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Biomedical subjects

S Gabriele

Publications and source records attributed to S Gabriele.

At least 19 recordsLinked to original sources

Xenoestrogens and the induction of proliferative effects in breast cancer cells via direct activation of oestrogen receptor alpha.

Environmental contamination with a variety of industrial products has been associated with developmental and reproductive abnormalities in wildlife species. Increasing evidence has suggested that bisphenol A (BPA) and 4-nonylphenol (NPH), two major endocrine-disrupting chemicals, might be responsible for adverse effects on humans as a consequence of ubiquitous use together with potential oestrogen-like activity. To provide insight into the oestrogen-like nature of BPA and NPH, their ability to activate a reporter gene construct via an oestrogen response element in the hormone-dependent breast cancer cell lines MCF7 and T47D was ascertained. Both compounds transactivated the endogenous oestrogen receptor (ER) alpha in a direct fashion since the anti-oestrogen 4-hydroxytamoxifen abolished the response. In addition, using steroid-receptor-negative HeLa cells engineered to express ERalpha and ERbeta and the hormone-binding domains of both ERalpha and ERbeta, BPA and NPH confirmed the direct transcriptional activity. Interestingly these properties were supported in MCF7 cells by the ability to autoregulate ERalpha expression as well as to induce its nuclear compartmentalization. We therefore evaluated by reverse transcriptase polymerase chain reaction the expression of oestrogen-controlled genes such as cathepsin D and TFF1 (formerly pS2), which were increased by both chemicals tested. The agonistic effects exhibited in all assays performed prompted the evaluation of a more complex biological response such as the proliferation of MCF7 and T47D cells. The same concentration of xenoestrogens eliciting substantial transcriptional activity significantly stimulated the proliferation of both breast cancer cell lines, although with a reduced effectiveness with respect to the natural hormone 17beta-oestradiol. The results indicate that the biological action of environmental oestrogen such as BPA and NPH should be taken into account for the potential impact on human disease-like hormone-dependent breast cancer. However, further studies are needed to clarify their bioavailability and metabolism as well as whether compound mixtures could produce noticeable effects by synergistic activity.

Benzhydryl Compounds↗

Emerging potentials for an antioxidant therapy as a new approach to the treatment of systemic sclerosis.

Oxidative stress, favoring disease progression by a rapid degeneration of endothelial cell function is deeply involved in Systemic Sclerosis (SSc) pathogenesis. Raynaud's phenomenon (RP), present in 90% of patients with SSc, provoking frequent daily episodes of hypoxia-reperfusion injury, produces several episodes of free radicals-mediated endothelial derangement. These events results in a positive feedback effect of luminal narrowing and ischemia and therefore to the birth of a vicious cycle of oxygen free radicals (OFR) generation, leading to endothelial damage, intimal thickening and fibrosis. Thus ischemia and reperfusion are two criticals events that may induce oxidative stress and inactivation of antioxidant enzymes. In RP and SSc, a reduced concentration of ascorbic acid, alpha-tocopherol and beta-carotene as well as low values of Selenium have been reported. This antioxidative potential deficiency increases the propensity to oxidative stress. favoring the development of injury mediated by OFR. We reviewed several antioxidant compounds, aiming at their capacity of reverting endothelial dysfunction and damage, scavenging lipid peroxidation and reducing multiple episodes of hypoxia-reperfusion injury. In order to interrupt SSc vicious cycle, we propose a main strategy for SSc treatment by a supplementation of antioxidants and different kind of drugs with antioxidant property, such as Lazaroids, Resveratrol, Melatonin and Probucol.

Antioxidants↗

Retinoic acid stimulates plasminogen activator inhibitor 2 production by blood mononuclear cells and inhibits urokinase-induced extracellular proteolysis.

