Search tips
Search criteria

Results 1-6 (6)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
Endocrinology  2009;151(1):195-202.
Regeneration of active glucocorticoids within liver and adipose tissue by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) may be of pathophysiological importance in obesity and Metabolic Syndrome and is a therapeutic target in type 2 diabetes. Polymorphisms in HSD11B1, the gene encoding 11β-HSD1, have been associated with metabolic phenotype in humans, including type 2 diabetes and hypertension. Here we have tested the functional consequences of 2 single nucleotide polymorphisms located in contexts that potentially affect tissue levels of 11β-HSD1. We report no effect of allelic variation at rs846910, a polymorphism within the 5′-flanking region of the gene on HSD11B1 promoter activity in vitro. However, compared to the common G allele, the A allele of rs13306421, a polymorphism located 2 nucleotides 5′ to the translation initiation site, gave higher 11β-HSD1 expression and activity in vitro and was translated at higher levels in in vitro translation reactions, possibly associated with a lower frequency of “leaky scanning”. These data suggest that this polymorphism may have direct functional consequences on levels of 11β-HSD1 enzyme activity in vivo. However, the rs13306421 A sequence variant originally reported in other ethnic groups may be of low prevalence as it was not detected in a population of 600 European caucasian women.
PMCID: PMC3971150  PMID: 19934376
steroid metabolism; glucocorticoid; obesity; SNP; translation; regulation
2.  Personality and Psychiatric Disorders in Women Affected by Polycystic Ovary Syndrome 
Background: Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder among fertile women. Studies show reduced quality of life, anxiety, depression, body dissatisfaction, eating disorder, and sexual dysfunction, but the etiology of these disturbs remains still debated. The aim of our study is to verify whether this hyperandrogenic syndrome characterizes a strong psycho(patho)logical personality.
Method: Sixty PCOS subjects (mean age 25.8 ± 4.7 years) were evaluated by anthropometric, metabolic, hormonal, clinical, and psychological parameters. After the certainty of the diagnosis of PCOS, the Rorschach test, according to Exner’s comprehensive system (CS) and the Millon Clinical Multiaxial Inventory-III (MCMI-III) were administered to each patient. The control group, on which the comparison was carried out, was composed by 40 healthy and aged compared women who were exclusively administered the Rorschach test according to CS.
Results: MCMI-III evidenced axis II DSM-IV personality disorders [4.1% schizoid, depressive, sadistic, negativistic (passive–aggressive), and masochistic, 6.1% avoiding, 12.2% dependent, 20.4% histrionic, 16.3% narcissistic, 2.0% obsessive–compulsive], and axis I DSM-IV psychiatric disorders: 10.2% anxiety, 2.0% somatoform disorder and bipolar disorder, 16.3% major depressive disorder. Finally, we found 44.9% delusional disorder and 4.1% thought disorder. Rorschach test’s results show 53.1% reduced coping abilities and social skills, 55.1% depression, 30.6% perceptual distortion and cognitive slippage, 24.5% constantly alert and worry, 8.1% at risk for suicide, and finally about 50% of our patients had chronic stress.
Conclusion: PCOS women have relevant personality and psychiatric disorders, when compared with normal subjects.
PMCID: PMC4228916  PMID: 25429283
polycystic ovary syndrome; personality; Rorschach; MCMI-III; psychopathology; personality disorder; psychiatric disorder
3.  Polycystic Ovary Syndrome Is a Risk Factor for Type 2 Diabetes 
Diabetes  2012;61(9):2369-2374.
Polycystic ovary syndrome (PCOS) recently has been identified as a risk factor associated with type 2 diabetes. However, the evidence derives from cross-sectional observational studies, retrospective studies, or short-term prospective studies. This long-term prospective study of a large cohort of women with PCOS, followed from youth to middle age, aimed at estimating, for the first time, the incidence and potential predictors of type 2 diabetes in this population. A total of 255 women with PCOS were followed for at least 10 years (mean follow-up 16.9 years). Six women were patients with diabetes at baseline, and another 42 women developed type 2 diabetes during the follow-up. The incidence rate of type 2 diabetes in the study population was 1.05 per 100 person-years. The age-standardized prevalence of diabetes at the end of follow-up was 39.3%, which is significantly higher with respect to that of the general Italian female population of a similar age (5.8%). The likelihood of developing type 2 diabetes significantly increased as BMI, fasting glucose, and glucose area under the curve at baseline increased and significantly decreased as sex hormone–binding globulin (SHBG) levels at follow-up increased. This study demonstrates that the risk of type 2 diabetes is markedly elevated in middle-aged women with PCOS and suggests including BMI, glucose, and SHBG-circulating levels in the risk stratification.
PMCID: PMC3425413  PMID: 22698921
4.  Familial partial lipodystrophy, mandibuloacral dysplasia and restrictive dermopathy feature barrier-to-autointegration factor (BAF) nuclear redistribution 
Cell Cycle  2012;11(19):3568-3577.
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.
PMCID: PMC3478308  PMID: 22935701
BAF; BANF1; prelamin A; lamin A/C; laminopathies; emerin; EDMD1
5.  The empowerment of translational research: lessons from laminopathies 
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.
PMCID: PMC3458975  PMID: 22691392
Laminopathies; Emery-Dreifuss Muscular Dystrophy; Dilated Cardiomyopathy with Conduction Defects; Mandibuloacral Dysplasia; Familial Partial Lipodystrophy Type 2; Hutchinson-Gilford Progeria Syndrome; Rare Diseases; Networking activity; interdisciplinary approach to diseases
6.  Mitochondrial Oxidative Phosphorylation Is Impaired in Patients with Congenital Lipodystrophy 
Lipid accumulation in skeletal muscle and the liver is strongly implicated in the development of insulin resistance and type 2 diabetes, but the mechanisms underpinning fat accrual in these sites remain incompletely understood. Accumulating evidence of muscle mitochondrial dysfunction in insulin-resistant states has fuelled the notion that primary defects in mitochondrial fat oxidation may be a contributory mechanism. The purpose of our study was to determine whether patients with congenital lipodystrophy, a disorder primarily affecting white adipose tissue, manifest impaired mitochondrial oxidative phosphorylation in skeletal muscle.
Research Design and Methods:
Mitochondrial oxidative phosphorylation was assessed in quadriceps muscle using 31P-magnetic resonance spectroscopy measurements of phosphocreatine recovery kinetics after a standardized exercise bout in nondiabetic patients with congenital lipodystrophy and in age-, gender-, body mass index-, and fitness-matched controls.
The phosphocreatine recovery rate constant (k) was significantly lower in patients with congenital lipodystrophy than in healthy controls (P < 0.001). This substantial (∼35%) defect in mitochondrial oxidative phosphorylation was not associated with significant changes in basal or sleeping metabolic rates.
Muscle mitochondrial oxidative phosphorylation is impaired in patients with congenital lipodystrophy, a paradigmatic example of primary adipose tissue dysfunction. This finding suggests that changes in mitochondrial oxidative phosphorylation in skeletal muscle could, at least in some circumstances, be a secondary consequence of adipose tissue failure. These data corroborate accumulating evidence that mitochondrial dysfunction can be a consequence of insulin-resistant states rather than a primary defect. Nevertheless, impaired mitochondrial fat oxidation is likely to accelerate ectopic fat accumulation and worsen insulin resistance.
PMCID: PMC3380089  PMID: 22238385

Results 1-6 (6)