Combined evaluation of prolactin-induced peptide (PIP) and extracellular signal-regulated kinase (ERK) as new sperm biomarkers of FSH treatment efficacy in normogonadotropic idiopathic infertile men.

PURPOSE: Nearly, 40% of the causes of male infertility remain idiopathic. The only suggested treatment in idiopathic oligo- and/or asthenozoospermia in normogonadotropic patients is the FSH. In the current clinical practice, efficacy is exclusively assessable through semen analysis after 3 months of treatment. No molecular markers of treatment efficacy are appliable in clinical practice. The aim of the present work is to evaluate the combination of extracellular signal regulated kinase (ERK) 1 and 2 and prolactin inducible peptide (PIP) as potential markers of idiopathic infertility and FSH treatment efficacy. METHODS: Western blot and confocal microscopy were performed to analyze the modulation of PIP and ERK1/2 in idiopathic infertile patients (IIP) sperm cells. Taking advantage of mass spectrometry analysis, we identified these proteins unequivocally in sperm cells. RESULTS:  We demonstrated a significant decrease of both PIP protein and of ERK1/2 levels in spermatozoa obtained from IIP in comparison to healthy fertile patients (HFP). Conversely, we reported a significant increase of these markers comparing infertile patients before and after 3 months of FSH treatment. Importantly, this correlated with an increase in total number of sperm and sperm motility after FSH treatment. Finally, we identified of PIP and ERK2 proteins in sperm samples by proteomic analysis. CONCLUSIONS: The combined evaluation of ERK1/2 and PIP proteins might represent a useful molecular marker to tailor FSH treatment in the management of male normogonadotropic idiopathic infertility.

Stabilization vs. destabilization of G-quadruplex superstructures: the role of the porphyrin derivative having spermine arms.

The interaction of the porphyrin derivative H2TCPPSpm4, having spermine pendants in the four meso positions, with the G-quadruplex (GQ) structure formed by the DNA aptamer TGGGAG has been investigated by means of UV, electronic circular dichroism and PAGE studies. The results reported here demonstrate that the porphyrin derivative is capable of stabilizing or destabilizing the higher-ordered structures of parallel GQs, depending on the method used to reach their relative stoichiometry (titration vs. single addition). Noteworthily, when two equivalents of H2TCPPSpm4 were mixed directly with one equivalent of the (TGGGAG)4 GQ to reach a 2 : 1 H2TCPPSpm4 : GQ ratio T1/2 higher than 80 °C was also observed confirming the presence of higher-ordered GQ structures.

Neural correlates of fatigue in multiple sclerosis: a combined neurophysiological and neuroimaging approach (R1).

The present study is aimed at further exploring structural and functional correlates of fatigue in Relapsing- Remitting Multiple Sclerosis (RRMS) patients by using a combined approach by means of transcranial magnetic stimulation (TMS) and a Diffusion Tensor Imaging (DTI). The physiopathology of fatigue in MS is still poorly understood, although a variety of pathogenic mechanisms has been proposed. Our working hypothesis is that diffuse microstructural white matter damage may subtend the cortico-subcortical functional disconnection described in patients with MS and fatigue. We enrolled 30 RRMS patients (mean age 39±13; age range 24-63 years) with mild neurological impairment Expanded Disability Status Scale <3.5, divided into two groups on the basis of their fatigue severity scale (FSS) scoring (cutoff ≥ 4). All the patients underwent a neurological evaluation, a brain MRI acquisition (including DTI study) and a neurophysiological assessment by means of TMS in a pre-movement facilitation paradigm. Our data showed a significant mean diffusivity (MD) increase (p=0.036) in left thalamo-frontal reconstructions in the MS patients with fatigue compared to those classified as non-fatigued. Moreover, significant correlations were observed between FSS scale and MD as well as planar coefficient (CP) values extracted from frontal-thalamic connections bilaterally. Instead, the pre-movement facilitation showed a significant difference between the groups with particular regard to the Reaction Time- MEP50ms amplitude (p=0.03). Our work confirms that fatigue is associated with a disruption of brain networks involved in motor preparation processes, depending on several frontal-thalamic pathways. Such findings can have an important role when dealing with fatigue management in MS patients and could be eventually used as prognostic marker of MS course.