Retinoids have been shown to modulate several functions of mononuclear phagocytes. We investigated the in vitro effect of all-trans-retinoic acid (ATRA) on the production of two major fibrinolytic components, urokinase-type plasminogen activator (u-PA) and PA inhibitor 2 (PAI-2), by human blood mononuclear cells (MNC). ATRA caused a dose-dependent (range 0.01-10 microM) accumulation of PAI-2 antigen and activity into the cell culture medium, with a maximal increase (about 5-fold over control) at a concentration of 1-10 microM. Similarly, a dose-dependent increase in PAI-2 antigen was observed in cell extracts upon ATRA stimulation. Northern blot analysis showed a parallel increase in the amount of PAI-2 mRNA in ATRA-treated cells. Time-course experiments with 1 microM ATRA showed enhanced PAI-2 mRNA expression as early as 2 h, reaching a maximum at 4-6 h and then declining at 18-24 h, and a time-dependent increase in PAI-2 antigen in the cell culture medium. At variance with PAI-2, u-PA was not influenced by the drug. To establish whether ATRA-induced changes influenced the fibrinolytic process, we evaluated the effect of MNC stimulated with ATRA on u-PA-induced degradation of diluted plasma clots. ATRA-treated cells markedly inhibited clot lysis induced by low concentrations of u-PA. The effect was due to enhanced extracellular PAI-2 accumulation since it was observed with conditioned medium from ATRA-treated cells; it was abolished by the addition of neutralizing anti-PAI-2 antibodies and was negligible when single-chain t-PA was used instead of u-PA. Since monocyte/macrophage-mediated, plasminogen-dependent extracellular proteolysis has been proposed as an important mechanism of tissue damage in several inflammatory states, our findings might contribute to better explain the anti-inflammatory properties of retinoids.

Blotting, Northern↗

The relationship of cognitive, personality, and academic measures to anesthesiology resident clinical performance.

UNLABELLED: Cognitive skills (including vigilance), personality factors, and standardized academic test performance may be associated with clinical competence in anesthesiology to varying degrees. Sixty-seven anesthesiology residents in training at one center between 1993 and 1995 were administered the modified Vigil (For Thought, Ltd., Nashua, NH), the Paced Auditory Serial Addition Test, the California Personality Inventory, the State-Trait Anxiety Inventory, and five standardized academic performance tests. The clinical performance of anesthesiology residents was rated on a quarterly basis by a clinical competence committee. A growth curve model indicated that there was significant variability in clinical competence at the start of residency and a statistically significant improvement over time, and that the relative ranking of the residents remained stable over the course of training. Of 46 potential variables, 7 were associated (P < 0.10) with poor clinical performance; these were subjected to a multivariate test (Mantel-Haenszel). Cognitive variables predicting poor clinical performance were difficulty performing a rapid mental arithmetic test requiring divided attention and commission errors during complex visual target detection. Personality variables predicting poor clinical performance were introversion and flexibility. A predictive academic variable was poor anesthesia knowledge as measured by using two different tests during the first month of training. There were varying levels of independence among these variables. IMPLICATIONS: Early academic test performance and certain cognitive and personality tests were associated with the clinical performance of anesthesiology residents. The predictive value of these findings should be confirmed in a prospective, multicenter study.

Anesthesiology↗

Endoscopic treatment of vesicoureteral reflux prior to renal transplantation.

Endoscopic subureteral injection of Teflon was done in 34 potential renal transplant recipients to correct vesicoureteral reflux. Follow-up ranged from 6 to 24 months. After one injection reflux was corrected in 53.7% of the patients; this increased to 64.8% after a second injection. The procedure is simple, effective, without major morbidity, and avoids the risk of nephroureterectomy. However, efforts must be made to find an ideal substance with a higher biocompatibility and without risk of migration.

Adult↗

[Long term results of endoscopic treatment of reflux in hemodialysis patients waiting for transplantation].

Between January 1986 and April 1988, 13 patients (mean age: 35 years) waiting for renal transplantation (mean duration of haemodialysis: 46 months) were treated by means of O'Donnell's technique. Vesico-ureteric reflux was unilateral in 6 patients and bilateral in 7 patients (20 refluxing ureteric units). Reflux was classified as Grade II for 7 ureters, Grade III for 8 ureters and Grade IV for 5 ureters. The volume of Teflon injected ranged from 1 to 4 cm3 and 6 patients received repeated injections. No complications were observed. Complete resolution of reflux was obtained in 9 patients (69%), i.e. 15 ureteric units (75%). Reflux persisted in 4 patients (31%), i.e. 5 ureteric units (25%). Three nephro-ureterectomies were performed in 2 patients with persistent high grade reflux, but 2 patients with Grade I reflux after endoscopic treatment were not operated. All patients were transplanted after endoscopic treatment (mean interval between correction of reflux and transplantation: 13 months) and a follow-up cystography was systematically performed after transplantation (mean follow-up after transplantation: 27 months): no recurrence of the reflux was detected (mean follow-up after endoscopic treatment: 40 months). Endoscopic treatment of reflux avoids the need for nephro-ureterectomy in 80% of haemodialysis patients waiting for renal transplantation and presenting with vesico-ureteric reflux.

