOI:10.1210/jc.2013-2385 · 6.21 Impact Factor
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    ABSTRACT: What is already known about this subject: Obesity is an increasingly prevalent metabolic disorder and it is associated with a large number of comorbidities, including cardiovascular diseases. Adipose tissue is an active endocrine organ and its ectopic depots and distribution have different metabolic meanings on risks for health; as a matter of fact, epicardial fat seems to play a specific role in cardiovascular diseases. The use of dual-energy X-ray absorptiometry (DXA) to evaluate and follow-up patients affected by obesity is becoming a very important point in the management of the disease. What this study adds: An investigation of the association between epicardial fat and regional adiposity by DXA in female obese patients. The total amount of central (trunk) fat mass is more strongly correlated than android visceral fat mass to epicardial thickness in obese women. In the interpretation of whole-body DXA data, physician should consider trunk fat mass for good and independent predictivity on epicardial fat depots. Our aim was to analyse in a population of obese women the relationship between the amount of epicardial fat as measured by transthoracic echocardiography (US) and the parameters of regional adiposity by dual-energy X-ray absorptiometry (DXA), with particular reference to a new software for visceral fat assessment and to a new 'heart-suited' regions of interests (ROIs). Sixty patients who satisfied technical inclusion criteria underwent whole-body DXA scan and US on the same day. Total and android fat mass (FM) and FM percentage (FM%) were considered as well as visceral fat (VAT) subcompartment in the android region; moreover, six new ROIs were designed on whole-body DXA images for the investigation of adiposity parameters at heart level. US provided epicardial fat thickness (EPI-thickness) and area (EPI-area), as measured following previously validated methods. Body mass index (BMI), gynoid and lower limbs (FM and FM%) were found not statistically correlated with EPI-thickness. The highest correlation was achieved by trunk FM (and FM%, with r = 0.544 and 0.480 respectively, P < 0.001), followed by ROI-1 FM (ROI-1 was drawn following thoroughly the cardiac profile), and android FM. Multivariate analysis including age, weight, BMI, trunk FM and the new ROIs (added one by one), retained in the final model trunk FM. Correlations of DXA with EPI-area were superimposable. In obese women, VAT or other new-designed ROIs are not better correlated than traditional ROIs (i.e. trunk) with epicardial fat amount.
    10/2013; 3(5). DOI:10.1111/cob.12027
  • R Pasquali · A Gambineri
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    ABSTRACT: The polycystic ovary syndrome (PCOS), the most common hyperandrogenic disorder affecting 4-7% of women, is often associated with metabolic alterations, chiefly insulin resistance and obesity. Based on available scientific evidence, PCOS should be regarded as an independent risk for the development of glucose intolerance states. This short review summarizes the available literature on the prevalence and incidence of impaired glucose tolerance and Type 2 diabetes in this disorder. In addition, some insights on potential factors responsible for individual susceptibility are discussed. Targeted intervention studies focused on prevention and treatment of glucose intolerance states in PCOS are warranted.
    Journal of endocrinological investigation 09/2013; 36(8):648-653. DOI:10.1007/BF03346757 · 1.45 Impact Factor
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    ABSTRACT: STUDY QUESTION: Is there an association between polycystic ovary syndrome (PCOS) and the sex hormone-binding globulin (SHBG) rs1799941, rs6257, rs6259 and rs727428 variants in a large series of Mediterranean women? SUMMARY ANSWER: The rs727428 and rs6259 variants are associated with PCOS in Mediterranean women. WHAT IS KNOWN ALREADY: The level of SHBG, the primary plasma transport protein for sex steroids, which regulates the bioavailability of these hormones to target tissues, is reduced in patients with PCOS. Single-nucleotide polymorphisms in the SHBG gene influence circulating SHBG levels in American patients with PCOS and may predict the development of type 2 diabetes. STUDY DESIGN, SIZE AND DURATION: This was a genetic case-control association study including 1004 premenopausal Mediterranean women. PARTICIPANTS/MATERIALS, SETTING AND METHODS: In an Academic setting, we genotyped a clinical cohort consisting of 281 patients with PCOS and 142 women without any evidence of androgen excess, and a population-based cohort comprised of 581 unselected female blood donors from Spain and Italy. The latter included 31 patients with PCOS and 550 controls, of whom 298 had no evidence of any androgen excess disorder and were considered hyper-normal controls. MAIN RESULTS AND THE ROLE OF CHANCE: Mutant alleles of the rs727428 variant were more frequent in patients with PCOS compared with controls and with hyper-normal controls. This association was independent of obesity. Carrying mutant alleles of rs727428 was found to be associated with a 1.29 odds ratio (OR) for PCOS, whereas carrying mutant alleles of rs6259 associated with a 0.68 OR for PCOS. The rs1799941 and rs6257 variants were not associated with PCOS. None of the SHBG variants influenced serum SHBG concentrations. LIMITATIONS AND REASONS FOR CAUTION: The associations found here were relatively weak and, arising from a case-control study, do not necessarily indicate a causative role of the SHBG variants in the development of PCOS. Also, we studied different patients and controls from different sources, making some of the interpretations difficult. Finally, the rs1799941 variant was not in Hardy-Weinberg equilibrium in the small group of patients with PCOS recruited from the general population, yet this variant was not associated with PCOS. WIDER IMPLICATIONS OF THE FINDINGS: SHBG variants that influenced circulating SHBG levels in American patients with PCOS are also associated with this syndrome in Mediterranean women, pointing to SHBG as a candidate gene for PCOS. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants PI080944 and PI110357 from Instituto de Investigacion Carlos III, Spanish Ministry of Economy and Competitiveness. CIBERDEM is also an initiative of Instituto de Investigacion Carlos III. The Authors have no competing interests to declare.
    Human Reproduction 11/2012; 27(12-12):3569-76. DOI:10.1093/humrep/des335 · 4.57 Impact Factor
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    ABSTRACT: Prelamin A processing impairment is a common feature of a restricted group of rare genetic alterations/disorders associated with a wide range of clinical phenotypes. Changes in histone posttranslational modifications, alterations in non-histone chromatin proteins and chromatin disorganization have been specifically linked to impairment of specific, distinct prelamin A processing steps, but the molecular mechanism involved in these processes is not yet understood . In this study, we show that the accumulation of wild-type prelamin A detected in restrictive dermopathy (RD), as well as the accumulation of mutated forms of prelamin A identified in familial partial lipodystrophy (FPLD) and mandibuloacral dysplasia (MADA), affect the nuclear localization of barrier-to-autointegration factor (BAF), a protein able to link lamin A precursor to chromatin remodeling functions. Our findings, in accordance with previously described results, support the hypothesis of a prelamin A involvement in BAF nuclear recruitment and suggest BAF-prelamin A complex as a protein platform usually activated in prelamin A-accumulating diseases. Finally, we demonstrate the involvement of the inner nuclear membrane protein emerin in the proper localization of BAF-prelamin A complex.
    Cell cycle (Georgetown, Tex.) 08/2012; 11(19):3568-77. DOI:10.4161/cc.21869 · 4.57 Impact Factor
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    ABSTRACT: STUDY QUESTION: Do different dosages of metformin account for different clinical and biochemical outcomes in women with polycystic ovary syndrome (PCOS) and do basal anthropometric and metabolic characteristics of the patients provide any indications regarding the dose required to reach the target effect? SUMMARY ANSWER: Different doses of metformin exerted the same effects on clinical, biochemical and metabolic parameters in patients affected by PCOS. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Since the insulin-sensitizing agents came into use in the management of PCOS, metformin has shown a positive benefits-risks ratio. Nonetheless, therapeutic schedules are not well standardized. This is the first study which systematically analyses the effect of different doses of metformin on clinical, hormonal and metabolic features of PCOS. On the basis of our results, higher doses are no more effective than lower doses. DESIGN: A multicentric cohort prospective study. A total of 250 PCOS women were enrolled, 49 lost to follow-up. Menstrual cyclicity, hormonal assays, oral glucose tolerance test, lipid profile and ultrasonographic pelvic examination were evaluated at the baseline and after 6 months of metformin treatment at different doses (1000, 1500 and 1700 mg). PARTICIPANTS AND SETTING: A total of 201 PCOS patients completed the study without protocol violations in three university hospitals: seventy-three patients from Centre A (treated with metformin 500 mg twice a day), 60 patients from Centre B (treated with metformin 500 mg three times a day) and 68 patients from Centre C (treated with metformin 850 mg twice a day). MAIN RESULTS AND THE ROLE OF CHANCE: Metformin exerted an overall positive effect on the clinical and endocrine-metabolic features of PCOS. The degree of these effects was independent of the administered dosage in every range of basal body mass index (BMI). When patients were stratified according to their insulinaemic status, scattered inter-doses differences were found in some of the outcome measures. Patients who exhibited an increase of >2 menstrual cycles/year were considered as responders to treatment. Responders had a higher basal BMI than non-responders and showed a greater reduction in plasma testosterone levels after metformin treatment, but other outcome measures did not differ significantly. Total insulin secretion in the 180 min following the glucose tolerance test before metformin treatment (basal AUC-I) was significantly correlated with the decrease in insulin secretion induced by metformin in both the whole group and in responders, but only correlated with the variation in the number of cycles in responders. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: The different doses were administered in different centres, and between-centre variation is a potential confounding factor. GENERALIZABILITY TO OTHER POPULATIONS: The paradigm of using the minimum effective dose of metformin could be pursued in other pathological conditions characterized by insulin resistance. STUDY FUNDING/COMPETING INTEREST(S): No funding or competing interests to declare.