Growth hormone receptor isoforms and fracture risk in adult-onset growth hormone-deficient patients.

INTRODUCTION: Growth hormone deficiency is considered the most important factor determining skeletal fragility in hypopituitary patients. Osteoblasts and chondrocytes express growth hormone (GH) receptor. Two GH receptor isoforms (GHRi) have been identified: they differ for the presence/absence of a protein fragment encoded by exon 3 of GHR gene. Consequently, three genotypes were identified: carriers of both the full-length proteins (flfl-GHR), carriers of one full-length protein and one deleted protein (fld3-GHR) and carriers of both deleted proteins (d3d3-GHR). This polymorphism confers a higher sensitivity to endogenous GH and to recombinant human GH (rhGH); its effect on bone metabolism and skeletal fragility is unknown. The aim of this article was to investigate the role of GHRi in predicting skeletal fragility in adult-onset GHD (AO-GHD) patients. SUBJECTS AND METHODS: A cross-sectional study was conducted to investigate the association between the d3-GHR isoform and the prevalence of morphometric vertebral fractures (VFs) in AO-GHD. Ninety-three AO-GHD were enrolled. Forty-nine patients carried flfl-GHRi (52·7%), and 44 patients (47·3%) carried at least one allele of the d3-GHR isoform. Thirty-two VFs were documented. Fifty-seven patients underwent rhGH replacement therapy. RESULTS: Median age was significantly higher in fractured patients as compared to nonfractured ones; d3-carrier patients showed a lower VF risk as compared to flfl-GHRi (OR: 0·37, 95% IC: 0·24-0·55, P < 0·0001). This finding was also confirmed in AO-GHD undergoing rhGH replacement therapy. CONCLUSION: This study suggests that d3-GHR may protect AO-GHD particularly when treated with rhGH from the risk of VFs.

4(α-L-RHAMNOSYLOXY)-BENZYL ISOTHIOCYANATE, A BIOACTIVE PHYTOCHEMICAL THAT DEFENDS CEREBRAL TISSUE AND PREVENTS SEVERE DAMAGE INDUCED BY FOCAL ISCHEMIA/REPERFUSION.

Natural compounds are a promising source to treat several pathologies. The present study shows the in vivo pharmacological beneficial effect of 4(α-L-rhamnosyloxy)-benzyl isothiocyanate (glucomoringin isothiocyanate; GMG-ITC) obtained from glucomoringin (GMG; 4(α;-L-rhamnosyloxy)- benzyl glucosinolate), purified from Moringa oleifera seeds and hydrolyzed by myrosinase enzyme (β-thioglucoside glucohydrolase; E.C. 3.2.1.147). Cerebral ischemia/reperfusion (CIR) was induced in rats according to a classic model of carotid artery occlusion for a time period of 1 h and the reperfusion time was prolonged for seven days. GMG-ITC (3.5 mg GMG/ml plus 30 µl enzyme/rat; one ml i.p./rat) was administered 15 min after the beginning of ischemia and daily. The results clearly show that GMG-ITC possesses the capability to counteract the CIR-induced damage reducing TNF-alpha release, IκB-alpha cytosolic degradation/NFκBp65 nuclear translocation, as well as several other direct or indirect markers of inflammation (phospho-ERK p42/44, p-selectin) and oxidative stress (inducible Nitric Oxide Synthase (iNOS), MMP-9). GMG-ITC was shown to exert neuroprotective properties in preventing CIR-induced damage and the related cascade of inflammatory and oxidative mediators that exacerbate the progression of this disease in an experimental rat model. Our results clearly show that the tested phytochemical GMG-ITC possesses the capability to counteract CIR-induced damage.

Pituitary-tumour-transforming-gene 1 expression in testicular cancer.