Administration, Intravesical↗

[Correction of posterior hypospadias by a transverse vascular preputial graft, evolution of technics and results. Apropos of 42 cases].

During more than seven years 42 hypospadias were treated in on stage with different technics of urethroplasty by transverse preputial gauntlet grafts. With original Duckett's technic only 21,5% of patients had a good result. The authors reduced the risk of devascularisation first time by a personal modification then by using the double face flap described by Duckett himself; then the percentage of success after one operation overtake 75%. The different complications and their treatment are described and some operative details are pointed out to prevent complications.

Adolescent↗

[Treatment of vesico-ureteral reflux in children by endoscopic injection of teflon. Evaluation of 2 years' experience].

Authors treated 131 children with vesicoureteric reflux by endoscopic injection of teflon (217 ureters). At one month follow-up, 88.04% of cases were treated successfully after the first injection, 93.22% of these good results were effective one year later. A complete correction was obtained in 89.3% after one or two injections. Most of recurrence was attributed to insufficient amounts of Teflon and to difficult anatomical conditions. Indications of this procedure and safety of the paste used are discussed.

Adolescent↗

[Impact of a new cognitive remediation strategy on interpersonal problem solving skills and social autonomy in schizophrenia].

INTRODUCTION: Despite recent developments, the impact of pharmacotherapy on social autonomy and interpersonal problem solving skills in patients with schizophrenia remains limited, with consequences in terms of socio-professional functioning. Indeed, independently of the positive, negative and/or disorganization symptoms, functional deficits in patients with schizophrenia rely mainly on various cognitive impairments. OBJECTIVES: To determine the impact of a new Cognitive Remediation Strategy on interpersonal problem solving skills, social autonomy and symptoms in patients with schizophrenia. METHODS: Thirty patients with schizophrenia were enrolled in a program consisting of 14 training sessions of 4 cognitive functions (attention/concentration, topological memory, logical reasoning, executive functions) using the REHACOM software. Measurements of attention (Continuous Performance Test, CPT), memory (Rivermead Behavioural Memory Test, RBMT) and executive functions (Wisconsin Card Sorting Test, WCST) as well as interpersonal problem solving skills (Assessment of Interpersonal Problem-Solving Skills, AIPSS) and social autonomy (Social Autonomy Scale, EAS) and finally schizophrenia symptoms (Positive And Negative Syndrom Scale, PANSS) were undertaken at the beginning and the end of the 14 remediation meetings. RESULTS: Cognitive functions, interpersonal problems solving skills, social autonomy and symptoms were significantly improved by the Cognitive Remediation Strategy. CONCLUSION: Our results confirm the therapeutic impact of a Cognitive Remediation Strategy among 30 schizophrenic patients stabilised on clinical, therapeutic and functional levels. The question of the long-term maintenance of such improvements still requires further investigation.

Adolescent↗

[Activities at the Rome Anti-Rabies Center in 2000: analysis and proposals].

The Authors analyzed data from the 1,817 patients (mean age 35.3 +/- 20.6, median 32) treated at the Antirabies Centre of Rome in the year 2000; of these 8.9% were immigrants. Dogs (84.1%) and cats (9.8%) were responsible for most bites. Stray animals were 39.9%, with an owner 58.3% and those without data 1.8%. Over 1/3 of patients could not refer the cause of bite. Most patients (93.0%) went first to hospital, where tetanus prophylaxis was administered preferably by immunoglobulins (25.0%) instead of vaccine (6.6%). Antirabies vaccine (HDCV and/or DEV) was prescribed to 777 patients (42.8%) and administered to 642 (35.3%), but only 296 (16.3%) of them received at least 5 doses. Veterinary observation always confirmed the absence of rabies in central Italy. Immunoglobulins were prescribed only to 14 patients. The data shown in this study emphasize the opportunity to differentiate the Italian antirabies protocol according to the geographic area.

Academic Medical Centers↗