R Pasquali

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

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Publications (166)693.16 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.
    No preview · Article · Aug 2015 · Journal of endocrinological investigation
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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 ...
    Full-text · Article · Apr 2015 · Journal of endocrinological investigation
  • F. Guaraldi · R. Pasquali

    No preview · Article · Mar 2015
  • F. Guaraldi · R. Pasquali

    No preview · Article · Mar 2015
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    ABSTRACT: Along the years a troubled history featured the pharmacological therapy of obesity. Numerous once-promising weight-loss drugs have been abandoned because of a series of concomitant deleterious side effects. The recent withdrawn from the market of sibutramine and rimonabant is indeed a spectacular demonstration of the difficulties to obtain efficient safe weight-loss drugs devoid of any (or minimal) toxic effects. Nowadays, the approach to the pharmacological treatment of obesity is still based upon few traditional and historical drugs. In particular, the drugs currently approved by FDA are working mainly via the serotoninergic and noradrenergic pathways such as lorcaserin and phentermine/topiramate. Nevertheless, one should take in mind that a concomitant disagreement in the efficacy assessment of these drugs recently occurred between American and European agencies.
    No preview · Article · Jan 2015
  • J. Guidi · G. Tomei · A. Gambineri · E. Tomba · R. Pasquali · G. A. Fava

    No preview · Conference Paper · Jan 2015
  • 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.
    No preview · Article · May 2014 · Nature Reviews Endocrinology
  • F. Guaraldi · R. Pasquali

    No preview · Article · May 2014 · Journal of endocrinological investigation
  • F. Guaraldi · R. Pasquali

    No preview · Article · Apr 2014 · Journal of endocrinological investigation
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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.
    No preview · Article · Mar 2014
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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.
    Full-text · Article · Oct 2013 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: 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.
    No preview · Article · Oct 2013
  • 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.
    No preview · Article · Sep 2013 · Journal of endocrinological investigation
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    ABSTRACT: STUDY QUESTIONIs 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 ANSWERThe rs727428 and rs6259 variants are associated with PCOS in Mediterranean women. WHAT IS KNOWN ALREADYThe 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 DURATIONThis 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 CHANCEMutant 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 CAUTIONThe 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 FINDINGSSHBG 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 Investigación Carlos III, Spanish Ministry of Economy and Competitiveness. CIBERDEM is also an initiative of Instituto de Investigación Carlos III. The Authors have no competing interests to declare.
    Preview · Article · Nov 2012 · Human Reproduction
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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.
    Full-text · Article · Aug 2012 · Cell cycle (Georgetown, Tex.)
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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?
    Full-text · Article · Jul 2012 · Human Reproduction
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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.
    Full-text · Article · Jun 2012 · Orphanet Journal of Rare Diseases
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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.
    Preview · Article · May 2012 · Annals of the New York Academy of Sciences
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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.
    No preview · Article · Feb 2012 · Human Reproduction
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    Full-text · Article · Oct 2011 · 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

Publication Stats

9k Citations
693.16 Total Impact Points

Institutions

  • 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
      • • Department of Experimental, Diagnostic and Specialty Medicine DIMES
      Bolonia, Emilia-Romagna, Italy
  • 2011
    • Johns Hopkins Medicine
      • Department of Pathology
      Baltimore, MD, United States
  • 2000
    • Azienda Unità Sanitaria Locale di Bologna
      Bolonia, Emilia-Romagna, Italy
  • 1991
    • Università degli Studi di Genova
      Genova, Liguria, Italy