Genomic instability is a feature of germ cell tumours. The pituitary-tumour-transforming-gene 1 (PTTG1) is the major effector of chromosome segregation during mitosis, protecting the cell from aneuploidy. The protein expression of this gene has been evaluated in testicular tumours by immunohistochemistry. Formalin-fixed and paraffin-embedded specimens of testicular tissues from 83 patients undergoing therapeutic orchidectomy for seminomas (n = 53), embryonal carcinoma (n = 10), yolk sac tumour (n = 10) and teratoma (n = 10) were examined. Seminoma was associated with in situ carcinoma (CIS) in 23 samples. PTTG1 immunostaining was performed using rabbit anti-PTTG1 as a primary antibody. In CIS, only isolated cells showed nuclear staining for PTTG1. In the peripheral area of seminoma, PTTG1 was mostly detected as localised in the nucleus; in the central area of seminoma, PTTG1 staining was more intense in cytoplasm. PTTG1-positive cells were also present in the areas of seminoma infiltration. On the other hand, in embryonal carcinoma, cells had a diffuse positive immunostaining, mainly cytoplasmatic, while we did not observe an expression of PTTG1 in yolk sac tumour and mature teratoma. We firstly identified the PTTG1 expression pattern in normal testis, CIS and testicular cancer. Further investigation is needed to clarify the functional activity of PTTG1 in testicular oncogenesis.

The treatment of neuroendocrine tumors with long-acting somatostatin analogs: a single center experience with lanreotide autogel.

The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lanreotide autogel given to metastatic well-differentiated (WD) neuroendocrine tumors (NET) patients observed in our Institute between 2005 and 2008. Patients with metastatic NET referred to our tertiary referral center were given lanreotide autogel 120 mg/month by deep sc injection for a period of at least 24 months. The efficacy was evaluated by the relief of disease symptoms, behavior of tumor markers and response rate in terms of time to tumor progression. Safety and tolerability were evaluated by assessing the onset of adverse events and treatment feasibility. Twenty-three patients (13 males), median age 62 yr (range 32-87) were considered for the study. All patients were affected by WD metastatic NET and had tumor progression in the last 6 months before the enrolment in the study. Median duration of response was 28 months (range 6-50 months). Fourteen patients (60.9%) showed flushing and diarrhea which improved by 85.7% and 55.6%, respectively, bronchoconstrinction and abdominal pain also ameliorated. A complete, partial or no-changed response in the tumor markers behavior was observed, respectively, in 42.9%, 22.9%, and 17.1% of cases. According to RECIST (Response Evaluation Criteria In Solid Tumors) criteria (version 1.1), there were 2 partial regression (8.7%) and 15 stable disease (65.3%); 6 patients (26.0%) progressed. No patient complained from any severe adverse reaction. The results of our study suggest that lanreotide autogel is effective in the symptoms, biochemical markers, and tumor progression control of WD metastatic NET and confirm that the treatment is well tolerated.

[Role of a mini-invasive approach in the diagnosis and treatment of tubo-peritoneal infertility as an altenative to IVF]. / Il ruolo di un approccio chirurgico mini-invasivo nello diagnosi e trattamento della sterilità tubo-peritoneale in alternativa alla FIVET.

AIM: Tubal factor infertility accounts for approximately 25-35% of cases of female infertility. Identifiable causes of tubal infertility are postinfectious tubal damage, postsurgical adhesion formation, and endometriosis-related adhesions. Aim of this study was to evaluate the results of a diagnostic/therapeutic minimally invasive approach in patients with suspect or ascertained mechanical infertility in terms of obtained pregnancies. METHODS: The study enrolled 143 patients who underwent diagnostic or operative laparoscopy, with chromopertubation, peritoneal or endometrial culture, salpingoscopy when indicated and diagnostic or operative hysteroscopy. Nine patients with submucous-intramural or multiple intramural fibroids underwent miomectomy by minilaparotomy following hysteroscopy and chromopertubation. Patients were contacted periodically by telephone to monitor the onset and outcome of pregnancy. The mean length of follow- up was 49 months (range: 11 to 118 months). RESULTS: Of the 152 patients considered in the study, 61 became pregnant (40%). Twenty-three pregnancies resulted in miscarriage, two in tubal pregnancy and one patient aborted after a diagnosis of Down syndrome. In total, 32% of the patients achieved a term pregnancy. CONCLUSION: The diagnostic/therapeutic mini-invasive approach allows women to become pregnant naturally and it is, therefore, an option for couples with ethical and religious concerns. The percentage of pregnancies is higher than after in-vitro fertilization. When efficacious, this approach allows additional spontaneous conceptions without renewed therapy and the course of pregnancy and the type of delivery will not differ from those in a normal population.