    Human Reproduction 07/2012; 27(10):3057-66. DOI:10.1093/humrep/des262 · 4.57 Impact Factor
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    ABSTRACT: The need for a collaborative approach to complex inherited diseases collectively referred to as laminopathies, encouraged Italian researchers, geneticists, physicians and patients to join in the Italian Network for Laminopathies, in 2009. Here, we highlight the advantages and added value of such a multidisciplinary effort to understand pathogenesis, clinical aspects and try to find a cure for Emery-Dreifuss muscular dystrophy, Mandibuloacral dysplasia, Hutchinson-Gilford Progeria and forms of lamin-linked cardiomyopathy, neuropathy and lipodystrophy.
    Orphanet Journal of Rare Diseases 06/2012; 7(1):37. DOI:10.1186/1750-1172-7-37 · 3.36 Impact Factor
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    Renato Pasquali
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    ABSTRACT: Obesity, particularly the abdominal phenotype, has been ascribed to an individual maladaptation to chronic environmental stress exposure mediated by a dysregulation of related neuroendocrine axes. Alterations in the control and action of the hypothalamic-pituitary-adrenal axis play a major role in this context, with the participation of the sympathetic nervous system. The ability to adapt to chronic stress may differ according to sex, with specific pathophysiological events leading to the development of stress-related chronic diseases. This seems to be influenced by the regulatory effects of sex hormones, particularly androgens. Stress may also disrupt the control of feeding, with some differences according to sex. Finally, the amount of experimental data in both animals and humans may help to shed more light on specific phenotypes of obesity, strictly related to the chronic exposure to stress. This challenge may potentially imply a different pathophysiological perspective and, possibly, a specific treatment.
    Annals of the New York Academy of Sciences 05/2012; 1264(1):20-35. DOI:10.1111/j.1749-6632.2012.06569.x · 4.38 Impact Factor
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    ABSTRACT: The polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. On the contrary, the prevalences of other disorders of androgen excess such as idiopathic hyperandrogenism and idiopathic hirsutism remain unknown. We aimed to obtain an unbiased estimate of the prevalence in premenopausal women of (i) signs of androgen excess and (ii) PCOS, idiopathic hyperandrogenism and idiopathic hirsutism. A multicenter prevalence survey included 592 consecutive premenopausal women (393 from Madrid, Spain and 199 from Bologna, Italy) reporting spontaneously for blood donation. Immediately before donation, we conducted clinical and biochemical phenotyping for androgen excess disorders. We determined the prevalence of (i) hirsutism, acne and alopecia as clinical signs of androgen excess and (ii) functional disorders of androgen excess, including PCOS, defined by the National Institute of Child Health and Human Development/National Institute of Health criteria, idiopathic hyperandrogenism and idiopathic hirsutism. Regarding clinical signs of hyperandrogenism, hirsutism and acne were equally frequent [12.2% prevalence; 95% confidence interval (CI): 9.5-14.8%], whereas alopecia was uncommon (1.7% prevalence, 95% CI: 0.7-2.7%). Regarding functional disorders of androgen excess, PCOS and idiopathic hirsutism were equally frequent (5.4% prevalence, 95% CI: 3.6-7.2) followed by idiopathic hyperandrogenism (3.9% prevalence, 95% CI: 2.3-5.4). Clinical signs of hyperandrogenism and functional disorders of androgen excess show a high prevalence in premenopausal women. The prevalences of idiopathic hyperandrogenism and idiopathic hirsutism are similar to that of PCOS, highlighting the need for further research on the pathophysiology, consequences for health and clinical implications of these functional forms of androgen excess.
