Acid Derivatives of Pyrazolo[1,5-a]pyrimidine as Aldose Reductase Differential Inhibitors

Aldose reductase (AKR1B1), the key enzyme of the polyol pathway, plays a crucial role in the development of long-term complications affecting diabetic patients. Nevertheless, the expedience of inhibiting this enzyme to treat diabetic complications has failed, due to the emergence of side effects from compounds under development. Actually AKR1B1 is a Janus-faced enzyme which, besides ruling the polyol pathway, takes part in the antioxidant defense mechanismof the body. In this workwe report the evidence that a class of compounds, characterized by a pyrazolo[1,5-a]pyrimidine core and an ionizable fragment, modulates differently the catalytic activity of the enzyme, depending on the presence of specific substrates such as sugar, toxic aldehydes, and glutathione conjugates of toxic aldehydes. The study stands out as a systematic attempt to generate aldose reductase differential inhibitors (ARDIs) intended to target long-term diabetic complications while leaving unaltered the detoxifying role of the enzyme

The Italian National Register of infants with congenital hypothyroidism: twenty years of surveillance and study of congenital hypothyroidism

All the Italian Centres in charge of screening, diagnosis, and follow-up of infants with congenital hypothyroidism participate in the Italian National Registry of affected infants, which performs the nationwide surveillance of the disease. It was established in 1987 as a program of the Health Ministry and is coordinated by the Istituto Superiore di Sanità. The early diagnosis performed by the nationwide newborn screening programme, the prompt treatment and the appropriate clinical management of the patients carried out by the Follow-up Centres, and the surveillance of the disease performed by the National Register of infants with congenital hypothyroidism are the components of an integrated approach to the disease which has been successfully established in our country

Postoperative peripheral neuropathies associated with patient positioning during robot-assisted laparoscopic radical prostatectomy (RARP): A systematic review of the literature

Objective: To perform a systematic review of the literature concerning postoperative peripheral neuropathies associated with patient positioning during robot-assisted laparoscopic radical prostatectomy (RARP)

Determinazione degli elementi minerali in pesci marini allevati nel Nord Adriatico.

This study aimed at evaluating mineral elements content in two reared species of marine fish. Flesh samples of shi drum (Umbrina cirrosa) from ponds and off-shore European sea bass (Dicentrarchus labrax) were analysed by PIXE (Particle Induced X-Ray Emission) technique. Regarding both species, results showed a high nutritional value and a large variation intra-species probably due to genetic differences. theamount of heavy metals (Pb and Hg <0.1 ppm9 and metalloids (As <1 ppm) were lower than those detected in the same wild fish species. Thus, environmental and feeding condition did not affect food security

Surgical and functional outcomes after robot-assisted radical cystectomy in female patients: a systematic review of the literature

Aim: We aimed to review and summarize recent data on surgical and functional outcomes in women undergoing robot-assisted radical cystectomy (RARC) and urinary diversion (UD) for bladder cancer, compared with male and open counterparts.Methods: A systematic review of English-language articles published in the last 15 years was performed on PubMed/Medline database according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Outcomes of interest included peri- and post-operative surgical outcomes [operative time (OT), estimated blood loss (EBL), hospital stay (LOS), complications, and readmission], pathological outcomes [pT stage, lymph node (LN) yield, positive surgical margins (PSMs), and positive LN (pN+)], and functional outcomes [daytime and nighttime continence, sexual activity, need for clean intermittent catheterization (CIC), and quality of life (QoL) evaluation].Results: Overall, eight studies were selected collecting data from 229 female patients undergoing RARC. The median OT was 418 min (range 311-562 min) and the median EBL was 380 mL (range 100-1160 mL). OT and EBL were not significantly different comparing males and females, whereas the robotic approach was found to be significantly related with longer OT and lower EBL compared to the open procedure. The median LOS was 9.8 days (range 6.5-21 days); no significant differences in LOS were found between open RC (ORC) and RARC in female patients, as well as between RARC in women and men. The mean incidence of 30-day complications after RARC in women was 32.9%, with 12% of high-grade complications, while the 30- and 90-day readmission rates were 20.8%, and 28%, respectively. Complications and readmission comparing RARC and ORC in female patients appear to be overlapping. The mean rate of PSMs was 2.5% and the mean rate of pN+ was 12.7%; both these outcomes were similar in RARC compared with ORC. The mean number of retrieved LN was 20.6 (range 11.3-35.5). The LN yield resulted significantly influenced by the robotic approach [median 27 (range 19-41)] compared to the open one [20.5 (range 13-28)]. After 12 months, the rate of women with daytime and nighttime continence was 66.7%-90.9% and 66.7%-86.4%, respectively, while that of sexually active women ranged 66.7%-72.7%. The need for CIC ranged 12.5%-27.2%. Administering the EORTC-QLQ-C30 questionnaire after RARC and intracorporeal neobladder, the global health status/QoL and physical and emotional functioning items improved significantly over time.Conclusion: RARC and UD in female patients is a feasible procedure with surgical outcomes overlapping with those in the male patient population. Postoperative functional outcomes on continence, sexual function, and QoL are still poorly investigated, although results inherent in the nerve-sparing approach appear promising