Statistical investigation about spinal clinical asymmetry in a school population.

BACKGROUND: Spinal disorders and obesity are increasing and are an important cause for concern among healthcare and educational bodies. There is a wide variability in the literature of clinical positivity for scoliosis in the examination of the spine. AIM: Our study aims to investigate a relationship between scoliosis hump in schoolchildren and obesity, evaluating different kind of variables. METHODS: The sample was comprised by 478 schoolchildren from Italy, with a mean age of 12.6 years (SD: 1.861). They were classified by using ATR test, body mass index (BMI), the Edinburgh Inventory, the deep flexion test. RESULTS: Results of ATR test evidence 26 subjects (5,4%) positive for ATR ≥ 7; 102 subjects (21,3%) positive for ATR ≥ 6; and finally 191 subjects (40,0%) positive for ATR ≥ 5. There were 191 (40%) subjects with scoliosis; obesity was present in 62 (13%) cases and, after the regression, associations were found between scoliotic posture and gender, presence of obesity, and flexibility. CONCLUSIONS: Our study confirms a relationship between obesity and scoliosis, which increases with the age. Female subjects have higher risks to develop humps and spinal disorders. It is advisable to use a combination of several parameters to achieve a more sensitive evaluation.

The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.

Ubiquitin Proteasome System (UPS) is an adaptable and finely tuned system that sustains proteostasis network under a large variety of physiopathological conditions. Its dysregulation is often associated with the onset and progression of human diseases; hence, UPS modulation has emerged as a promising new avenue for the development of treatments of several relevant pathologies, such as cancer and neurodegeneration. The clinical interest in proteasome inhibition has considerably increased after the FDA approval in 2003 of bortezomib for relapsed/refractory multiple myeloma, which is now used in the front-line setting. Thereafter, two other proteasome inhibitors (carfilzomib and ixazomib), designed to overcome resistance to bortezomib, have been approved for treatment-experienced patients, and a variety of novel inhibitors are currently under preclinical and clinical investigation not only for haematological malignancies but also for solid tumours. However, since UPS collapse leads to toxic misfolded proteins accumulation, proteasome is attracting even more interest as a target for the care of neurodegenerative diseases, which are sustained by UPS impairment. Thus, conceptually, proteasome activation represents an innovative and largely unexplored target for drug development. According to a multidisciplinary approach, spanning from chemistry, biochemistry, molecular biology to pharmacology, this review will summarize the most recent available literature regarding different aspects of proteasome biology, focusing on structure, function and regulation of proteasome in physiological and pathological processes, mostly cancer and neurodegenerative diseases, connecting biochemical features and clinical studies of proteasome targeting drugs.

Endogenous and artificial miRNAs explore a rich variety of conformations: a potential relationship between secondary structure and biological functionality.

Mature microRNAs are short non-coding RNA sequences which upon incorporation into the RISC ribonucleoprotein complex, play a crucial role in regulation of gene expression. However, miRNAs can exist within the cell also as free molecules fulfilling their biological activity. Therefore, it is emerging that in addition to sequence even the structure adopted by mature miRNAs might play an important role to reach the target. Indeed, we analysed by several spectroscopic techniques the secondary structures of two artificial miRNAs selected by computational tool (miR-Synth) as best candidates to silence c-MET and EGFR genes and of two endogenous miRNAs (miR-15a and miR-15b) having the same seed region, but different biological activity. Our results demonstrate that both endogenous and artificial miRNAs can arrange in several 3D-structures which affect their activity and selectivity toward the targets.