    Human Reproduction 02/2012; 27(4):1209-16. DOI:10.1093/humrep/des028 · 4.57 Impact Factor
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    Acta myologica: myopathies and cardiomyopathies: official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases 10/2011; 30(2):138-43.
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    Acta myologica: myopathies and cardiomyopathies: official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases 09/2011; 30(2):159-159.
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    ABSTRACT: The aims of the study were to understand the association between insulin-like factor 3 (INSL3) and functional ovarian hyperandrogenism (FOH) in PCOS and the regulatory role played by LH. Fifteen PCOS women were classified as FOH (FOH-PCOS, no.=8) and non-FOH (NFOH-PCOS, no.=7) according to the response of 17OH-progesterone to buserelin (a GnRH analogue) with respect to 15 controls. FOH-PCOS and NFOH-PCOS were compared for basal INSL3 levels. In addition, the effect of buserelin on INSL3 concentrations and the relationship between basal and buserelin-stimulated LH and 17OH-progesterone and INSL3 were evaluated. Basal INSL3 levels were higher in FOH-PCOS than NFOH-PCOS (p=0.001) and controls (p=0.001), whereas they did not differ between NFOHPCOS and controls. In addition, FOH-PCOS had a higher response of LH to buserelin with respect to NFOH-PCOS. Within all PCOS women the levels of INSL3 positively correlated with free testosterone (p=0.022) and negatively with SHBG (r= p=0.031). Moreover, positive correlations with the absolute increase of 17OH-progesterone (p<0.001) and with the LH area under the curve (p=0.001) after buserelin administration were found. In the multiple regression analysis INSL3 persisted significantly correlated only with 17OH-progesterone response to buserelin. Finally, INSL3 was not significantly modified after buserelin administration either in FOHPCOS or in NFOH-PCOS. These data suggest that INSL3 is related to FOH in PCOS women, but this association seems not to be mediated by LH, further reinforcing the concept that a pathophysiological heterogeneity for ovarian hyperandrogenism in PCOS exists.
    Journal of endocrinological investigation 05/2011; 34(9):685-91. DOI:10.3275/7726 · 1.45 Impact Factor
  • F Guaraldi · R Pasquali
    Journal of endocrinological investigation 05/2011; 34(5):410. · 1.45 Impact Factor
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    ABSTRACT: Testosterone administered alone or in combination with progestogens in male contraception induces reversible oligo-azoospermia, but its effects on body composition and metabolism are less known. We analysed anthropometric and metabolic parameters in five groups of 10 males: four receiving testosterone undecanoate (TU: 1000 mg) plus norethisterone enanthate (NETE: 200 mg) at different intervals (every 8 weeks: NETE-8; every 12 weeks: NETE-12; every 6 weeks for 12 weeks and then every 12 weeks: NETE-6/12; every 6 weeks for 12 weeks and then TU plus placebo every 12 weeks: NETE-6/12/0) and one placebo (NETE-0/0) for a total of 48 weeks. Body mass index (BMI) and waist circumference did not change in any groups except for the NETE-8 in which BMI increased significantly (p = 0.02) at the end of the treatment period. Lean body mass (MAMC or AMA) increased significantly in the highest hormonal dose groups (p = 0.04, NETE-6/12; p = 0.004, NETE-8). No differences were observed in glucose levels, insulin sensitivity index and lipid profile as well as in biochemical and cell count parameters in any groups. In conclusion, NETE and TU for 48 weeks were not accompanied by any metabolic changes and any adverse effects. The weight gain of the highest NETE plus TU dosage was mainly because of gain in muscle mass.
    International Journal of Andrology 11/2010; 34(6 Pt 1):548-55. DOI:10.1111/j.1365-2605.2010.01122.x · 3.70 Impact Factor

Publication Stats

7k Citations
677.06 Total Impact Points


  • 1997–2013
    • Policlinico S.Orsola-Malpighi
      Bolonia, Emilia-Romagna, Italy
  • 1981–2013
    • University of Bologna
      • • Department of Medical and Surgical Sciences DIMEC
      • • Division of Endocrinology
      • • Institute of Genetic Medicine
      Bolonia, Emilia-Romagna, Italy
  • 2011
    • Johns Hopkins Medicine
      • Department of Pathology
      Baltimore, MD, United States
  • 1991
    • Università degli Studi di Genova
      Genova, Liguria, Italy