Il rapporto tra etica, scienza, tecnologia nella ricerca, nel lavoro, nella società. Ricerca in ottica di genere.

Troppo spesso si parla di etica, di tecnologie e del rapporto tra queste scienze e i/le giovani. Ma le cose stanno così come viene detto? per rispondere a questa domanda e per conoscere un po' meglio il punto di vista delle/dei giovani e le differenze tra i sessi, è stata svolta una ricerca su 400 studenti che ha dato risultati sorprendenti

Silodosin and tadalafil have synergistic inhibitory effects on nerve-mediated contractions of human and rat isolated prostates.

Lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) are associated with erectile dysfunction. Alpha-1-adrenoceptor antagonists are effective drugs for treating symptomatic BPH. Clinical data show improvements in LUTS by phosphodiesterase 5 inhibitors. This study aimed to evaluate effects of silodosin, a highly selective α1A-adrenoceptor antagonist, alone or in combination with the phosphodiesterase 5 inhibitor tadalafil on contractions of isolated human and rat prostates. In organbath studies, effects of increasing concentrations of silodosin (1nM-1µM) and tadalafil (100nM-100µM) on contractions by electrical field stimulation or phenylephrine of human and rat prostate strip preparations were investigated. The combination silodosin and tadalafil reduced electrically-induced contractions of human prostate preparations better than single drugs alone. At any frequencies (1-32Hz), inhibitory effects of combined therapy (P-values vs single drug) in human tissue were 26-42% (1nM silodosin+100nM tadalafil; P<0.05), 40-58% (10nM silodosin+1µM tadalafil; P<0.001-0.05), 56-67% (100nM silodosin+10µM tadalafil; P<0.01-0.05), and 33-55% (1µM silodosin+100µM tadalafil P<0.01-0.05). Similar findings were obtained in rat prostate preparations. In human and rat prostate tissue, the drug combination exerted similar inhibitory effect on phenylephrine contractions as silodosin alone. Silodosin plus tadalafil had greater potency than each drug alone to inhibit prostate contractions to electrical field stimulation but not to phenylephrine. This study supports the clinical application of a combination of an α1A-adrenoceptor antagonist and a phosphodiesterase 5 inhibitor for symptomatic BPH and suggests that the drug combination requires endogenous nerve-activity for optimal effect

Testosterone Levels Correlate With Grade Group 5 Prostate Cancer: Another Step Toward Personalized Medicine

BACKGROUND: Controversial results have shown a significant association with either low or high total testosterone (tT) levels and high risk prostate cancer (PCa). We tested the relationship between circulating tT and grade group 5 (G5) PCa at radical prostatectomy (RP) in patients with preoperative low- to intermediate-risk disease. METHODS: Serum sex hormones were assessed the day before RP in a cohort of 846 patients with low- to intermediate-risk PCa. Patients were segregated using the new 5-tiered Gleason grade groups. Restricted cubic spline functions and logistic regression analyses tested the association between sex hormones and G5 PCa. Differences in potential predictive accuracy (PA) were assessed for tT and prostate-specific antigen (PSA) levels. RESULTS: Overall, 27 men (3.2%) had G5 PCa at RP, and this group had higher PSA values than patients with G1–G4 PCa (P = 0.02). The groups did not differ in terms of preoperative mean hormonal values. Both low and high circulating tT values depicted a nonlinear U-shaped correlation with G5 PCa at RP. The lowest and highest (10th and 90th percentiles) tT values and biopsy PCa grade emerged as multivariable independent predictors of G5 PCa at RP (all P &lt; 0.05). PA for G5 PCa did not differ between tT (area under the curve [AUC] 0.631) and PSA (AUC 0.636). CONCLUSIONS: Circulating tT was a significant predictor of G5 PCa at RP in patients with preoperative low- to intermediate-risk disease. Preoperative tT and PSA values showed similar PA for the most aggressive disease, confirming a potential role for circulating androgens in preoperative risk assessment of PCa patients. Prostate 77:234–241, 2017