Ubiquitin binds the amyloid ß peptide and interferes with its clearance pathways.

Several lines of evidence point to a compromised proteostasis associated with a reduction of the Ubiquitin Proteasome System (UPS) activity in patients affected by Alzheimer's Disease (AD) and suggest that the amyloid ß peptide (Aß) is an important player in the game. Inspired also by many reports, underlining the presence of ubiquitin (Ub) in the amyloid plaques of AD brains, here we set out to test whether Ub may bind the Aß peptide and have any effect on its clearance pathways. By using an integrated array of MALDI-TOF/UPLC-HRMS, fluorescence, NMR, SPR, Microscale Thermophoresis (MST) and molecular dynamics studies, we consistently demonstrated that Aß40 binds Ub with a 1 : 1 stoichiometry and K d in the high micromolar range. In particular, we show that the N-terminal domain of the Aß peptide (through residues D1, E3 and R5) interacts with the C-terminal tail of Ub (involving residues K63 and E64), inducing the central region of Aß (14HQKLVFFAEDVGSNK28) to adopt a mixed α-helix/ß-turn structure. ELISA assays, carried out in neuroblastoma cell lysates, suggest that Aß competitively binds Ub also in the presence of the entire pool of cytosolic Ub binding proteins. Ub-bound Aß has a lower tendency to aggregate into amyloid-like fibrils and is more slowly degraded by the Insulin Degrading Enzyme (IDE). Finally, we observe that the water soluble fragment Aß1-16 significantly inhibits Ub chain growth reactions. These results evidence how the non-covalent interaction between Aß peptides and Ub may have relevant effects on the regulation of the upstream events of the UPS and pave the way to future in vivo studies addressing the role played by Aß peptide in the malfunction of proteome maintenance occurring in AD.

Prevalence of morphometric vertebral fractures in "difficult" patients with acromegaly with different biochemical outcomes after multimodal treatment.

INTRODUCTION: Skeletal fragility with high risk of vertebral fractures is an emerging complication of acromegaly in close relationship with duration of active disease. The aim of this cross-sectional study was to evaluate the prevalence and determinants of vertebral fractures in males and females with a history of long-standing active acromegaly undergoing treatment with Pegvisomant. SUBJECTS AND METHODS: Thirty-eight patients (25 females, 13 males) with acromegaly under Pegvisomant therapy were evaluated for vertebral fractures and bone mineral density at lumbar spine and femoral neck. Gonadal status, serum IGF1 levels and growth hormone receptor genotype were also assessed. RESULTS: Vertebral fractures were detected in 12 patients (31.6%). Fractured patients had longer duration of active disease (p = 0.01) with higher frequency of active acromegaly (p = 0.04), received higher dose of Pegvisomant (p = 0.008), and were more frequently hypogonadic (p = 0.02) as compared to patients who did not fracture. Stratifying the patients for gender, vertebral fractures were significantly associated with Pegvisomant dose (p = 0.02) and untreated hypogonadism (p = 0.02) in males and with activity of disease (p = 0.03), serum insulin-like growth factor-I values (p = 0.01) and d3GHR polymorphism (p = 0.005) in females. No significant association was found between vertebral fractures and bone mineral density at either skeletal site. CONCLUSION: Vertebral fractures are a frequent complication of long-standing active acromegaly. When patients are treated with Pegvisomant, vertebral fractures may occur in close relationship with active acromegaly and coexistent untreated hypogonadism.

Effects of ghrelin administration on endocrine and metabolic parameters in obese women with polycystic ovary syndrome.

INTRODUCTION: The novel peptide ghrelin displays multiple endocrine and non-endocrine actions. Its strong GH-releasing activity in humans has long been recognized. However, in obesity, ghrelin administration induces a blunted GH secretion, enhances glucose and reduces insulin levels. The effects of ghrelin administration have not been investigated in polycystic ovary syndrome (PCOS), which can be associated with obesity, hyperinsulinism, and GH hyposecretion. Leptin is a mediator for energy balance opposed to ghrelin; both of them are supposed to act as regulators of reproductive functions. AIM OF THE STUDY: Evaluate the endocrine and metabolic response to ghrelin administration in PCOS obese patients compared to body mass index (BMI)-matched and normal weight women. MATERIALS AND METHODS: Nine obese PCOS patients (BMI: 35.4+/-1.2 kg/m(2)) (OB PCOS), 6 obese controls (BMI: 38.4+/-1.1 kg/m(2)) (Ob), and 6 normal-weight women (BMI: 23+/-0.6 kg/m(2)) (NW) were enrolled in the study. In all patients we performed: 1) basal hormonal evaluation including FSH, LH, estradiol, testosterone, androstenedione, DHEAS, SHBG, 17-hydroxyprogesterone (17OHP), IGF-I, free T3 (FT3), free T4 (FT4) and ghrelin levels; 2) metabolic evaluation as follows: concentration of non-esterified fatty acid (NEFA) and oral glucose tolerance test (OGTT) (75 g); homeostasis model assessment (HOMA); glucose and insulin response to ghrelin administration (1 microg/kg); 3) measurement of GH, PRL, TSH, and leptin levels after infusion of ghrelin. RESULTS: Administration of ghrelin increased glucose and reduced insulin levels in both Ob and OB PCOS. Moreover, ghrelin enhanced GH and PRL levels in all groups but it did not modify TSH and leptin levels. GH peak and area under the curve (AUC) in OB PCOS and Ob were lower than controls (p<0.05). Similar PRL peak and AUC values were observed in all groups. CONCLUSIONS: In both obese and PCOS obese patients, leptin levels are not influenced by ghrelin administration. Moreover, the GH response after ghrelin administration is blunted. However, ghrelin exerts glucose- enhancing and insulin-lowering effects, the latter absent in NW.

Experimental strain analysis on the entire bony leg compared with FE analysis.

The present study addresses the question of evaluating, by combining both experimental and numerical approaches, the stress/strain distribution within a complete model of the entire lower bony chain. With this purpose an experimental model and a complete 3D finite element one were realised. A load of 700 N has been applied at the top of pelvis and the feet were rigidly fixed. Obtained results reveal interesting consequences deriving by taking into account the complete bony chain; it is possible to get information on load sharing between bones, location of high strain concentrations, and bone relative motion.

Prednisone treatment in infertile patients with oligozoospermia and accessory gland inflammatory alterations.

The association between inflammation of the male reproductive system and oligozoospermia has been frequently reported in the clinical work-up of male infertility. To improve sperm parameters in infertile patients with genital inflammation, many phytochemical and nutraceutical drugs are currently being used. However, their use is still empirical and no conclusive data have been provided about their efficacy. The treatment with steroid anti-inflammatory drugs might be useful in reducing inflammation and improving sperm parameters, thus increasing the fertility outcome. The aim of this study was to evaluate if glucocorticoid treatment improves seminal parameters in infertile oligozoospermic patients presenting signs of accessory gland inflammation at genital ultrasound. A total of 90 infertile patients were enrolled in the study. They presented normal testicular volume, normal FSH plasma levels, the presence of various degrees of oligozoospermia, associated with scrotal and trans-rectal ultrasound signs indicative of accessory gland inflammation, but negative microbiological analysis on semen and/or prostatic secretions. Patients were randomly allocated into three groups of treatment, receiving, respectively, 5, 12.5, and 25 mg daily oral Prednisone for one month. Seminal parameters were evaluated at admission and after treatment. In patients undergoing Prednisone treatment at a daily dose of 5 mg we observed a significant increase in total sperm count. At a daily dose of 12.5 mg, Prednisone treatment improved sperm concentration, total sperm count, and the percentage of sperm motility. Twenty-five mg of Prednisone led to significant improvement in all the sperm parameters, except for semen volume. These results clearly demonstrate that Prednisone treatment can significantly improve sperm parameters in a selected population of oligozoospermic patients. These findings suggest that Prednisone treatment should be considered in idiopathic oligozoospermic patients with supposed normal spermatogenesis and accessory gland inflammatory alterations, in order to improve sperm parameters and fertility outcome.

Inter-hemispheric Claustral Connections in Human Brain: A Constrained Spherical Deconvolution-Based Study.

PURPOSE: Complex claustral connection network was widely demonstrated both in humans and animals. Moreover, several studies have suggested that claustral connections directly involve also the contralateral hemisphere. Detection of contralateral cortico-claustral and inter-claustral connections was reported mainly in animals and only partially in humans. The main purpose of this study was to provide more robust tractography-driven support of the existence of inter-hemispheric claustral connections in humans, by means of a dedicated optimized tractographic protocol. METHODS: Fifteen healthy subjects were examined by means of an advanced magnetic resonance imaging-based probabilistic constrained spherical deconvolution tractographic protocol. Moreover, quantitative diffusion parameters were extracted by each reconstructed pathway. RESULTS: In this study, further imaging-based support on the possible existence in humans of contralateral cortico-claustral and inter-claustral connections was provided. These connections were found to involve almost all the superior portion of each claustrum, showing a topographical organization. Moreover, the detection of inter-claustral connections passing through the anterior commissure was reported, for the first time, in humans. CONCLUSIONS: The possible existence of inter-claustral and cortico-claustral contralateral pathways might provide the morphological basis for the complex functional phenomena observed in previous studies. Furthermore, these connections might have several important clinical implications, since they might explain how the inter-hemispheric coordination governed by the claustrum, as well as the functional recovery subsequent to damages involving one claustrum, takes place.

Second generation ultrasonographic contrast agents in the diagnosis of neoplastic thyroid nodules.

To verify whether the use of second generation ultrasonographic contrast agents leads to an improvement in the differential diagnosis of thyroid nodules, twenty patients, eligible for uninodular goiter surgery were studied. All patients previously underwent complete hormonal profile, bidimensional thyroid ultrasonographic, Colour Doppler evaluation and 99 mTc scintiscan. All nodules were as well evaluated before and after sulphur-hexafluoride administration. Wash-in time, contrast agent intra-nodular flow and wash-out time were evaluated. These data were compared with the cytology and histology findings. On the basis of the histological examination we divided our study population in 2 groups: in the group of neoplastic lesions (4 follicular adenomas and 6 carcinomas) an early wash-in was observed, with an homogeneous peripheral pattern enhancement, a rapid centripetal progression and an extended persistence of the contrast agent inside the nodule. In 6 out of 10 cases of thyroid neoplasia a fast wash-out was observed. In the group of benign lesions, in the patients affected by nodular goiter, an intra-nodular perfusion as opposite to the healthy surrounding parenchyma was observed. Even though ultrasound contrast agent technique has a limited invasivity and is more expensive than Fine Niddle Aspiration (FNA), the preliminary data of this pilot study suggest that this method might prove useful, to differentiate benign from malignant thyroid nodules.

Increased estradiol levels in venous occlusive disorder: a possible functional mechanism of venous leakage.

Venous insufficiency of the corpora cavernosa is the second most common cause of erectile dysfunction (ED). A functional insufficiency of the venous system has been hypothesised, but the cause is still unclear. To evaluate a possible endocrine mechanism, we have studied hormone profile in a group of nine patients with pure venous-leakage (VL) compared with a control group of 15 patients with ED of different origin. Prolactin, testosterone and gonadotropin levels did not differ among the two groups, while estradiol (E2) plasma concentration was significantly higher in VL patients compared to controls. Our data support the hypothesis that the steroid environment, in particular estradiol level, can influence venous vascular tone (via VEGF or NO), thus affecting venous leakage dysfunction. This point can explain a possible link between the high estradiol levels and a functional insufficiency of the venous system in ED.

The insulin degrading enzyme activates ubiquitin and promotes the formation of K48 and K63 diubiquitin.

We report an ATP-dependent ubiquitin conjugation with IDE which, in turn, promotes Ub-Ub linkages in tube tests. We propose a novel function for IDE as a non-canonical ubiquitin activating enzyme.